Clinical Proof-of-Concept Study of Oral Synthetic cis-Retinoid (QLT091001) In Adult Subjects With Impaired Dark Adaptation and/or Impaired Low Luminance Vision

Abstract

Purpose: To explore and assess the safety and visual outcomes of treatment with oral 9-cis-retinyl acetate (QLT091001) in subjects with early age-related macular degeneration and impaired dark adaptation and/or impaired low luminance low contrast best corrected visual acuity (LLLC BCVA).

Methods: In a multi-center randomized, placebo-controlled, Phase 2a study, 43 subjects, 60 to 90 years of age, who met eligibility criteria were randomized to receive placebo (11 subjects), 10 mg/m² (16 subjects), or 40 mg/m² (16 subjects) oral doses of QLT091001 on Days 0, 7, 14 and 15. Dark adaptation rates, glare recovery times, and LLLC BCVA were assessed at baseline, prior to dosing on Days 7, 14, and 15, and at follow-up visits on Days 17, 28, and 42. Safety assessments included high luminance high contrast BCVA, ophthalmic examination, vital signs, electrocardiogram, laboratory testing and adverse events.

Results: In subjects with impaired dark adaptation at baseline (rod-cone break [RCB] time ≥9.0 min; n=14), an improvement in RCB time (assessed as median change from baseline) was observed in subjects treated with QLT091001 (10 mg/m² and 40 mg/m² combined; n=10) at all assessments. In comparison, RCB time for the placebo group showed improvement at only one visit. For glare recovery, subjects treated with QLT091001 (10 mg/m² and 40 mg/m² combined; n=20) showed improved glare recovery times (median change from baseline) at 5 of 6 assessments while those treated with placebo (n=7) showed mixed results across assessments. A clear treatment effect on LLLC BCVA was not observed using the protocol and procedures of this study. The most common treatment-related adverse event was headache and was observed in the 40 mg/m² group only (5 of 16 subjects). Two subjects withdrew from the study - one due to a treatment related headache and one due to SAEs unrelated to treatment.

Conclusions: Oral doses of QLT091001 dosed once per week for 3 consecutive weeks with one additional dose the day after the third dose showed trends in improvement in dark adaptation rate and in glare recovery time relative to placebo. QLT091001 treatment had an acceptable safety profile and was well-tolerated. Further development of QLT091001 in this indication is warranted.