Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: sepofarsen, Placebo IVT.
- Who it may be relevant to
- Registry conditions: Leber Congenital Amaurosis 10, Blindness, Leber Congenital Amaurosis, Sensation Disorders. Basic parameters: from 6 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Belgium, Brazil, Canada, France +4
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
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
Overview
The purpose of this double-masked, randomized, placebo-controlled, paired-eye study is 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.
Detailed description
This is a double-masked, randomized, placebo-controlled, paired-eye study in which one eye of each subject will serve as a control.
At the start of the study the two eyes of each subject will be randomized such that one eye receives sepofarsen and the other eye receives placebo for the first year. In the second year, for all subjects, the eye that was randomized to receive sepofarsen will continue to receive sepofarsen. For the eye that was randomized to placebo in the first year, treatment in the second year will be allocated, as follows: 50% of the eyes will continue to receive placebo, and 50% of the eyes will receive sepofarsen.
Sepofarsen and placebo will be administered via intravitreal injection every 6 months.
Interventions
- Drug sepofarsen
RNA antisense oligonucleotide for intravitreal injection - Other Placebo IVT
Placebo with identical appearance to sepofarsen
Primary outcome measures
- Change from baseline in Best-Corrected Visual Acuity (BCVA) [Time frame: 12 Months]
Secondary outcome measures (12)
- Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) [Time frame: Month 12]
- Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) [Time frame: Month 12]
- Change from baseline in retinal sensitivity as measured by dark-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) [Time frame: Month 12]
- Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF [Time frame: Month 12]
- Change from baseline in retinal sensitivity as measured by light-adapted Full-Field Stimulus Test (FST) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) [Time frame: Month 12]
- Response in BCVA (FrACT), defined as an improvement of at least 0.2 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response in BCVA (FrACT), defined as an improvement of at least 0.3 logMAR from baseline at 12 months and compared between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs), evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response in Low Luminance Visual Acuity (LLVA) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response in Full-Field Stimulus Test (FST) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response in Patient Global Impression of Change (PGI-C) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response in Contrast Sensitivity (CS) defined as clinically relevant improvement between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) at 12 months, evaluated by the percentage of eyes that achieve this improvement. [Time frame: Month 12]
- Response defined as a clinically relevant improvement according to a multimodal assessment in TEs compared to the corresponding response in PCEs at 12 months [Time frame: Month 12]
Eligibility criteria
Inclusion criteria
- Confirmed clinical diagnosis of LCA10 and a molecular diagnosis of homozygosity or compound heterozygosity for the c.2991+1655A>G mutation in CEP290.
- Adults: >=18 years / Minors: 6 to <18 years.
- 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.
- Symmetrical disease between the two eyes as defined by a BCVA (FrACT) within 0.2 logMAR at baseline.
- Detectable ONL in the macular area as determined by the CRC at Screening.
Exclusion criteria
- Mutations in genes other than the CEP290 gene associated with other IRD diseases or syndromes.
- Presence of any ocular pathology in either eye that may make comparison of the eyes not feasible.
- 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).
- Presence of any clinically significant lens opacities/cataracts based on the AREDS lens grading scale.
- Any prior receipt of genetic (RNA or DNA therapy) or stem-cell therapy for ocular or non-ocular disease, including sepofarsen.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Quadruple blind
- Primary purpose
- Treatment
Study locations
United States · 5 centers
- UCSF Wayne and Gladys Valley Center for Vision — San Francisco
- University of Miami - Bascom Palmer Eye Institute — Miami
- University of Iowa — Iowa City
- University of Minnesota Medical School — Minneapolis
- University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics — Philadelphia
Germany · 3 centers
- Justus-Liebig Universität - Department of Ophthalmology — Giessen
- Klinikum der Ludwig-Maximilian Universität München — München
- University of Tuebingen - Inst. for Ophthalmic Research — Tübingen
Brazil · 2 centers
- INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte — Belo Horizonte
- Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP) — São Paulo
Canada · 2 centers
- University of Alberta — Edmonton
- The Hospital for Sick Children - SickKids — Toronto
Belgium · 1 center
- Universitair Ziekenhuis Gent (UZ) — Ghent
France · 1 center
- Centre de maladies rares CHNO des Quinze Vingt — Paris
Netherlands · 1 center
- Radboud Universitair Medisch Centrum — Nijmegen
Spain · 1 center
- Hospital Sant Joan de Déu (SJD Barcelona Children's Hospital) — Barcelona
United Kingdom · 1 center
- Moorfields Eye Hospital NHS Foundation Trust — London
Identifiers
NCT: NCT06891443 · SB-110-007 · 2024-518378-14-00