Optic, Atrophy, Hereditary, LeberPhase 3REVERSENCT02652780
Efficacy Study of GS010 for Treatment of Vision Loss From 7 Months to 1 Year From Onset in LHON Due to the ND4 Mutation (REVERSE)
A Phase 3 study testing GS010 in people with Optic, Atrophy, Hereditary, Leber, run by GenSight Biologics at 7 sites in 5 countries.
Trial summary
The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Optic, Atrophy, Hereditary, Leber
- What is being tested?
- GS010
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Jan 2016to Dec 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Selection Criteria:
- Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.
- Age 15 years or older.
- Onset of vision loss based on medically documented history or participants testimony, in both eyes for 181 and ≤365 days in duration.
- Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance.
- Female participants (if of childbearing potential) must agree to use effective methods of birth control up to 6 months after IVT injection and male participants must agree to use condoms for up to 6 months after IVT injection.
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- Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
- Signed written informed consent.
- Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2).
- Documented results of genotyping showing the presence of the G11778A mutation in the ND4 gene and the absence of the other primary LHON-associated mutations (ND1 or ND6) in the participant's mitochondrial DNA.
- Review of all selection criteria to ensure continued compliance.
- Have a negative test for infection with human immunodeficiency virus (HIV).
- Have a negative pregnancy test for women of childbearing potential (a woman who is two years post-menopausal or surgically sterile is not considered to be of childbearing potential).
Who cannot join
- Non-Selection Criteria:
- Participants who meet at least one of the following criteria at the Screening Visit (Visit 1) will not be included into the study.
- Any known allergy or hypersensitivity to GS010 or its constituents.
- Contraindication to IVT injection.
- IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1).
- Previous vitrectomy in either eye.
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- Narrow angle in either eye contra-indicating pupillary dilation.
- Presence of disorders of the ocular media, such as the cornea and lens, which may interfere with visual acuity and other ocular assessments during the study period.
- Vision disorders, other than LHON, involving visual disability or with the potential to cause further vision loss during the trial period.
- Causes of optic neuropathy other than LHON and glaucoma.
- Participants with known mutations of other genes involved in pathological retinal or optic nerve conditions.
- Presence of ocular or systemic disease, other than LHON, whose pathology or associated treatments might affect the retina or the optic nerve.
- History of amblyopia associated with a Snellen visual acuity equivalent of worse than 20/80 (equivalent to 6/24 at 6 meters, decimal acuity 0.25, LogMAR +0.6) in the affected eye.
- Presence of ocular conditions, which in the opinion of the Investigator will prevent good quality SD-OCT imaging from being obtained.
- Presence, in either eye, of uncontrolled glaucoma, defined as an IOP greater than 25 mmHg, despite maximal medical therapy with intraocular pressure (IOP)-lowering agents.
- Active ocular inflammation or history of idiopathic or autoimmune-associated uveitis.
- Participants participating in another clinical trial and receiving an IMP within 90 days prior to the Screening Visit (Visit 1).
- Previous treatment with an ocular gene therapy product.
- Participants who have undergone ocular surgery of clinical relevance (per Investigator opinion) within 90 days preceding the Screening Visit (Visit 1).
- Female participants who are or who intend to breast feed during the trial period.
- Participants who meet at least one of the following criteria at the Inclusion Visit (Visit 2) will not be included in the study.
- Any non-selection criteria which may have appeared after the screening visit.
- Participants taking idebenone who have not completely discontinued the idebenone at least 7 days prior to Visit 2. If the participant has not discontinued idebenone at least 7 days prior to Visit 2, the visit may be delayed until the 7-day period is complete.
- Presence, at the time of study inclusion, of infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
- Presence of systemic illness, including alcohol and drug abuse (except nicotine), or medically significant abnormal laboratory values that are deemed by the Investigator to preclude the participant's safe participation in the study.
- Presence of illness or disease that, in the opinion of the Investigator, include symptoms and/or the associated treatments that can alter visual function, for instance cancers or pathology of the central nervous system.
- Any medical or psychological condition that, in the opinion of the Investigator, may compromise the safe participation of the participant in the study or would preclude compliance with the study protocol or ability of the participant to successfully complete the study.
- Participants unable or unwilling to comply with the protocol requirements.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
United States3 sites
Department of Ophthalmology, Emory University School of Medicine
Atlanta, Georgia, 30322
Doheny Eye Center, University of California, Los Angeles
Los Angeles, California
Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
France1 site
Centre National Hospitalier d'Ophtalmologie des Quinze-Vingt
Paris, Paris
Germany1 site
Department of Neurology, University of Munich, Friedrich-Baur-Institute
Munich, 80336
Italy1 site
IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria
Bologna, Bologna
United Kingdom1 site
Moorfields Eye Hospital NHS Foundation Trust
London, EC1V 2PD
About this study
Official title: Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene
The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year.
- Conditions
- Optic, Atrophy, Hereditary, Leber
- Being tested
- GS010, Sham Intravitreal Injection
- Keywords
- Leber Hereditary Optic Neuropathy, Leber Hereditary Optic Atrophy, Heredity Optic Atrophy, Eye Diseases, Hereditary Eye Diseases, Inborn Genetic Disease, Genetic Therapy, Intravitreal Injections, Mitochondrial Disease, AAV2 Vectors, Nervous System Diseases, Neurodegenerative Disease, Heredodegenerative Disorders of the Nervous System
- Medical subject headings
- Optic Atrophy, Hereditary, Leber, Eye Diseases, Eye Diseases, Hereditary, Genetic Diseases, Inborn, Mitochondrial Diseases, Nervous System Diseases, Neurodegenerative Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS010Biological
Also called Lenadogene Nolparvovec, rAAV2/2-ND4
Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant.
GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.
Sham Intravitreal InjectionDevice
Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant.
Sham-treated Eyes: One eye of each participant will undergo sham injection. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.
| Study group | Role | What they receive |
|---|---|---|
| GS010-treated Eyes | Experimental | Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®. Receives: Biological: GS010 |
| Sham-treated Eyes | Sham comparator | Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle. Receives: Device: Sham Intravitreal Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48
Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart.
1 ETDRS line = 5 letters
1 ETDRS line = 0.1 LogMAR
A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity.
Change = (Week 48 score - Baseline score).
Measured: Baseline and Week 48
Secondary outcomes (11)
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96
Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart.
1 ETDRS line = 5 letters
1 ETDRS line = 0.1 LogMAR
A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity.
Change = (Week 96 score - Baseline score).
Measured: Baseline and Week 96
Number of Eye Responders to Treatment at Week 48 and Week 96
An eye was determined as a responder to treatment based on 2 different definitions.
Definition 1: An eye responder was defined by an improvement of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity score of at least 15 letters compared to Baseline, or a final visual acuity greater than a Snellen acuity equivalent of 20/200 (a score of at least 1 letter).
Definition 2: An eye responder was defined by an improvement of the ETDRS score of at least 20 letters compared to Baseline.
Measured: Baseline; Week 48 and Week 96
Number of Subject Responders to Treatment at Week 48 and Week 96
A subject responder was defined as a participant whose Early Treatment Diabetic Retinopathy Study (ETDRS) score of the treated eye (that received GS010), was at least 15 letters better than the sham eye, or whose treated eye had a logarithm of the minimal angle of resolution (logMAR) acuity score of at least 0.3 logMAR better than the sham eye.
Measured: Week 48 and Week 96
Change From Baseline in GCL Macular Volume at Week 48 and Week 96
Ganglion cell layer (GCL) macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering).
Measured: Baseline and Week 48; Baseline and Week 96
Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96
Retinal nerve fiber layer (RNFL) temporal quadrant thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering).
Measured: Baseline and Week 48; Baseline and Week 96
Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96
Papillomacular bundle thickness was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering).
Measured: Baseline and Week 48; Baseline and Week 96
Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96
Early Treatment Diabetic Retinopathy Study (ETDRS) total macular volume was measured as a parameter of spectral domain-optical coherence tomography (SD-OCT). SD-OCT was obtained with the Spectralis® OCT (Heidelberg Engineering).
Measured: Baseline and Week 48; Baseline and Week 96
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96
The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of foveal threshold sensitivities. Foveal threshold sensitivity is measured in decibels (dB), which ranges from 0 dB to 50 dB. A sensitivity threshold of 0 dB indicates not being able to see the most intense perimetric stimulus, while higher dB indicates better/normal foveal vision. A positive change from baseline indicates an improvement of symptoms.
Measured: Baseline and Week 48; Baseline and Week 96
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96
The assessment of standardized automated visual fields was measured using the Humphrey Visual Field (HVF) Analyzer II. Automated visual fields included the assessment of the mean deviation (MD) in decibels (dB) of sensitivity.
Measured: Baseline, Week 48 and Week 96
Change From Baseline in Contrast Sensitivity at Week 48 and Week 96
The assessment of contrast sensitivity was measured using the Pelli-Robson chart. The chart uses letters arranged in groups whose contrast varies from high to low. Participants read the letters, starting with the highest contrast, until they are unable to read 2 or 3 letters in a single group. Each eye is assigned a score based on the contrast of the last group in which 2 or 3 letters were correctly read, ranging from 0 to 2.2 "log of contrast sensitivity" (LogCS) units. A score of 2.0 LogCS, represents a normal sensitivity contrast, and indicates the eye was able to detect 2 of the 3 letters with a contrast of 1 percent (contrast sensitivity = 100 percent or log 2). Scores less than 2.0 signify poorer contrast sensitivity. Pelli-Robson contrast sensitivity score of less than 1.5 is consistent with visual impairment and a score of less than 1.0 represents in visual disability. A positive change from baseline indicates improvement in symptoms.
Measured: Baseline and Week 48; Baseline and Week 96
Change From Baseline in Color Vision
The assessment of color vision was measured using the Farnsworth-Munsell 100-Hue Color Test. Each of the 4 trays consisted of 21 caps. Participants were asked to sort the randomly arranged caps following the hue order from the first to the last fixed caps. The total error score (TES) was derived by the frequency the caps were misplaced and the severity, or distance of the misplacement.
Errors were made whenever caps were misplaced from the correct order. Error scores were calculated according to the distance between any two caps. The error score for each individual cap was the sum of the difference between the number of that cap and the numbers of the cap adjacent to it, minus 2. TES was the total sum of the error scores of the entire set of caps.
The best possible score was 0 and there is no defined upper limit to the total error score range. A lower score indicates improved color discrimination ability. A negative change from baseline indicates an improvement in symptoms.
Measured: Baseline and Week 48; Baseline and Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2016 (estimated)
- Study startJan 2016
- Primary completionJan 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Optic, Atrophy, Hereditary, LeberStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- GenSight Biologics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Patrick Yu Wai Man, MDPhDFRCOpht, Principal investigator, Moorfields Eye Hospital NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02652780
- Sponsor's protocol ID
- GS-LHON-CLIN-03B
- Other IDs
- 2015-001266-26, 2015
- Acronym
- REVERSE
- Status last verified
- Feb 2026
- First submitted
- 7 Jan 2016
- Last updated
- 2 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30.
PubMed 36449262Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. eCollection 2021.
PubMed 34108929
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-Masked, Sham-Controlled Clinical Trial to Evaluate the Efficacy of a Single Intravitreal Injection of GS010 in Subjects Affected for More Than 6 Months and To 12 Months by LHON Due to the G11778A Mutation in the ND4 Gene
- ClinicalTrials.gov ID
- NCT02652780
- Acronym / sponsor ID
- REVERSE / GS-LHON-CLIN-03B
- Conditions
- Optic, Atrophy, Hereditary, Leber
- Keywords
- Leber Hereditary Optic Neuropathy, Leber Hereditary Optic Atrophy, Heredity Optic Atrophy, Eye Diseases, Hereditary Eye Diseases, Inborn Genetic Disease, Genetic Therapy, Intravitreal Injections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- GenSight BiologicsIndustry (pharma, biotech, devices)
- Study start
- Jan 2016 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 12 Jan 2016 (estimated)
- Results
- Posted 23 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to assess the effectiveness of GS010, a gene therapy, in improving the visual outcome in participants with Leber Hereditary Optic Neuropathy (LHON) due to the G11778A ND4 mitochondrial mutation when vision loss is present for more than six months and up to one year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GS010-treated Eyes | Experimental | Biological: GS010Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®. |
| Sham-treated Eyes | Sham comparator | Device: Sham Intravitreal InjectionEach participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle. |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.
- Age 15 years or older.
- Onset of vision loss based on medically documented history or participants testimony, in both eyes for 181 and ≤365 days in duration.
- Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance.
- Female participants (if of childbearing potential) must agree to use effective methods of birth control up to 6 months after IVT injection and male participants must agree to use condoms for up to 6 months after IVT injection.
Key exclusion criteria (28 listed)
- Participants who meet at least one of the following criteria at the Screening Visit (Visit 1) will not be included into the study.
- Any known allergy or hypersensitivity to GS010 or its constituents.
- Contraindication to IVT injection.
- IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1).
- Previous vitrectomy in either eye.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GS010Also: Lenadogene Nolparvovec, rAAV2/2-ND4Both eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®. | Biological | GS010-treated Eyes |
| Sham Intravitreal InjectionBoth eyes of each participant will receive standard antiseptic preparation, administration of topical local ocular anesthetic agents and will undergo pupillary dilation. Administration of an intra-ocular pressure lowering agent will precede treatment for every participant. Sham-treated Eyes: One eye of each participant will undergo sham injection. Sham Intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle. | Device | Sham-treated Eyes |
Primary outcome
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48
Time frame: Baseline and Week 48
Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. The visual acuity logarithm of the minimal angle of resolution (LogMAR) score was derived from the number of letters participants could read on the ETDRS chart. 1 ETDRS line = 5 letters 1 ETDRS line = 0.1 LogMAR A lower LogMAR score denotes better visual acuity and a negative change from baseline indicates an improvement in visual acuity. Change = (Week 48 score - Baseline score).
11 secondary outcomes
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96
Time frame: Baseline and Week 96
Number of Eye Responders to Treatment at Week 48 and Week 96
Time frame: Baseline; Week 48 and Week 96
Number of Subject Responders to Treatment at Week 48 and Week 96
Time frame: Week 48 and Week 96
Change From Baseline in GCL Macular Volume at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96
Time frame: Baseline, Week 48 and Week 96
Change From Baseline in Contrast Sensitivity at Week 48 and Week 96
Time frame: Baseline and Week 48; Baseline and Week 96
Change From Baseline in Color Vision
Time frame: Baseline and Week 48; Baseline and Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36449262Carelli V, Newman NJ, Yu-Wai-Man P, Biousse V, Moster ML, Subramanian PS, Vignal-Clermont C, Wang AG, Donahue SP, Leroy BP, Sergott RC, Klopstock T, Sadun AA, Rebolleda Fernandez G, Chwalisz BK, Banik R, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA; the LHON Study Group. Indirect Comparison of Lenadogene Nolparvovec Gene Therapy Versus Natural History in Patients with Leber Hereditary Optic Neuropathy Carrying the m.11778G>A MT-ND4 Mutation. Ophthalmol Ther. 2023 Feb;12(1):401-429. doi: 10.1007/s40123-022-00611-x. Epub 2022 Nov 30.
- Derived from this study: PubMed 34108929Newman NJ, Yu-Wai-Man P, Carelli V, Biousse V, Moster ML, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Girmens JF, La Morgia C, DeBusk AA, Jurkute N, Priglinger C, Karanjia R, Josse C, Salzmann J, Montestruc F, Roux M, Taiel M, Sahel JA. Intravitreal Gene Therapy vs. Natural History in Patients With Leber Hereditary Optic Neuropathy Carrying the m.11778G>A ND4 Mutation: Systematic Review and Indirect Comparison. Front Neurol. 2021 May 24;12:662838. doi: 10.3389/fneur.2021.662838. eCollection 2021.
- National Library of Medicine's Genetics Home Reference for Leber Hereditary Optic NeuropathyLink provided by the sponsor.
- National Library of Medicine's Genes and Gene TherapyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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A Phase 3, Multicenter, Randomized, Double-Masked, Sham-Controlled Clinical Trial for Leber's Hereditary Optic Neuropathy (LHON) Associated With ND4 Mutation
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Yu Wai Man, MDPhDFRCOpht principal investigator
Moorfields Eye Hospital NHS Foundation Trust
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GS010 in people with Optic, Atrophy, Hereditary, Leber, run by GenSight Biologics at 7 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, France, Germany, Italy, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48 (time frame: Baseline and Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02652780, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2026; AzTrials last refreshed its copy on 26 Oct 2026.