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Completed

NCT Number: NCT04630158

Study of Efficacy and Safety of SAF312 Eye Drops in Subjects With Post-operative Corneal Induced Chronic Pain (CICP)

The study was designed to demonstrate the safety and efficacy of two dose concentrations of SAF312 eye drops (5 mg/mL and 15 mg/mL) in subjects with CICP persisting at least for 4 months after refractive or cataract surgery and chronicity confirmed during the observational period. The study also determined the optimal dose to carry forward for further development.

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Key information

Conditions

Chronic Ocular Pain Eye Diseases Eye Manifestations Eye Pain Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Sapporo, Hokkaido, Japan

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About this study

This was a Phase II randomized, double-masked, multi-center, parallel group, placebo-controlled study to evaluate the safety and efficacy of SAF312, 5 mg/mL and 15 mg/mL eye drops versus Placebo used twice-daily in both eyes for 12 weeks. The study consisted of a 12-week observation period starting from Screening Visit (Visit 1) until the Baseline/Randomization Visit (Visit 2). Subjects who met eligibility criteria at Visit 2 were randomized to one of the three treatment arms (SAF312 5 mg/mL, SAF312 15 mg/mL, Placebo) in a 1:1:1 ratio. Subjects who qualified for randomization had visits every 2 weeks for the first 4 weeks, and then monthly visits for the remainder of the 12-week treatment period.

Who can participate

Healthy volunteers accepted: No

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

Key Inclusion Criteria:

  • Subjects who have undergone refractive surgery (i.e., PRK, LASIK, LASEK, RK, or SMILE) in both eyes or cataract surgery in both eyes, with or without refractive enhancement in one or both eyes, ≥4 months prior to Screening Visit and experiencing persistent ocular surface pain since the surgery, and have been seen by an ophthalmologist or optometrist at least once with complaint of continued ocular pain since surgery.
  • Subjects who demonstrate a ≥ 60% reduction in ocular pain within 5 minutes after instillation of a single topical ocular anesthetic drop at Screening Visit.

At Baseline

  • Subjects with an average pain severity VAS score of ≥ 30 mm based on Daily eDiary for the last 7 days prior to Baseline Visit.
  • Subjects who have reported pain severity >10 mm based on Daily eDiary for > 50% of the days of the observational period (Screening)

Key Exclusion Criteria:

  • Use of nerve growth factor eye drops within 14 days of the Screening Visit
  • Seasonal allergic conjunctivitis, or other acute or seasonal ocular diagnosis that are active at the time of Screening or would be active during the course of the study.
  • Any history of ocular herpes simplex virus or herpes zoster virus infection, or other severe ocular conditions such as graft versus host disease, Stevens-Johnson syndrome or sarcoidosis.
  • Presence of any ocular infection (bacterial, viral, or fungal) within 30 days prior to Screening.
  • Chronic topical ocular medications (ie. cyclosporine, lifitegrast) initiated <6 months prior to Screening Visit, or any anticipated change during the study.
  • Use of ocular or nasal corticosteroids within 30 days of Screening Visit.
  • Use of neuromodulatory medications (eg, gabapentin, pregabalin) or opioid use for non-ocular pain within 30 days of Screening Visit.
  • Chronic medications (both over the counter and prescription) that have not been stable for at least 30 days prior to Screening Visit, or any anticipated change in the chronic medication regimen.
  • Subjects requiring hospitalization within 6 months prior to screening for severe psychiatric disorders (e.g. psychosis, schizophrenia, mania, depression) or major psychiatric illness.

Treatment and study plan

SAF312 Placebo

Other

Topical ocular, suspension eye drops

Other names: Artificial tears

SAF312

Drug

Topical ocular, suspension eye drops

Primary outcomes

  1. Change From Baseline at Week 12 in Ocular Pain Severity Visual Analog Scale (VAS)

    Time frame: Baseline, Week 12

    The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome.

Secondary outcomes

  1. Ocular Pain Severity Visual Analog Scale (VAS): Summary Statistics of Change From Baseline at Day 7 and Day 14

    Time frame: Baseline, Days 7 and 14

    The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome.

  2. Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12

    Time frame: Baseline, Weeks 1 to 12

    The pain frequency Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Frequent' pain on the right) to score the frequency of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain frequency. A negative change from baseline is a positive outcome.

  3. Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12

    Time frame: Baseline, Weeks 2, 4, 8, 12

    Each question in the Ocular Pain Assessment Survey (OPAS) quality of life subscale was scored by the subject on a line marked from 0 (not at all) to 10 (completely) that described how much pain interfered with or affected a particular activity (max score= 10/question). A higher score suggests a higher impact by pain on a particular activity. A negative change from baseline is a positive outcome. There are 7 questions in total regarding Quality of Life. The average score of the 7 Quality of Life questions is reported (mean (SD)).

  4. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

  5. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

  6. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome. A negative change from baseline is a positive outcome.

  7. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

  8. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

  9. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

  10. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

  11. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

  12. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome.

  13. Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye)

    Time frame: Baseline, Weeks 2, 4, 8, 12

    The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome.

  14. Number of Participants With Treatment Emergent Adverse Events

    Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

  15. Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT)

    Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

    MedDRA Version 26.0 was used for the reporting of adverse events.

  16. Summary of Non-ocular Treatment Emergent Adverse Events

    Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

    An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A 12-week Parallel Group, Randomized, Placebo-controlled, Double-blinded, Multi-center Study to Evaluate Efficacy and Safety of 2 Concentrations of SAF312 Eye Drops (5 mg/ml and 15 mg/ml) Used Twice-daily in the Treatment of Post-operative Corneal Induced Chronic Pain (CICP) Following Photorefractive Keratectomy (PRK) or Laser-assisted in Situ Keratomileusis (LASIK) Surgeries

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Nov 16, 2020
Registry last updated
Oct 9, 2024

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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