Sepofarsen injections for LCA10 due to the CEP290 p.Cys998X mutation
A Double-Masked, Randomized, Placebo-Controlled, Paired-Eye Study to Evaluate the Efficacy, Safety and Tolerability of Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Due to the c.2991+1655A>G (p.Cys998X) Mutation in the CEP290 Gene
This study will test whether sepofarsen eye injections can improve vision in children and adults with LCA10 caused by the CEP290 c.2991+1655A>G (p.Cys998X) mutation.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 32 (estimated) |
| Ages | 6 Years and up |
| Sex | All |
| Sponsor | Laboratoires Thea Industry-sponsored |
| Locations | 14 sites (San Francisco, California and 13 other locations) |
| Trial ID | NCT06891443 on ClinicalTrials.gov |
What this trial studies
This is a double-masked, randomized, placebo-controlled paired-eye Phase 3 study in which one eye of each participant is randomized to receive sepofarsen and the other eye receives placebo during the first year. Treatment is given by intravitreal injection every six months, with the sepofarsen-treated eye continuing treatment in year two and the originally placebo-treated eye either continuing placebo or switching to sepofarsen. The trial enrolls participants aged 6 years and older with genetically confirmed homozygous or compound heterozygous CEP290 c.2991+1655A>G (p.Cys998X) mutations and detectable macular outer nuclear layer on OCT. Key outcomes include visual acuity and objective/functional vision measures comparing treated and control eyes.
Who should consider this trial
Good fit: Ideal candidates are people aged 6 or older with a confirmed homozygous or compound heterozygous c.2991+1655A>G (p.Cys998X) CEP290 mutation, BCVA within the study's eligible range, symmetrical disease between eyes, and detectable macular ONL.
Not a fit: People with pathogenic mutations in other inherited retinal disease genes, unrelated ocular conditions that prevent valid eye-to-eye comparison, absent macular ONL, or unstable macular edema are unlikely to receive benefit from this treatment.
Why it matters
Potential benefit: If successful, sepofarsen could improve or stabilize vision for people with LCA10 caused by the CEP290 p.Cys998X mutation.
How similar studies have performed: Earlier phase 1/2 studies of sepofarsen (QR-110) reported vision improvements in some LCA10 patients, which provided the signal for this Phase 3 program.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A\>G mutation in CEP290. 2. Adults: \>=18 years / Minors: 6 to \<18 years. 3. BCVA (FrACT) equal to or worse than logMAR +0.4 (approximate Snellen equivalent 20/50) to +2.9 logMAR based on quantifiable, reliable FrACT. LP subjects with documented evidence of prior better vision eligible. 4. Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline. 5. Detectable ONL in the macular area as determined by the CRC at Screening. Exclusion Criteria: 1. Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes. 2. Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible. 3. Presence of unstable concurrent CME, or subject started on (or changed dose of) topical or systemic carbonic anhydrase inhibitor treatment in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment). 4. Presence of any clinically significant lens opacities/cataracts based on the AREDS lens grading scale. 5. Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
Where this trial is running
San Francisco, California and 13 other locations
- UCSF Wayne and Gladys Valley Center for Vision — San Francisco, California, United States (Recruiting)
- University of Miami - Bascom Palmer Eye Institute — Miami, Florida, United States (Recruiting)
- University of Iowa — Iowa City, Iowa, United States (Recruiting)
- University of Minnesota Medical School — Minneapolis, Minnesota, United States (Recruiting)
- University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics — Philadelphia, Pennsylvania, United States (Recruiting)
- Universitair Ziekenhuis Gent (UZ) — Ghent, Belgium (Recruiting)
- University of Alberta — Edmonton, Alberta, Canada (Recruiting)
- The Hospital for Sick Children - SickKids — Toronto, Ontario, Canada (Recruiting)
- Centre de maladies rares CHNO des Quinze Vingt — Paris, France (Recruiting)
- Justus-Liebig Universität - Department of Ophthalmology — Giessen, Germany (Recruiting)
- Klinikum der Ludwig-Maximilian Universität München — München, Germany (Recruiting)
- University of Tuebingen - Inst. for Ophthalmic Research — Tübingen, Germany (Recruiting)
- Radboud Universitair Medisch Centrum — Nijmegen, Netherlands (Recruiting)
- Moorfields Eye Hospital NHS Foundation Trust — London, United Kingdom (Recruiting)
Study contacts
- Study coordinator: Sepul Bio Patient Advocacy Director
- Email: contact@sepulbio.com
- Phone: +31 617060791
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.