Trial reportLancet (London, England)2017
Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.
Trial report in Lancet (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 2 registered trials, which are not on this map. Cited by 1,103 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis (LCA) Using Adeno-Associated Viral Vector to Deliver the Gene for Human RPE65 to the Retinal Pigment Epithelium (RPE) [AAV2-hRPE65v2-301]
Biomarkers for Prognosis in Different Forms of Retinitis Pigmentosa
Who cites it
1,103 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,826 citations in OpenAlex.
- Mapping the intellectual landscape and emerging trends of retinitis pigmentosa research.Frontiers in medicine · 2026Pooled it
- Retinal Viral Gene Therapy: Impact of Route of Administration on Serious Adverse Events-A Systematic Review.Clinical & experimental ophthalmology · 2025Pooled it
- Safety and vision outcomes of subretinal gene supplementation therapy inThe British journal of ophthalmology · 2026Trial
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Gene regulatory behaviors of mutant CRX proteins demonstrated with late-stage human retinal organoids.Human molecular genetics · 2026Article
- Unilateral subretinal administration of HORA-PDE6β in patients with retinitis pigmentosa harbouring mutations in theBMJ open ophthalmology · 2026Article
- Assessing awareness toward genetic testing among patients with inherited retinal dystrophy in Japan.Japanese journal of ophthalmology · 2026Article
- Current translational perspectives for diagnosis and individualized therapy in rare genetic diseases.Communications medicine · 2026Review
- [Pioneering trials in ophthalmology-From clinical trials to guideline treatment].Die Ophthalmologie · 2026Article
- [From phase I-IV-Correctly understand and assess study designs in ophthalmology].Die Ophthalmologie · 2026Article
- Deep Learning for Diagnosis of Choroideremia andOphthalmology science · 2026Article
- Next-Generation Therapies for Genetic Diseases: The Synergy of CRISPR and Gene Therapy.Biochemical genetics · 2026Review
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Review
- Impact of Extraction Recovery and Matrix Effect on qPCR-based Biodistribution Analysis in Gene Therapy: Strategies for Mitigation.The AAPS journal · 2026Article
- Visual field and driving performance of individuals with inherited retinal disorders: a scoping review.BMJ open ophthalmology · 2026Article
- Observational
- First pilot study of intrastromal rAAV-PAX6 gene therapy suggests improved corneal thickness and transcription correction in aniridic mouse.Molecular therapy. Advances · 2026Article
1,043 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
36 authors at 10 institutions in 3 countries.
Funding
Abstract
backgroundPhase 1 studies have shown potential benefit of gene replacement in RPE65-mediated inherited retinal dystrophy. This phase 3 study assessed the efficacy and safety of voretigene neparvovec in participants whose inherited retinal dystrophy would otherwise progress to complete blindness.
methodsIn this open-label, randomised, controlled phase 3 trial done at two sites in the USA, individuals aged 3 years or older with, in each eye, best corrected visual acuity of 20/60 or worse, or visual field less than 20 degrees in any meridian, or both, with confirmed genetic diagnosis of biallelic RPE65 mutations, sufficient viable retina, and ability to perform standardised multi-luminance mobility testing (MLMT) within the luminance range evaluated, were eligible. Participants were randomly assigned (2:1) to intervention or control using a permuted block design, stratified by age (<10 years and ≥10 years) and baseline mobility testing passing level (pass at ≥125 lux vs <125 lux). Graders assessing primary outcome were masked to treatment group. Intervention was bilateral, subretinal injection of 1·5 × 10
findingsBetween Nov 15, 2012, and Nov 21, 2013, 31 individuals were enrolled and randomly assigned to intervention (n=21) or control (n=10). One participant from each group withdrew after consent, before intervention, leaving an mITT population of 20 intervention and nine control participants. At 1 year, mean bilateral MLMT change score was 1·8 (SD 1·1) light levels in the intervention group versus 0·2 (1·0) in the control group (difference of 1·6, 95% CI 0·72-2·41, p=0·0013). 13 (65%) of 20 intervention participants, but no control participants, passed MLMT at the lowest luminance level tested (1 lux), demonstrating maximum possible improvement. No product-related serious adverse events or deleterious immune responses occurred. Two intervention participants, one with a pre-existing complex seizure disorder and another who experienced oral surgery complications, had serious adverse events unrelated to study participation. Most ocular events were mild in severity.
interpretationVoretigene neparvovec gene replacement improved functional vision in RPE65-mediated inherited retinal dystrophy previously medically untreatable.
fundingSpark Therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.