A dose-ranging randomized, open-label study evaluating the effect of bilateral intravitreal injection of GS010 at two dose levels on visual acuity and retinal mitochondrial activity in patients affected with ND4 Leber Hereditary Optic Neuropathy – The REVISE Study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gensight Biologics

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

20 Jan 2026 → ongoing

Decision date (initial)

2025-12-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

GenSight Biologics

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To assess the efficacy of bilateral GS010 IVT administered in patients with ND4-LHON, by determining the BCVA change from baseline to 1.5 years post-treatment in the study eyes at two different doses.

Secondary objectives 4

1. To assess the efficacy of bilateral GS010 IVT, by determining the BCVA responder rates from baseline to 1.5 years post-treatment in the study eyes at two different doses.
2. To assess the efficacy of bilateral GS010 IVT, by determining the BCVA change from baseline to 1.5 years post-treatment in both eyes at two different doses.
3. To assess the efficacy of bilateral GS010 IVT according to dose levels, by comparing the BCVA change from baseline to 1.5 years post-treatment in the study eyes of ARM H versus ARM L.
4. To assess the safety and tolerability of bilateral IVT of GS010 at two different doses.

Conditions and MedDRA coding

Leber Hereditary Optic Neuropathy due to mutations in the mitochondrial NADH Dehydrogenase 4 gene

Regulatory references

Scientific advice from competent authorities

Agence Nationale De Sante Publique

EMA paediatric investigation plan (PIP)

EMEA-001992-PIP02-16

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Aged 15 years or older at the time of vision loss onset
2. Clinically manifested vision loss due to ND4 LHON in both eyes
3. BCVA of at least LogMAR +2.39, measured at the FrACT scale, in both eyes
4. Documented results of genotyping showing the presence of pathogenic LHON-associated mutation(s) in the ND4 mitochondrial gene and the absence of other pathogenic LHON-associated mutations in the patient’s mitochondrial DNA; absence of pathogenic mutations, other than the ND4 LHON-causing mutation(s), which are known to cause pathology of the optic nerve, retina or afferent visual system. Historic results of genetic analysis are acceptable upon Sponsor approval.
5. Vision loss duration from 6 months to 1.5 years in the first affected eye at the Inclusion visit (Day -1)
6. No limitations to OCT image collection that would prevent high quality, reliable images from being obtained in both eyes, as determined by the reading center
7. Clear ocular media and adequate pupillary dilation to permit thorough ocular examination, as assessed by the Investigator
8. Human immunodeficiency virus (HIV) negative serology
9. Female patients of childbearing potential must agree to use effective methods of birth control for up to 6 months after Treatment visit (Day 0). Male patients must agree to use condoms with their female partners for up to 6 months after Treatment visit (Day 0).
10. Willing and able to comply with the protocol, follow study instructions, attend study visits as required and complete all study assessments
11. Patient – and parent/legal guardian if the patient is under 18 years of age – has provided signed, written informed consent

Exclusion criteria 12

1. Any known allergy or hypersensitivity to GS010 or any of its constituents
2. Contraindication to IVT in any eye according to the Investigator’s clinical judgment and international guidelines (Avery, 2014)
3. Prior intraocular surgery or procedure or IVT, which occurred 6 months prior to inclusion and is considered of clinical relevance per Investigator assessment, or planned intraocular surgery or procedure
4. Presence of optic neuropathy from any cause except LHON, as determined by the Investigator
5. History of recurrent uveitis (idiopathic or immune-related) or active intraocular inflammation, as determined by the Investigator
6. Indication of a unilateral treatment with GS010, as determined by the Investigator: • Unilateral or asymmetric ND4 LHON disease: only one eye affected with a vision loss due to ND4 LHON, and the fellow eye with preserved BCVA (LogMAR 0 or close to 0); • Amblyopia: unilateral treatment of the functional eye with a vision loss due to ND4 LHON; • Patient’s desire for unilateral treatment
7. Ingestion of idebenone less than 7 days prior to the Inclusion visit (Day -1)
8. Inability to tolerate the anti-inflammatory regimen
9. Presence of ocular disease (excluding LHON), or systemic disease, or condition (including medications and laboratory test abnormalities) that could compromise patient safety or interfere with assessment of efficacy and safety, as determined by the Investigator
10. Use of any investigational drug, or device, within 90 days, or 5 half-lives, preceding the Inclusion visit (Day-1), whichever is longer, or plans to participate in another study of an investigational drug or device during the study period
11. Previous treatment with ocular gene therapy in either eye.
12. Pregnancy or breast-feeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. BCVA change from baseline to 1.5 years post-treatment in the study eyes.

Secondary endpoints 6

1. BCVA responder rates from baseline to 1.5 years post-treatment in the study eyes, defined as an improvement of at least -0.2 LogMAR.
2. BCVA change from baseline to 1.5 years post-treatment in both eyes.
3. Difference between ARM H and ARM L in BCVA change from baseline to 1.5 years post-treatment in the study eyes.
4. Frequency and severity of ocular adverse events (AEs).
5. Frequency and severity of ocular AEs of special interest (AESIs) post-GS010 administration: o Intraocular inflammation; evolution with time and response to corticosteroid. o Increase in intraocular pressure (IOP); evolution with time and response to IOP lowering treatment.
6. Frequency and severity of non-ocular AEs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gensight Biologics

Sponsor organisation

Gensight Biologics

Address

74 Rue Du Faubourg Saint Antoine

City

Paris

Postcode

75012

Country

France

Scientific contact point

Organisation

Gensight Biologics

Contact name

Magali Gibou

Public contact point

Organisation

Gensight Biologics

Contact name

Clinics Gensight Biologics

Third parties 11

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications