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

NCT06891443 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: SB-110-0072024-518378-14-00
• Study Type: interventional
• Target: 32
• Locations: 7 countries
• Sites: 14

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.

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>G

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (18)

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

  Month 12

• 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

• 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

Study Arms (7)

Sepofarsen - Treatment Eye - up to Month 12

ACTIVE COMPARATOR

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

Placebo - Fellow Eye - up to Month 12

PLACEBO COMPARATOR

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

Continued - Treatment Eye - up to Month 24

ACTIVE COMPARATOR

Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

Drug: sepofarsen

Continued - Fellow Eye - up to Month 24

PLACEBO COMPARATOR

Subjects to receive Sepofarsen (40µg) in one eye and Placebo in the fellow eye at Month 12 and Month 18.

Other: Placebo IVT

Mixed - Treatment Eye - up to Month 24

ACTIVE COMPARATOR

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

Mixed - Fellow Eye - Month 12 to Month 24

ACTIVE COMPARATOR

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

Mixed - Fellow Eye - up to Month 12

PLACEBO COMPARATOR

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

Interventions

sepofarsen DRUG

RNA antisense oligonucleotide for intravitreal injection

Also known as: QR-110

Continued - Treatment Eye - up to Month 24; Mixed - Fellow Eye - Month 12 to Month 24; Mixed - Treatment Eye - up to Month 24; Sepofarsen - Treatment Eye - up to Month 12

Placebo IVT OTHER

Placebo with identical appearance to sepofarsen

Continued - Fellow Eye - up to Month 24; Mixed - Fellow Eye - up to Month 12; Placebo - Fellow Eye - up to Month 12

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Laboratoires Thea: lead
• Sepul Bio: collaborator

Study Sites (14)

UCSF Wayne and Gladys Valley Center for Vision

San Francisco, California, 94158, United States

RECRUITING

University of Miami - Bascom Palmer Eye Institute

Miami, Florida, 33156, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

University of Minnesota Medical School

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Pennsylvania - Center for Advanced Retinal & Ocular Therapeutics

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Universitair Ziekenhuis Gent (UZ)

Ghent, 9000, Belgium

RECRUITING

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

RECRUITING

The Hospital for Sick Children - SickKids

Toronto, Ontario, M5G 2L3, Canada

RECRUITING

Centre de maladies rares CHNO des Quinze Vingt

Paris, 75012, France

RECRUITING

Justus-Liebig Universität - Department of Ophthalmology

Giessen, 35392, Germany

RECRUITING

Klinikum der Ludwig-Maximilian Universität München

München, 81377, Germany

RECRUITING

University of Tuebingen - Inst. for Ophthalmic Research

Tübingen, 72076, Germany

RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

RECRUITING

Moorfields Eye Hospital NHS Foundation Trust

London, EC1V 2PD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Leber Congenital Amaurosis 10; Blindness; Leber Congenital Amaurosis; Sensation Disorders; Vision Disorders; Neurologic Manifestations; Eye Diseases, Hereditary; Eye Diseases; Eye Abnormalities; Retinal Diseases; Meckel Syndrome, Type 4; Optic Atrophy, Hereditary, Leber

Condition Hierarchy (Ancestors)

Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Congenital Abnormalities; Optic Atrophies, Hereditary; Optic Atrophy; Optic Nerve Diseases; Cranial Nerve Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Sepul Bio Patient Advocacy Director

CONTACT

+31 617060791; contact@sepulbio.com

Sepul Bio Chief Medical Officer

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Paired-eye design.

Study Record Dates

• First Submitted: February 3, 2025
• First Posted: March 24, 2025
• Study Start: June 4, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); NL (1); GB (1); US (5); FR (1); DE (3); BE (1)