Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)

Phase 3RecruitingNCT06891443

Laboratoires Thea32 enrolled

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Leber Congenital Amaurosis 10 Blindness Leber Congenital Amaurosis

Eligibility

Sex: ALLMin age: 6 Years

Medical Language ↔ Plain English

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.

Locations (13)

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

...and 3 more locations

Outcomes

Primary Outcomes

Change from baseline in Best-Corrected Visual Acuity (BCVA)

Change from baseline in BCVA based on the Freiburg Acuity and Contrast Test (FrACT) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)

Time frame: 12 Months

Secondary Outcomes

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

Eye-specific Patient Global Impression of Change (PGI-C) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)

PGI-C (PATIENT GLOBAL IMPRESSION OF CHANGE ) assesses a patient's perception of overall change in their vision in the respective eye over time. The minimum score (best outcome) is 1 ("Very Much Better") and the maximum score (worst outcome) is 7 ("Very Much Worse"). Higher scores indicate a worse health outcome (greater worsening).

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

Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age

Time frame: Month 12

Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age

Time frame: Month 12

Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age

Time frame: Month 12

Change from baseline in eye-specific Patient Global Impression of Severity (PGI-S) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)

PGI-S (PATIENT GLOBAL IMPRESSION OF SEVERITY ) assesses a patient's perception of severity of their eye condition in the respective eye over the past week. The minimum score (best outcome) is 1 ("None") and the maximum score (worst outcome) is 5 ("Very Severe"). Higher scores indicate a worse health outcome (greater severity).

Time frame: Month 12

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)

Time frame: Month 12

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)

Time frame: Month 12

Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts