Clinical trial NCT06891443: Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Leber Congenital Amaurosis 10
Blindness
Leber Congenital Amaurosis
Sensation Disorders
Vision Disorder
Neurological Manifestations
Eye Diseases, Hereditary
Eye Diseases
Eye Disorders Congenital
Retinal Disease
Keywords: LCA10
p.Cys998X
Antisense oligonucleotides
RNA therapy
QR-110
sepofarsen
CEP290
Leber's Congenital Amaurosis
c.2991+1655A&gt;G
Lead sponsor: Laboratoires Thea
Sponsor class: INDUSTRY
Collaborators: name: Sepul Bio
First posted: 2025-03-24
Enrollment: 32
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Paired-eye design.
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility 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 or stem-cell therapy for ocular or non-ocular disease.

Primary outcomes:
measure: Change from baseline in Best-Corrected Visual Acuity (BCVA)
timeFrame: 12 Months
Secondary outcomes:
measure: Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
timeFrame: Month 12
measure: 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)
timeFrame: Month 12
measure: Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
timeFrame: Month 12
measure: Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF
timeFrame: Month 12
measure: 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)
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: 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.
timeFrame: Month 12
measure: Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age
timeFrame: Month 12
measure: Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age
timeFrame: Month 12
measure: Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age
timeFrame: Month 12
measure: Change from baseline in eye-specific Patient Global Impression of Severity (PGI-S) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
timeFrame: Month 12
measure: Change from baseline in Best-Corrected Visual Acuity (BCVA) based on the ETDRS or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
timeFrame: Month 12
measure: Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)
timeFrame: Month 12
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Medical School
state: Minnesota
city: Philadelphia
country: United States
facility: University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics
state: Pennsylvania
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
Study officials:
References: