Intravitreal Injection of Allogeneic Human Retinal Progenitor Cells (hRPC) for Treatment of Retinitis Pigmentosa: A Prospective Randomized Controlled Phase 2b Trial

Abstract

Purpose : hRPC secrete neurotrophic factors that promote photoreceptor cell survival and function. This paracrine mechanism has shown promise as a therapy for RP agnostic to genetic subtype. A phase 2b trial was conducted to evaluate intravitreal injection of allogeneic hRPC for treatment of RP.

Methods : Patients with RP and best-corrected visual acuity (BCVA) between 20/80 and 20/800 were randomized to two treatment groups (single injection of 3.0x10⁶ or 6.0x10⁶ hRPC) or sham. The primary efficacy endpoint was mean change in BCVA at month 12. Secondary endpoints included a low luminance mobility test (LLMT), contrast sensitivity (CS), kinetic visual fields (VF), and a visual function questionnaire VA LV VFQ-48 (VFQ). Analyses included a per protocol population and a post hoc analysis in a target subgroup meeting the following criteria: 1) study eye with baseline central fixation, 2) study eye without severely constricted field (≥12° diameter), and 3) study eye did not have significantly worse BCVA than fellow eye (≤15 letters).

Results : 84 total patients were randomized; 8 were excluded from the per protocol analysis for protocol violations and 2 were lost to follow up (N=74). Mean changes in BCVA from baseline to month 12 were +2.81, +2.96, and +7.43 letters in sham (N=26), 3.0x10⁶ hRPC (N=25), and 6.0x10⁶ hRPC (N=23) groups, respectively. In the post hoc analysis of the target subpopulation, mean changes in BCVA from baseline to month 12 were +1.85, -0.15, and +16.27 letters in sham (N=13), 3.0x10⁶ hRPC (N=13), and 6.0x10⁶ hRPC (N=11) groups, respectively (p=0.003 for 6.0x10⁶ hRPC vs sham). Improvements in the 6.0x10⁶ group were also observed in all other secondary endpoints. hRPC treatment was well tolerated with generally minor and transient adverse events; there was one treatment related serious adverse event in the 3.0x10⁶ hRPC arm (ocular hypertension that resolved with treatment), but none in the higher dose arm of 6.0x10⁶ hRPC.

Conclusions : Intravitreal injection of hRPC is a novel approach for treatment of RP, independent of the genetic subtype. This phase 2b study demonstrates a strong safety profile and encouraging biological activity, warranting progression to phase 3.

This is a 2021 ARVO Annual Meeting abstract.