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

NCT ID: NCT06627179

Last Updated: 2026-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

81 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-11

Study Completion Date

2027-12-31

Brief Summary

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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.

Detailed Description

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A total of eighty-one (81) RP subjects will be enrolled in this study, randomized in a 2:1 ratio to either ultevursen or sham procedure, respectively. Subjects randomized to the active treatment group will receive therapy with ultevursen administered via intravitreal (IVT) injection to the treatment eye (TE) on Day 1 and at Months 6, 12, and 18. Subjects randomized to sham will undergo a sham procedure in the TE at the corresponding timepoints.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Ultevursen 180/60 μg

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).

Group Type EXPERIMENTAL

Intravitreal Injection of Ultevursen

Intervention Type DRUG

Up to 4 doses over a 24-month period

Sham Procedure

Sham-procedure (no experimental drug administered)

Group Type SHAM_COMPARATOR

No intervention, will not receive any active study intervention

Intervention Type OTHER

Sham-procedure (no experimental drug administered)

Interventions

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Intravitreal Injection of Ultevursen

Up to 4 doses over a 24-month period

Intervention Type DRUG

No intervention, will not receive any active study intervention

Sham-procedure (no experimental drug administered)

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. An adult (≥18 years) willing and able to provide informed consent for participation prior to performing any study related procedures
2. 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.
3. 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.
4. 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.
5. Clearly visible and measurable SD-OCT horizontal EZ width of ≥2.2 mm in both eyes based on the assessment of the CRC.
6. 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.
7. 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.
8. Mean sensitivity greater than 2 dB as determined by MP in the TE at screening.
9. 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.

Exclusion Criteria

1. 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.
2. Presence of additional non-exon 13 USH2A pathogenic mutation(s) on both USH2A alleles in subjects who have biallelic exon 13 mutations.
3. Presence of pathogenic or likely pathogenic variants in genes (other than the USH2A gene) which are known to be associated with other inherited retinal degenerative diseases or syndromes. Specifically, the presence of homozygous or compound heterozygous known disease-causing mutations in other genes involved in recessive retinal dystrophies, or the confirmed presence of a known single disease-causing variant in genes involved in dominant, X-linked, or mitochondrial retinal dystrophy genes is exclusionary.
4. At screening, the EZ horizontal or vertical width are outside the field of the SD-OCT scan based on the assessment of the CRC.
5. 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.
6. Presence of unstable concurrent cystoid macular edema (CME), or subject started on (or changed dose of) any medication for CME in the 3 months prior to enrollment. CME is allowed if stable for 3 months (with or without treatment). However, stable CME that disrupts the EZ width measurement, as determined by CRC, is an exclusion.
7. 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.
8. Receipt of any IVT injection prior to study entry.
Minimum Eligible Age

8 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sepul Bio

INDUSTRY

Sponsor Role collaborator

Laboratoires Thea

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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The University of California, San Francisco

San Francisco, California, United States

Site Status RECRUITING

Bascom Palmer Eye Institute/University of Miami

Miami, Florida, United States

Site Status RECRUITING

Emory University

Atlanta, Georgia, United States

Site Status RECRUITING

Massachusetts Eye and Ear

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan- Kellogg Eye Center

Ann Arbor, Michigan, United States

Site Status RECRUITING

Casey Eye Institute, Oregon Health & Science University

Portland, Oregon, United States

Site Status RECRUITING

University of Pennsylvania, Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Retina Foundation of the Southwest

Dallas, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

University of Wisconsin- Madison

Madison, Wisconsin, United States

Site Status RECRUITING

Ghent University Hospital

Ghent, , Belgium

Site Status RECRUITING

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

São Paulo, , Brazil

Site Status RECRUITING

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status RECRUITING

McGill University Health Centre for Innovative Medicine

Montreal, Quebec, Canada

Site Status RECRUITING

Rigshospitalet and University of Copenhagen

Glostrup Municipality, , Denmark

Site Status RECRUITING

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

Montpellier, , France

Site Status RECRUITING

Centre de maladies rares CHNO des Quinze Vingt

Paris, , France

Site Status RECRUITING

Universitätsklinikum Tübingen

Tübingen, , Germany

Site Status RECRUITING

ASST Santi Paolo e Carlo Hospital, University of Milan

Milan, , Italy

Site Status RECRUITING

AOU Università degli Studi della Campania Luigi Vanvitelli

Napoli, , Italy

Site Status NOT_YET_RECRUITING

Amsterdam University Medical Center - Locatie AMC

Amsterdam, , Netherlands

Site Status RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Site Status RECRUITING

Het Oogziekenhuis Rotterdam

Rotterdam, , Netherlands

Site Status RECRUITING

Oxford Eye Hospital

Headington, Oxford, United Kingdom

Site Status RECRUITING

University of Edinburgh / NHS Lothian

Edinburgh, , United Kingdom

Site Status RECRUITING

Moorfields Eye Hosptial

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Belgium Brazil Canada Denmark France Germany Italy Netherlands United Kingdom

Central Contacts

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Sepul Bio Advocacy Director

Role: CONTACT

+31 617060791

Other Identifiers

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2024-515199-10-00

Identifier Type: CTIS

Identifier Source: secondary_id

SB-421a-006

Identifier Type: -

Identifier Source: org_study_id

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