Abstract
Purpose :
RP is an incurable blinding disease caused by death of first rod, then cone, photoreceptors in the retina. Preclinical studies have demonstrated that transplantation of retinal progenitor cells into the eye can significantly slow photoreceptor loss. We assessed the safety and activity of human retinal progenitor cells (hRPC) in a first-in-human clinical study.
Methods :
A phase 1/2a multicenter open-label study (NCT02320812) evaluated 28 patients (ages 18 -73 years) with RP in two vision cohorts: best-corrected visual acuity (BCVA) in the treated eye was between 20/200 and “hand motions” in the first cohort and 20/63-20/200 in the second. Patients received a single intravitreal injection of 0.5, 1.0, 2.0 or 3.0 million hRPC (jCell; jCyte, Newport Beach, CA) . Safety and efficacy were evaluated at scheduled intervals through 12 months post-treatment. Safety was demonstrated at each dose level in cohort 1 subjects before proceeding to a higher dose level in the same cohort and before cohort 2 subjects could be enrolled at the same dose level.
Results :
Treatment-related adverse events were reported in 21 subjects (75.0%) and were mostly mild to moderate and transient. Although the study was not powered or designed to assess efficacy, BCVA and other parameters were monitored over 12 months. Vision of hand motions or counting fingers were scored as zero letters correct for purposes of analysis. Mean change in BCVA from pre-treatment to month 12 (treated eye minus untreated eye) was 3.64 letters for all study subjects, 1.38 letters for the 0.5M dose group, 1.00 letter for the 1.0M dose group, 4.83 letters for the 2.0M dose group and 9.00 letters for 3.0M hRPC. When subjects without measurable BCVA at baseline (n = 8) were excluded the difference in mean change in BCVA (treated eye - untreated eye) at 12 months was 1.83 letters for the 0.5M dose group, 0.17 letters for the 1.0M dose group, 7.50 letters for the 2.0M dose group and 11.25 letters for 3.0M hRPC.
Conclusions :
Intravitreal injection of hRPC was safe and well-tolerated at doses up to 3 million cells. The change in BCVA between treated and untreated eyes was positive at all dose levels, with suggestion of a dose response at the higher dose levels. A phase 2b masked, controlled study designed to confirm efficacy using BCVA and other potentially more sensitive endpoints is currently ongoing.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.