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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Eye Diseases; Eye Diseases, Hereditary; Sensation Disorders; Blindness; Leber Congenital Amaurosis; Leber Congenital Amaurosis 10; Retinal Disease; Eye Disorders Congenital; Neurological Manifestations; Vision Disorder
• Intervention / Treatment: Drug: sepofarsen; Other: Placebo IVT

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.

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sepul Bio Patient Advocacy Director; Phone Number: +31 617060791; Email: contact@sepulbio.com
• Study Contact Backup: Name: Sepul Bio Chief Medical Officer

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent (UZ)
• Brazil
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150270
      • Recruiting
      • INRET Clínica/ Santa Casa de Misericórdia de Belo Horizonte
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04023-062
      • Recruiting
      • Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • Recruiting
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M5G 2L3
      • Recruiting
      • The Hospital for Sick Children - SickKids
• France
  • Paris, France, 75012
    • Recruiting
    • Centre de maladies rares CHNO des Quinze Vingt
• Germany
  • Giessen, Germany, 35392
    • Recruiting
    • Justus-Liebig Universität - Department of Ophthalmology
  • München, Germany, 81377
    • Recruiting
    • Klinikum der Ludwig-Maximilian Universität München
  • Tübingen, Germany, 72076
    • Recruiting
    • University of Tuebingen - Inst. for Ophthalmic Research
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud Universitair Medisch Centrum
• United Kingdom
  • London, United Kingdom, EC1V 2PD
    • Recruiting
    • Moorfields Eye Hospital NHS Foundation Trust
• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • UCSF Wayne and Gladys Valley Center for Vision
  • Florida
    • Miami, Florida, United States, 33156
      • Recruiting
      • University of Miami - Bascom Palmer Eye Institute
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota Medical School
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sepofarsen - Treatment Eye - up to Month 12; Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.	Drug: sepofarsen; RNA antisense oligonucleotide for intravitreal injection; Other Names: QR-110
Placebo Comparator: Placebo - Fellow Eye - up to Month 12; Subjects to receive Sepofarsen in one eye (160µg first then 40µg) and Placebo in the fellow eye at baseline and at month 6.	Other: Placebo IVT; Placebo with identical appearance to sepofarsen
Active Comparator: Continued - Treatment Eye - up to Month 24; Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.	Drug: sepofarsen; RNA antisense oligonucleotide for intravitreal injection; Other Names: QR-110
Placebo Comparator: Continued - Fellow Eye - up to Month 24; Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.	Other: Placebo IVT; Placebo with identical appearance to sepofarsen
Active Comparator: Mixed - Treatment Eye - up to Month 24; Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.	Drug: sepofarsen; RNA antisense oligonucleotide for intravitreal injection; Other Names: QR-110
Active Comparator: Mixed - Fellow Eye - Month 12 to Month 24; Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18.	Drug: sepofarsen; RNA antisense oligonucleotide for intravitreal injection; Other Names: QR-110
Placebo Comparator: Mixed - Fellow Eye - up to Month 12; Subjects to receive Sepofarsen (40µg) in one eye and Sepofarsen in the fellow eye (160µg first then 40µg) at Month 12 and at Month 18 Note: up to Month 12 these subjects receive placebo in the Fellow Eye, as all subjects do.	Other: Placebo IVT; Placebo with identical appearance to sepofarsen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Low Luminance Visual Acuity (LLVA) based on FrACT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)		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)		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).	Month 12
Change from baseline in Contrast Sensitivity (CS) between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs) based on qCSF		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)		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.		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.		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.		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.		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.		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.		Month 12
Change from baseline in the Michigan Retinal Degeneration Questionnaire (MRDQ) score for subjects ≥ 13 years of age		Month 12
Change from baseline in the Michigan Vision-Related Anxiety Questionnaire (MVAQ) score for subjects ≥ 13 years of age		Month 12
Change from baseline in the Pediatric Eye Questionnaire (PedEyeQ) score for subjects < 13 years of age		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).	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	The multimodal assessment is based on a combination of visual acuity, retinal sensitivity, CS, functional vision, and/or PRO	Month 12
Change from baseline in Best-Corrected Visual Acuity (BCVA) based on the ETDRS and/or the BRVT between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)		Month 12
Change from baseline in Low Luminance Visual Acuity (LLVA) based on the ETDRS between Treatment Eyes (TEs) and Placebo Control Eyes (PCEs)		Month 12

Collaborators and Investigators

• Sponsor: Laboratoires Thea
• Collaborators: Sepul Bio

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: February 3, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 24, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: CEP290; LCA10; p.Cys998X; c.2991+1655A>G; Leber's Congenital Amaurosis; RNA therapy; QR-110; sepofarsen; Antisense oligonucleotides
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Optic Nerve Diseases; Cranial Nerve Diseases; Mitochondrial Diseases; Optic Atrophies, Hereditary; Optic Atrophy; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Neurologic Manifestations; Retinal Diseases; Eye Diseases; Sensation Disorders; Blindness; Vision Disorders; Eye Diseases, Hereditary; Eye Abnormalities; Leber Congenital Amaurosis; Optic Atrophy, Hereditary, Leber; Leber Congenital Amaurosis 10; Meckel Syndrome, Type 4
• Other Study ID Numbers: SB-110-007; 2024-518378-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No