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

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

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.

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.

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.