Abstract
Purpose :
Rod-cone dystrophy (RCD) is a rare inherited retinal disorder leading to significant vision loss, and for which no treatment is currently available to most patients. SPVN06 is a gene-independent investigational gene therapy expressing the neurotrophic rod-derived cone viability factor (RdCVF) and the thioredoxin RdCVF-Long (RdCVFL), that aims at slowing down the progression of central vision loss in patients with RCD, regardless of the underlying pathogenic variant(s).
Methods :
PRODYGY (NCT05748873) is a first-in-human Phase I//II trial enrolling subjects with advanced RCD due to a mutation in the RHO, PDE6A, or PDE6B gene. The study will assess the safety and tolerability of a unilateral subretinal injection of SPVN06, one year after treatment administration. Its two-step design includes an open-label dose-escalation phase (Step 1) followed by a controlled, double-masked, randomized, extension phase (Step 2). Step 1 will test 3 increasing doses of SPVN06 in subjects with severe advanced RCD, and two doses will be selected for assessment in Step 2. Step 2 will include 3 cohorts of subjects with intermediate advanced RCD. A total of 33 subjects is planned to be enrolled, of whom 27 will receive a single injection of SPVN06 in their worse-seeing eye.
Results :
In the first cohort of 3 subjects treated at the lowest dose, 3 adverse events (AEs) of subconjunctival hemorrhage, and 1 AE of special interest (AESI) of transient intraocular pressure elevation were reported in the weeks following subretinal injection. All ocular AEs were mild and resolved without further intervention. Transient grade-1 vitreous haze and cells were also observed in 2 subjects, and resolved without treatment. A transient increase in anti-AAV8 antibodies, peaking at Week 2, was observed in 1 subject who had pre-existing antibodies before injection of SPVN06. No cellular immune response against the viral capsid or the transgenic peptides was observed. An independent Data Safety Monitoring Board provided a positive recommendation to continue the trial as planned, and treatment administration is ongoing in the second cohort. To date, no dose-limiting toxicities have been observed.
Conclusions :
First administration of SPVN06 to patients at a low dose showed a favorable safety profile of the procedure and no significant immune response.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.