Trial reportNature medicine2022
Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial.
Trial report in Nature medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03140969 (An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis), which is not on this map. Cited by 92 papers, 1 of them a synthesis 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.
An Open-label, Multiple Dose, Dose Escalation Study to Evaluate the Safety and Tolerability of QR-110 in Subjects With Leber's Congenital Amaurosis (LCA) Due to c.2991+1655A>G Mutation (p.Cys998X) in the CEP290 Gene
Who cites it
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- ISCEV and IPS guideline for the full-field stimulus test (FST).Documenta ophthalmologica. Advances in ophthalmology · 2024Guideline
- Gene Editing forThe New England journal of medicine · 2024Trial
- Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.Molecular therapy. Nucleic acids · 2026Article
- Research Progress on the Pathogenesis and Diagnostic and Therapeutic Potential of Ciliopathies Regulated by IFT172.Clinical genetics · 2026Review
- Assessment of full-field stimulus test results in Stargardt disease: correlations with full-field electroretinography, multifocal electroretinography, and optical coherence tomography.Documenta ophthalmologica. Advances in ophthalmology · 2026Article
- Modalities of vision restoration in optic neuropathies and retinal disease.Progress in retinal and eye research · 2026Review
- Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy.Molecular therapy. Nucleic acids · 2026Article
- Precision Medicine in Inherited Retinal Disease: Advances, Challenges, and Future Directions.Journal of personalized medicine · 2026Review
- Genetic Testing in Inherited Retinal Disease: Current Strategies and Future Directions.Journal of personalized medicine · 2026Review
- Enhanced splicing modulation by NMA-modified antisense oligonucleotides.Nucleic acids research · 2026Article
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Antisense Oligonucleotides: Technological Advances, Clinical Progress, and Expanding Therapeutic Frontiers.Pharmaceutics · 2026Review
- A Homozygous Deep Intronic SNX14 Variant Activates Pseudo-Exon Inclusion in a Patient with SCAR20.Genes · 2026Article
- A Comparison of Randomizing Either One Eye or Both Eyes in Clinical Trials for Stargardt Disease Type 1.Ophthalmology science · 2026Article
- A novelInternational journal of ophthalmology · 2026Article
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Article
- Therapeutic antisense oligonucleotide mitigates retinal dysfunction in a pig model of CLN3 Batten disease.Nucleic acids research · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
32 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CEP290-associated Leber congenital amaurosis type 10 (LCA10) is a retinal disease resulting in childhood blindness. Sepofarsen is an RNA antisense oligonucleotide targeting the c.2991+1655A>G variant in the CEP290 gene to treat LCA10. In this open-label, phase 1b/2 ( NCT03140969 ), 12-month, multicenter, multiple-dose, dose-escalation trial, six adult patients and five pediatric patients received ≤4 doses of intravitreal sepofarsen into the worse-seeing eye. The primary objective was to evaluate sepofarsen safety and tolerability via the frequency and severity of ocular adverse events (AEs); secondary objectives were to evaluate pharmacokinetics and efficacy via changes in functional outcomes. Six patients received sepofarsen 160 µg/80 µg, and five patients received sepofarsen 320 µg/160 µg. Ten of 11 (90.9%) patients developed ocular AEs in the treated eye (5/6 with 160 µg/80 µg; 5/5 with 320 µg/160 µg) versus one of 11 (9.1%) in the untreated eye; most were mild in severity and dose dependent. Eight patients developed cataracts, of which six (75.0%) were categorized as serious (2/3 with 160 µg/80 µg; 4/5 with 320 µg/160 µg), as lens replacement was required. As the 160-µg/80-µg group showed a better benefit-risk profile, higher doses were discontinued or not initiated. Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development.
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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 Socratic graph.