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OpenTrials
Completed

NCT Number: NCT03481660

A Study of the Efficacy and Safety of Brolucizumab vs. Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema

This was a Phase III, randomized, double-masked, multi-center, active-controlled, two-arm study designed to evaluate the efficacy and safety of brolucizumab 6 mg compared to the active control, aflibercept 2 mg used per authorized label, in subjects with visual impairment due to diabetic macular edema (DME).

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Key information

Conditions

Diabetic Macular Edema

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Alken, Belgium

Loading trial locations.

About this study

The study included a screening period of up to 2 weeks to assess eligibility, followed by a double-masked treatment period (Day 1 to Week 96). The baseline visit was defined as Day 1/Visit 1, and end of treatment visit as Visit 27 (Week 96). After the last treatment visit, there was a post-treatment follow-up period from Week 96 to Week 100 and an exit visit at Week 100. Subjects were assigned to one of two treatment arms in a 1:1 ratio: brolucizumab 6 mg/0.05 mL (5 loading doses each administered every 6 weeks (q6w) during loading phase then q12w/q8w during maintenance phase with an option to extend treatment interval by 4 weeks during the second year) or aflibercept 2 mg/0.05 mL (5 loading doses each administered every 4 weeks (q4w) during loading phase then q8w during maintenance phase).

Disease activity assessments (DAAs) were conducted by the masked investigator for both treatment arms at Week 32 and Week 36, i.e., 8 and 12 weeks after the end of the loading phase for subjects receiving brolucizumab, and at Week 48, Week 60 and Week 72 (i.e., every 12 weeks). In the brolucizumab arm, subjects who qualified for q12w during this initial q12w interval continued on a q12w treatment frequency unless disease activity was identified at any of the subsequent DAA visits, in which case subjects were switched to a q8w treatment interval until Week 72.

A one-time disease stability assessment was performed by the masked investigator at Week 72 in both treatment arms with the purpose of evaluating the potential for treatment interval extension by 4 weeks. The subjects in the brolucizumab arm who demonstrated disease stability in the one-time assessment at Week 72 under their current assigned treatment regimen (q12w or q8w) were considered for treatment interval extension. To evaluate the adequacy of the individualized q8w, q12w or q16w treatment intervals in the brolucizumab arm, DAAs were performed at every visit from Week 72 up to and including Week 96 (i.e., every 4 weeks) and subjects had their treatment interval modified accordingly. If after Week 72 disease activity had been identified by the masked investigator at a scheduled treatment visit (according to the subject specific treatment schedule q12w or q16w) the subject was assigned to q8w treatment schedule.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

General

  • Patients must give written informed consent before any study related assessments are performed
  • Patients with type 1 or type 2 diabetes mellitus and HbA1c of =< 10% at screening
  • Medication for the management of diabetes must have been stable within 3 months prior to randomization and is expected to remain stable during the course of the study

Study Eye

  • Visual impairment due to DME with:
  • BCVA score between 78 and 23 letters, inclusive, using Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity testing charts at a testing distance of 4 meters (approximate Snellen equivalent of 20/32 to 20/320), at screening and baseline
  • DME involving the center of the macula, with central subfield retinal thickness (measured from RPE to ILM inclusively) of >= 320 micrometers (μm) on SD-OCT at screening If both eyes are eligible, the eye with the worse visual acuity will be selected for study eye. However, the investigator may select the eye with better visual acuity, based on medical reasons or local ethical requirements.

Key Exclusion Criteria:

  • Previous treatment with any anti-VEGF drugs or investigational drugs in the study eye
  • Active proliferative diabetic retinopathy in the study eye as per the investigator
  • Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g., cataract, vitreous hemorrhage, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization of any cause)
  • Any active intraocular or periocular infection or active intraocular inflammation (e.g., infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline
  • Structural damage of the fovea in the study eye at screening likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques
  • Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 millimeters mercury (mmHg) on medication or according to investigator's judgment, at screening or baseline
  • Neovascularization of the iris in the study eye at screening or baseline
  • Evidence of vitreomacular traction in the study eye at screening or baseline which, in the opinion of the investigator, affect visual acuity

Treatment and study plan

Brolucizumab

Drug

Intravitreal injection

Other names: RTH258, ESBA1008

aflibercept

Drug

Intravitreal injection

Other names: Eylea

Primary outcomes

  1. Mean Change From Baseline in Best-corrected Visual Acuity (BCVA) at Week 52 for the Study Eye

    Time frame: Baseline, Week 52

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

Secondary outcomes

  1. Average Mean Change From Baseline in BCVA Over the Period Week 40 Through Week 52 for the Study Eye

    Time frame: Baseline, period Week 40 through Week 52

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defined as the mean change from baseline to the average value over the period Week 40 through Week 52. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  2. (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 and up to q12w/q16w up to Week 100.

    Time frame: Week 52, Week 100

    The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen [every 12 weeks (q12w)].

  3. (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w up to Week 52 Within Those Patients That Qualified for q12w at Week 36

    Time frame: Week 36, Week 52

    The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen [every 12 weeks (q12w)].

  4. (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained at q12w/q16w up to Week 100, Within Those Patients That Qualified for q12w at Week 36

    Time frame: Week 36, Week 100

    Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension.

    The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen [every 12 weeks (q12w)].

  5. (Brolucizumab Treatment Arm Only): Percentage of Participants Maintained on q16w up to Week 100 Within the Patients on q12w at Week 68 and on q16w at Week 76

    Time frame: Week 68, Week 76, Week 100

    Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension.

    The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen [every 12 weeks (q12w)].

  6. (Brolucizumab Treatment Arm Only): Percentage of Participants Re-assigned and Maintained on q12w up to Week 100 Within the Patients on q8w at Week 68 and on q12w at Week 80

    Time frame: Week 68, Week 80, Week 100

    Disease activity assessments (DAAs) were performed to identify q8w-need at pre-specified visits (Weeks 32, 36, 48, 60, 72 and every visit from Week 72 through Week 96). Weeks 32 and 36 were the two DAA visits of the initial q12w cycle after the loading phase of the brolucizumab arm. At Week 72 or Week 76 (if DAA/disease stability assessment was missed at Week 72), participants in the brolucizumab were evaluated for an additional 4-week dose regimen extension.

    The number of participants maintaining every 12 weeks (q12w) treatment status in the Brolucizumab arm was derived based on Kaplan-Meier estimates time-to-first q8w treatment need. Positive treatment status was defined as intravitreal treatment (IVT) injections per planned dosing regimen [every 12 weeks (q12w)].

  7. (Brolucizumab Treatment Arm Only): Number of Participants With Injections Per Planned Dosing Regimen (Every 8, 12 or 16 Weeks)

    Time frame: Week 100

    Reported categorically for the subjects who completed the study treatment period: every 8 weeks (q8w), Every 12 weeks (q12w), Every 16 weeks (q16w)

  8. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Each Visit up to Week 100 for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  9. Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 4 to Week 52/100 for the Study Eye

    Time frame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defined as the mean change from baseline to the average value over the periods: Week 4 through Week 52, Week 4 through Week 100. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  10. Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 20 to Week 52/100 and Week 28 to Week 52/100 for the Study Eye

    Time frame: Baseline, period Week 20 through Week 52, period Week 20 through Week 100, period Week 28 through Week 52, period Week 28 through Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defined as the mean change from baseline to the average value over the periods: Week 20 through Week 52, Week 20 through Week 100, Week 28 through Week 52, Week 28 through Week 100. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  11. Average Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Over the Period Week 88 to 100 for the Study Eye

    Time frame: Baseline, period Week 88 through Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. For each participants, this endpoint was defined as the mean change from baseline to the average value over the period Week 88 through Week 100. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  12. Percentage of Participants Who Gained >= 5 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  13. Percentage of Participants Who Gained >= 10 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  14. Percentage of Participants Who Gained >= 15 Letters in BCVA From Baseline or Reached BCVA >= 84 Letters at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  15. Percentage of Participants Who Lost >= 5 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  16. Percentage of Participants Who Lost >= 10 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  17. Percentage of Participants Who Lost >= 15 ETDRS Letters in Best Corrected Visual Acuity (BCVA) From Baseline at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  18. Percentage of Participants With an Absolute Best Corrected Visual Acuity (BCVA) >= 73 ETDRS Letters at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The overall BCVA score (number of letters read correctly by the patient) was calculated using the BCVA worksheet 0-100 letter score, with higher score indicating improvement in acuity. A positive change from baseline is a favorable outcome. BCVA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  19. Mean Change From Baseline in Central Subfield Thickness (CSFT) at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. a negative change from baseline indicates a reduction in thickness, whereas a positive change from baseline indicates an increase. An increase in thickness may indicate a progression of the underlying disease. CSFT assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  20. Average Mean Change From Baseline in Central Subfield Thickness (CSFT) Over the Period Week 40 Through Week 52 / Week 88 Through Week 100 for the Study Eye

    Time frame: Baseline, period Week 40 through Week 52, period Week 88 through Week 100

    The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. a negative change from baseline indicates a reduction in thickness, whereas a positive change from baseline indicates an increase. An increase in thickness may indicate a progression of the underlying disease. CSFT assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment. For each participants, this endpoint was derived as the average of the changes from Baseline to Weeks 40, 44, 48, 52. Then the same was derived over the period Week 88 through Week 100, considering the average of the changes from Baseline to Weeks 88, 92, 96, 100. This endpoint was only assessed in the year-2 analysis (Week 100).

  21. Average Mean Change From Baseline in CSFT Over the Period Week 4 to Week 52 / 100 for the Study Eye

    Time frame: Baseline, period Week 4 through Week 52, period Week 4 through Week 100

    The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. a negative change from baseline indicates a reduction in thickness, whereas a positive change from baseline indicates an increase. An increase in thickness may indicate a progression of the underlying disease. CSFT assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  22. Percentage of Participants With Normal CSFT Thickness (<280 Micrometers) at Each Post-baseline Visit for the Study Eye

    Time frame: Baseline, Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. CSFT assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  23. Percentage of Patients With Presence of Subretinal Fluid (SRF) in the Study Eye at Each Post-baseline Visit

    Time frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Presence of Subretinal Fluid (SRF) in the study eye was assessed by spectral domain optical coherence tomography (SD-OCT), angiography, and/or color fundus photography. Subretinal fluid status assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  24. Percentage of Patients With Presence of Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit

    Time frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Presence of Intraretinal Fluid (IRF) in the study eye was assessed by spectral domain optical coherence tomography (SD-OCT), angiography, and/or color fundus photography. Intraretinal fluid status assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  25. Percentage of Patients With Presence of Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) in the Study Eye at Each Post-baseline Visit

    Time frame: Week 4, Week 6, Week 8, Week 12, Week 16, Week 18, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48, Week 52, Week 56, Week 60, Week 64, Week 68, Week 72, Week 76, Week 80, Week 84, Week 88, Week 92, Week 96, Week 100

    Presence of Subretinal Fluid (SRF) and/or Intraretinal Fluid (IRF) in the study eye was assessed by spectral domain optical coherence tomography (SD-OCT), angiography, and/or color fundus photography. Fluid status (SRF and/or IRF) assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  26. Percentage of Participants With Presence of Leakage on Fluorescein Angiography (FA) at Weeks 52 and 100

    Time frame: Week 52, Week 100

    Presence of leakage on Fluorescein Angiography as assessed by fluorescein angiography. Leakage on FA assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  27. Percentage of Participants With With >=2-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. DRSS assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  28. Percentage of Participants With With >=3-step Improvement From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The Diabetic Retinopathy Disease Severity Scale measures the 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. DRSS assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  29. Percentage of Participants With With >=2-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The Diabetic Retinopathy Disease Severity Scale was based on 7-field stereo color fundus photography and measured 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. DRSS assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  30. Percentage of Participants With With >=3-step Worsening From Baseline in ETDRS Diabetic Retinopathy Severity Scale (ETDRS-DRSS) Score

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The Diabetic Retinopathy Disease Severity Scale was based on 7-field stereo color fundus photography and measured 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. DRSS assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  31. Percentage of Participants With Progression to Proliferative Diabetic Retinopathy (PDR) as Assessed by ETDRS-DRSS Score of at Least 61 by Week 100

    Time frame: Week 100

    The Diabetic Retinopathy Disease Severity Scale was based on 7-field stereo color fundus photography and measured 5 levels of diabetic retinopathy - none, mild, moderate, severe, and proliferative. DRSS assessments after start of alternative diabetic macular edema (DME) treatment in the study eye were censored and replaced by the last value prior to start of this alternative treatment.

  32. Number of Participants With Ocular and Non-ocular Adverse Events (AEs)

    Time frame: From randomization till 30 days safety follow-up, assessed up to 35 months.

    The number of participants with ocular and non-ocular adverse events was was assessed by CTCAE and reported categorically: Mild, Moderate, Severe.

  33. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Composite Score

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  34. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - General Vision

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  35. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Ocular Pain

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  36. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Near Activities

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  37. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Distance Activities

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  38. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Social Functioning

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  39. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Mental Health

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  40. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Role Difficulties

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  41. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Dependency

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  42. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Driving

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  43. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Color Vision

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  44. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): Subscale Score - Peripheral Vision

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  45. Change From Baseline in the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25): General Health Rating

    Time frame: Baseline, Week 28, Week 52, Week 76, Week 100

    The survey consisted of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranged from 0 (worst) to 100 which indicated the best possible response. The composite score and score of each construct also ranged from 0 to 100 as they were calculated as total scores divided by the number of questions. The higher the values of total scores represented better outcome.

  46. Systemic Brolucizumab Concentration

    Time frame: Up to Week 24

    Serum samples were taken approximately 24 hours after the first dose and 24 hours after the treatment at Week 24 to confirm the systemic brolucizumab exposure in patients with visual impairment due to diabetic macular edema.

  47. Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm

    Time frame: Up to Week 100

    Integrated ADA Status was categorized: ADA negative or ADA positive with no boost, Induced or Boosted, Missing ADA at pre-dose or no post-dose ADA data.

    • ADA negative: (a) ADA negative at all time points (pre-dose and post-dose), (b) ADA negative at pre-dose and no titer values above 40 at all other time points, (c) ADA titer of 40 at pre-dose but negative at all other time points.
    • ADA positive with no boost: ADA positive at pre-dose, post-dose titer values do not increase from pre-dose by more than 3-fold (1 dilution) at any time point.
    • Induced: ADA negative at pre-dose, post-dose titer value of 120 or more at any time point.
    • Boosted: ADA positive at pre-dose, post-dose titer values increase from pre-dose by more than 3-fold (1 dilution) at any time point.

  48. Distribution of Integrated Anti-Drug Antibody (ADA) Status in the Brolucizumab Arm - Adjusted for Pre-existing ADA Status

    Time frame: Up to Week 100

    Integrated ADA Status - adjusted for pre-existing ADA status was categorized: ADA negative, ADA positive with no boost, Induced, Boosted.

    • ADA negative: (a) ADA negative at all time points (pre-dose and post-dose), (b) ADA negative at pre-dose and no titer values above 40 at all other time points, (c) ADA titer of 40 at pre-dose but negative at all other time points.
    • ADA positive with no boost: ADA positive at pre-dose, post-dose titer values do not increase from pre-dose by more than 3-fold (1 dilution) at any time point.
    • Induced: ADA negative at pre-dose, post-dose titer value of 120 or more at any time point.
    • Boosted: ADA positive at pre-dose, post-dose titer values increase from pre-dose by more than 3-fold (1 dilution) at any time point.

  49. Pre-existing ADA Status and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye

    Time frame: Up to Week 100

    Pre-existing ADA status and incidence of Adverse Event of Special Interest (AESI) in the study eye was categorized: Negative, Positive.

  50. Integrated ADA Status up to Week 100 and Incidence of Adverse Event of Special Interest (AESI) in the Study Eye.

    Time frame: Up to Week 100

    Integrated ADA status up to Week 100 and incidence of Adverse Event of Special Interest (AESI) in the study eye was categorized: ADA-negative or no boost, Induced or boosted.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Two-Year, Two-Arm, Randomized, Double Masked, Multicenter, Phase III Study Assessing the Efficacy and Safety of Brolucizumab Versus Aflibercept in Adult Patients With Visual Impairment Due to Diabetic Macular Edema

Acronym: KITE

Important dates

Study start
2018
Primary completion
2020
Study completion
2021
First posted
Mar 29, 2018
Registry last updated
Jan 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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