Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene

NCT06627179 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: SB-421a-0062024-515199-10-00
• Study Type: interventional
• Target: 81
• Locations: 10 countries
• Sites: 27

Brief Summary

The purpose of this Phase 2b study is to evaluate the safety and tolerability of ultevursen administered via intravitreal injection (IVT) in subjects with Retinitis Pigmentosa (RP) due to mutations in exon 13 of the USH2A gene. This is a multicenter Double-masked, Randomized, Sham-controlled study which will enroll 81 subjects.

Conditions

Retinitis Pigmentosa (RP); Usher Syndrome Type 2; Deaf Blind; Retinal Disease; Eye Diseases, Hereditary; Eye Disorders Congenital; Vision Disorders

Keywords

Retinitis Pigmentosa; Usher Syndrome Type 2; Deaf Blind; USH2A; RP; Exon 13; RNA therapies; antisense oligonucleotide; exon skipping; LUNA; IVT; NSRP

Outcome Measures

Primary Outcomes (1)

• To evaluate efficacy after 24 months of treatment

  Annualized percent change from baseline in ellipsoid zone (EZ) width as measured by spectral-domain optical coherence tomography (SD-OCT) up to Month 24.

  24 Months

Secondary Outcomes (10)

• Annualized change from baseline in static perimetry (SP) mean sensitivity

  Month 24

• Annualized change from baseline in microperimetry (MP) mean sensitivity

  Month 24

• Change from baseline in low luminance visual acuity (LLVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart

  Month 24

• Change from baseline in best-corrected visual acuity (BCVA) using the ETDRS chart

  Month 24

• Percent change from baseline in EZ area by SD-OCT

  Month 24

Study Arms (2)

Ultevursen 180/60 μg

EXPERIMENTAL

Subjects will receive an intravitreal injection (IVT) of ultevursen with concentrations of 3.6 mg/mL for initial dose and 1.2 mg/mL for maintenance doses every 6 months thereafter through Month 18 (up to 4 doses).

Drug: Intravitreal Injection of Ultevursen

Sham Procedure

SHAM COMPARATOR

Sham-procedure (no experimental drug administered)

Other: No intervention, will not receive any active study intervention

Interventions

Intravitreal Injection of Ultevursen DRUG

Up to 4 doses over a 24-month period

Ultevursen 180/60 μg

No intervention, will not receive any active study intervention OTHER

Sham-procedure (no experimental drug administered)

Sham Procedure

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• An adult (≥18 years) willing and able to provide informed consent for participation prior to performing any study related procedures
• OR A minor (8 to \<18 years) able to provide age-appropriate assent for study participation with a parent or legal guardian willing and able to provide written permission for the subject's participation prior to performing any study related procedures. An adult willing to comply with the protocol, follow study instructions, attend study visits as required and willing and able to complete all study assessments, in the opinion of the Investigator.
• OR A minor able to complete all study assessments and comply with the protocol and has a parent or caregiver willing and able to follow study instructions and attend study visits with the subject as required, in the opinion of the Investigator.
• Both eyes exhibit clinical presentation consistent with RP involving Usher syndrome type 2 or NSRP based on ophthalmic, audiologic, or vestibular examinations. At screening, the Investigator will make the clinical diagnosis of "Usher syndrome type 2a," defined as RP with congenital hearing loss, or "non-syndromic RP," defined as RP without congenital hearing loss.
• A molecular diagnosis of biallelic disease causing variants (pathogenic or likely pathogenic) in the USH2A gene where at least one of the variants is located on exon 13. A historic genotyping report from a certified laboratory is acceptable with Sponsor approval.
• Clearly visible and measurable SD-OCT horizontal EZ width of ≥2.2 mm in both eyes based on the assessment of the CRC.
• BCVA ≥55 letters based on ETDRS (equivalent to 20/80 based on Snellen notation, or logarithm of the minimum angle of resolution \[logMAR\] +0.6) in both eyes.
• Impairment of VF as assessed by SP with a mean sensitivity greater than 4 decibels (dB) and less than 25 dB measured by a V target size in the TE at screening.
• Mean sensitivity greater than 2 dB as determined by MP in the TE at screening.
• Symmetry of baseline disease in both eyes, defined as the mean BCVA (based on ETDRS) of one eye within ≤10 letters of the mean BCVA of the other eye at screening.

You may not qualify if:

• Presence of additional non-exon 13 USH2A pathogenic or likely pathogenic variant on the USH2A allele carrying the exon 13 mutation in subjects who have one exon 13 disease causing variant and one non-exon 13 disease causing variant.
• Presence of additional non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations.
• At screening, the EZ horizontal or vertical width are outside the field of the SD-OCT scan based on the assessment of the CRC.
• Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator may either put the subject at risk because of participation in the study, may impact the subject's ability to participate in the study, or may interfere with assessment of efficacy and safety in the study.
• Any intraocular surgery within 3 months of study entry or any planned intraocular or peri-ocular surgery during the study. Subjects may be eligible after 3 months post-surgery as long as they have fully recovered, in the opinion of the Investigator.
• Receipt of any IVT injection prior to study entry.

Sponsors & Collaborators

• Laboratoires Thea: lead
• Sepul Bio: collaborator

Study Sites (27)

The University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Bascom Palmer Eye Institute/University of Miami

Miami, Florida, 33136, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Massachusetts Eye and Ear

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan- Kellogg Eye Center

Ann Arbor, Michigan, 48105, United States

RECRUITING

Duke Eye Center

Durham, North Carolina, 27705, United States

RECRUITING

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, 75231, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

University of Wisconsin- Madison

Madison, Wisconsin, 53705, United States

RECRUITING

Ghent University Hospital

Ghent, B-9000, Belgium

RECRUITING

Federal University of São Paulo - Hospital São Paulo (UNIFESP-HSP)

São Paulo, 04021-001, Brazil

RECRUITING

Hospital for Sick Children

Toronto, Ontario, M5G1E8, Canada

RECRUITING

McGill University Health Centre for Innovative Medicine

Montreal, Quebec, H4A3J1, Canada

RECRUITING

Rigshospitalet and University of Copenhagen

Glostrup Municipality, 2600, Denmark

RECRUITING

Hôpital Gui de Chauliac - CHRU de Montpellier - Maladies Sensorielles Génétique

Montpellier, 34295, France

RECRUITING

Centre de maladies rares CHNO des Quinze Vingt

Paris, 75012, France

RECRUITING

Universitätsklinikum Tübingen

Tübingen, 72076, Germany

RECRUITING

ASST Santi Paolo e Carlo Hospital, University of Milan

Milan, 20142, Italy

RECRUITING

AOU Università degli Studi della Campania Luigi Vanvitelli

Naples, 80131, Italy

NOT YET RECRUITING

Amsterdam University Medical Center - Locatie AMC

Amsterdam, 1105 AZ, Netherlands

RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

RECRUITING

Het Oogziekenhuis Rotterdam

Rotterdam, 3011 BH, Netherlands

RECRUITING

Oxford Eye Hospital

Headington, Oxford, OX3 9DU, United Kingdom

RECRUITING

University of Edinburgh / NHS Lothian

Edinburgh, EH39HA, United Kingdom

RECRUITING

Moorfields Eye Hosptial

London, EC1V 2PD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Retinitis Pigmentosa; Usher Syndromes; Retinal Diseases; Eye Diseases, Hereditary; Eye Abnormalities; Vision Disorders

Condition Hierarchy (Ancestors)

Eye Diseases; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Deaf-Blind Disorders; Deafness; Hearing Loss; Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Hearing Loss, Sensorineural; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Blindness; Abnormalities, Multiple; Congenital Abnormalities; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Sepul Bio Advocacy Director

CONTACT

+31 617060791; contact@sepulbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2024
• First Posted: October 4, 2024
• Study Start: December 11, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); BR (1); FR (2); DK (1); GB (3); IT (2); US (11); CA (2); DE (1); BE (1)