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Completed

NCT Number: NCT04030962

A Study of the Drugs AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

This was a 2-stage study in which Stage 1 evaluated the safety of AGN-242428 and AGN-231868, how well they are tolerated, and how they move through the body when administered. After the sponsor's determination of adequate safety and tolerability of the interventions in Stage 1, Stage 2 began. Stage 2 also evaluated the safety and tolerability of AGN-242428 and AGN-231868, how effective they are in treating dry eye disease (DED), and assessed the plasma and tear exposure of both ophthalmic solutions.

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Key information

Conditions

Dry Eye Disease Dry Eye Syndrome Dry Eye Syndromes Eye Diseases Lacrimal Apparatus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Cornea and Cataract Consultants of Arizona /ID# 232769, Phoenix, Arizona, United States

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About this study

Participants with DED in Cohort 1A were randomized 3:3:1:1 to receive AGN-242428 (Low Dose), AGN-231868 (Low Dose), or their respective vehicles (4 treatment groups total) to the left eye on Day 1 (Visit 2). If there were no significant study drug-related safety findings, starting on Day 2, participants administered the same randomized study drug twice daily to both eyes through Day 14, followed by a single dose administration to both eyes on Day 15 (Visit 5).

Upon completion of Cohort 1A, an independent data monitoring committee reviewed the data before proceeding to the next cohort. Cohort 1B participants were randomized 3:3:1:1 to receive AGN-242428 (High Dose), AGN-231868 (High Dose), or their respective vehicles (4 treatment groups total) and followed the same dosing regimen used in Cohort 1A.

All subjects enrolled in Stage 2 had DED. In addition, subjects were selected based on their response to a controlled adverse environment (CAE). Only subjects with DED who responded to the CAE exposure with an increase in the signs and symptoms of DED were enrolled in Stage 2.

During Stage 2, participants were randomized in a 1:1:1:1:1 ratio (within each site), to receive AGN-242428 (High Dose), AGN-242428 vehicle, AGN-231868 (High Dose), AGN-231868 vehicle, or Lifitegrast Ophthalmic Solution (Xiidra). Participants administered the assigned study drug in each eye twice daily for 41 days, followed by a single administration during the morning on Day 42.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

Stage 1 & Stage 2:

  • Male participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study.
  • Female participants willing to minimize the risk of inducing pregnancy for the duration of the clinical study.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.

Stage 1:

  • Both of the following signs of DED in at least 1 eye at Screening and Baseline visits (the same eye does not need to qualify at both visits):
  • Total corneal fluorescein staining score ≥ 2 and ≤ 9 based on the NEI grading scale, with no score > 2 in any 1 region;
  • Schirmer test with topical anesthesia score ≥ 1 and ≤ 10 mm/5 min.

Stage 2:

  • ALL of the following in at least 1 eye at both the Screening and Baseline visits and the same eye must qualify at both Screening and Baseline visits:
  • Corneal fluorescein staining score ≥ 2 in at least 1 eye region and a total corneal fluorescein staining score of ≥ 4 and ≤ 12 based on NEI grading scale;
  • Schirmer test with topical anesthesia score ≥ 2 and ≤ 10 mm/5 min;
  • Mean TBUT of ≥ 2 and ≤ 10 seconds.

Stage 1:

  • Symptoms of DED at both the Screening and Baseline visits as defined by an OSDI total score of ≥ 13 with ≤ 3 responses of "not applicable (NA)."

Stage 2:

  • Symptoms of DED at both the Screening and Baseline visits as defined by both:
  • OSDI score of ≥ 23 with ≤ 3 responses of "not applicable (NA)" in at least 1 eye;
  • Eye Dryness Score (assessed using the Visual Analog Scale [VAS] Symptom Items score ≥ 30).

Exclusion criteria

  • Current diagnosis of glaucoma or ocular hypertension; evidence of glaucoma or mean intraocular pressure > 21 mm Hg determined by Goldmann applanation tonometry, in either eye.
  • Diagnosis of recurrent, ongoing, or active ocular infection including, but not limited to herpes simplex or zoster, vaccinia, varicella, tuberculosis of the eye, acanthamoeba, or fungal disease.
  • Participation in a blood or plasma donation program within 60 or 30 days, respectively, prior to study intervention administration.
  • Positive test results for anti-HIV type 1 and 2, hepatitis B surface antigen, or anti-hepatitis C virus at the Screening visit.
  • Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at the Screening or Baseline visits.
  • Positive pregnancy test at Screening or Baseline visits.
  • Currently breastfeeding or plans to breastfeed during the study.
  • History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or participant safety.

Treatment and study plan

AGN-242428

Drug

Ophthalmic solution administered as a topical eye drop

AGN-231868

Drug

Ophthalmic solution administered as a topical eye drop

AGN-242428 Vehicle

Other

Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop

AGN-231868 Vehicle

Other

Matching placebo (vehicle) ophthalmic solution administered as a topical eye drop

Lifitegrast 5% Ophthalmic Solution

Drug

Ophthalmic solution administered as a topical eye drop

Other names: Xiidra

Primary outcomes

  1. Stage 1: Number of Participants With Adverse Events

    Time frame: Day 1 to Day 15

    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

  2. Stage 1: Area Under the Plasma Concentration Versus Time Curves After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the area under the plasma concentration versus time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the plasma concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.

  3. Stage 1: Area Under the Tear Concentration Versus Time Curves After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the area under the tear concentration versus (vs) time curves from time 0 to time of the last measurable concentration (AUC0-tlast; Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the area under the tear concentration versus time curves from time 0 to the end of the dosing interval (AUC0-τ; Visit 5) was calculated. For Visit 3 and Visit 5, tlast was 12 hours post-dose.

  4. Stage 1: Maximum Plasma Drug Concentration (Cmax) After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the plasma Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Cmax (Visit 5) was calculated.

  5. Stage 1: Maximum Tear Drug Concentration (Cmax) After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the tear Cmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Cmax (Visit 5) was calculated.

  6. Stage 1: Time of Maximum Plasma Drug Concentration (Tmax) After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the plasma Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the plasma Tmax (Visit 5) was calculated.

  7. Stage 1: Time of Maximum Tear Drug Concentration (Tmax) After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the tear Tmax (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, the tear Tmax (Visit 5) was calculated.

  8. Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Single Dose Administration

    Time frame: Day 2 (Predose and up to 12 hours postdose).

    Following single dose administration, the plasma T1/2 (Day 2; Visit 3) was calculated.

  9. Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Plasma After Repeat Dose Administration

    Time frame: Day 15 (Predose and up to 12 hours postdose)

    Following repeat dose administration twice daily for 14 days, plasma T1/2 (Day 15; Visit 5) was calculated.

  10. Stage 1: Terminal Elimination Half-life of the Study Drugs (T1/2) in Tear After Single and Repeat Dose Administration

    Time frame: Day 2 and Day 15 (Predose and up to 12 hours postdose)

    Following single dose administration, the tear T1/2 (Visit 3) was calculated. Following repeat dose administration twice daily for 14 days, tear T1/2 (Visit 5) was calculated.

  11. Stage 1: Minimum Tear Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration

    Time frame: Day 15 (Predose and up to 12 hours postdose)

    Following repeat dose administration twice daily for 14 days, the tear Cmin,ss (Visit 5) was calculated.

  12. Stage 1: Minimum Plasma Drug Concentration at Steady State (Cmin,ss) After Repeat Dose Administration

    Time frame: Day 15 (Predose and up to 12 hours postdose)

    Following repeat dose administration twice daily for 14 days, the plasma Cmin,ss (Visit 5) was calculated.

  13. Stage 1: Mean Accumulation Index of Drug Concentration (AI) After Repeat Dose Administration

    Time frame: Day 15 (up to 12 hours) / Day 1 (up to 12 hours)

    Following repeat dose administration, the mean plasma and tear AI(area under curve [AUC]) was calculated. AI(AUC) is reported as the ratio of exposure (AUC) at steady state (Day 15) to the exposure after a single daily dose (Day 1). Values greater than one are indicative of drug accumulation with repeat dosing.

  14. Stage 1: Mean Drop Tolerability Questionnaire Scores

    Time frame: Day 15

    Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention.

  15. Stage 1: Percentage of Participants Who Met Criteria for Potentially Clinically Significant (PCS) Clinical Laboratory Values

    Time frame: Day 1 to Day 15

    The percentage of participants with non-PCS baseline value and met PCS criterion at least once postbaseline for clinical laboratory values.

  16. Stage 1: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)

    Time frame: Day 1 to Day 15

    The percentage of participants who met PCS criteria at least once postbaseline for vital sign values (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature)

  17. Stage 1: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values

    Time frame: Day 1 to Day 15

    The percentage of participants with PCS postbaseline (but not at baseline) ECG values for QRS interval, PR interval, and QTc (Fridericia)

  18. Stage 1: Mean Change From Baseline in Intraocular Pressure (IOP)

    Time frame: Day 1 to Day 15

    At least 2 measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated.

  19. Stage 1: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)

    Time frame: Day 1 to Day 15

    BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol.

  20. Stage 1: Biomicroscopy: Percentage of Participants With Any Severity Increase From Baseline

    Time frame: Day 1 to Day 15

    The number of participants with any ophthalmoscopy findings of any severity increase from baseline at one or more visit.

  21. Stage 1: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination

    Time frame: Day 1 to Day 15

    The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.

  22. Stage 2: Number of Participants With Adverse Events

    Time frame: Day 1 to Day 42

    An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.

  23. Stage 2: Percentage of Participants With Potentially Clinically Significant (PCS) Clinical Laboratory Values

    Time frame: Day 42

    The percentage of participants who have PCS postbaseline clinical laboratory values at Day 42 (Visit 6).

  24. Stage 2: Percentage of Participants Who Met Criteria for PCS Vital Sign Values (Blood Pressure, Pulse Rate, Weight, Respiration Rate, and Temperature)

    Time frame: Day 42

    The percentage of participants who met PCS criteria at least once postbaseline for vital sign values at Day 42 (Visit 6) (sitting systolic and diastolic blood pressure, pulse rate, weight, respiration rate, and temperature). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.

  25. Stage 2: Percentage of Participants Who Met Criteria for PCS Electrocardiogram (ECG) Values

    Time frame: Day 42

    The percentage of participants who have PCS ECG at Visit 6 (but not baseline) pre and post-controlled adverse environment (CAE). The numerator for the incidence is the number of participants with non-PCS baseline and at least one post-baseline value meeting the specific criterion at the visit. The denominator is the number of participants with non-PCS baseline and at least one post-baseline assessment at the visit. If a participant did not have a baseline value, but met the criterion post-baseline, then the participant is counted in the numerator.

  26. Stage 2: Mean Change From Baseline in Intraocular Pressure (IOP)

    Time frame: Day 1, Day 42

    At least 2 IOP measurements were taken by qualified study site personnel using a Goldmann applanation tonometer affixed to a slit lamp with the participant seated. Average intraocular pressure = mean of the 2 (or 3) measures in the study eye and non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.

  27. Stage 2: Mean Change From Baseline in Best-corrected Visual Acuity (BCVA)

    Time frame: Day 1, Day 42

    BCVA was quantified using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol in the study eye and the non-study eye. Total fluorescein scores and Schirmer values were used to determine the study eye, and if both eyes qualified, the right eye was designated by default.

  28. Stage 2: Slit-lamp Biomicroscopy: Percentage of Participants With Any Clinically Significant Finding Postbaseline

    Time frame: Day 1 to Day 42

    Percentage of participants with a clinically significant finding postbaseline, post-CAE. A clinically significant finding is defined as more than one severity grade increase (worsening) from baseline or positive status change from absence at baseline to presence at postbaseline (not associated with a severity grade) in one or both eyes.

  29. Stage 2: Percentage of Participants With Any Clinically Significant Postbaseline Findings During Dilated Fundus Examination

    Time frame: Day 1 to Day 42

    The fundus (posterior pole; periphery, when dilated) was evaluated for pathology. Ophthalmoscopy with clinically significant findings (per investigator assessment) postbaseline are reported.

  30. Stage 2: Drop Tolerability Questionnaire Score (Post-controlled Adverse Environment)

    Time frame: Day 42 (Post-CAE)

    Acute overall tolerability attributes of study interventions on an 8-question visual analog scale (VAS) Drop Tolerability Questionnaire. Participants completed questionnaires after exposure to a controlled adverse environment (CAE) for approximately 90 minutes. Visual scale ranges from 0 = not at all comfortable to 100 = very comfortable. Higher mean scores indicate higher levels of comfort with the assigned intervention.

Secondary outcomes

  1. Stage 2: Trough Plasma Concentration (Ctrough) and Plasma Concentration at 0.5 Hours Postdose (C0.5h)

    Time frame: Day 42

    Trough plasma concentration (Ctrough) and plasma concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks

  2. Stage 2: Trough Tear Concentration (Ctrough) and Tear Concentration at 0.5 Hours Postdose (C0.5h)

    Time frame: Day 42

    Trough tear concentration (Ctrough) and tear concentration at 0.5 hours postdose (C0.5h), following twice daily dosing for up to 6 weeks

Sponsors and collaborators

Lead sponsor

AbbVie

Industry

Registry information

Official study title

A Multicenter, Vehicle-controlled, Double-Masked, Randomized Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of AGN-242428 and AGN-231868 in Participants With Dry Eye Disease

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Jul 24, 2019
Registry last updated
May 20, 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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