ClinicalTrials.gg
CompletedNCT02652780REVERSEUpdated Mar 2, 2026Results posted

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 interventional study of GS010 and Sham Intravitreal Injection in Optic, Atrophy, Hereditary, Leber, sponsored by GenSight Biologics. Completed at 7 sites in 5 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2026-03-02.

Sponsored by GenSight Biologics · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
37
Allocation
Randomized
Ages
15 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • 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
  • Mitochondrial Disease
  • AAV2 Vectors
  • Nervous System Diseases
  • Neurodegenerative Disease
  • Heredodegenerative Disorders of the Nervous System
03

In context

Optic Atrophy, Hereditary, Leber

44 studies on the registry are indexed under Optic Atrophy, Hereditary, Leber; 9 are open to participants now.

This study's enrollment of 37 is close to the median of 36 across 31 interventional studies indexed under Optic Atrophy, Hereditary, Leber.

Browse Optic Atrophy, Hereditary, Leber studies →

Lead sponsor

GenSight Biologics is the lead sponsor of 9 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
15 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

Selection Criteria:

Participants must meet all the following criteria at the Screening Visit (Visit 1) in order to be included into the study.

  1. Age 15 years or older.
  2. Onset of vision loss based on medically documented history or participants testimony, in both eyes for 181 and ≤365 days in duration.
  3. Each eye of the participant maintaining visual ability to allow at least for counting of the examiner's fingers at any distance.
  4. Female participants (if of ) must agree to use effective methods of up to 6 months after IVT injection and male participants must agree to use condoms for up to 6 months after IVT injection.
  5. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
  6. Signed written .

Inclusion Criteria:

Participants included in the study must satisfy all the following criteria at the Inclusion Visit (Visit 2).

  1. 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.
  2. Review of all selection criteria to ensure continued compliance.
  3. Have a negative test for infection with (HIV).
  4. Have a negative pregnancy test for women of childbearing potential (a woman who is two years or surgically sterile is not considered to be of childbearing potential).

Exclusion Criteria:

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.

  1. Any known allergy or to GS010 or its constituents.
  2. to IVT injection.
  3. IVT drug delivery to either eye within 30 days prior to the Screening Visit (Visit 1).
  4. Previous vitrectomy in either eye.
  5. Narrow angle in either eye contra-indicating pupillary dilation.
  6. 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.
  7. Vision disorders, other than LHON, involving visual disability or with the potential to cause further vision loss during the trial period.
  8. Causes of optic neuropathy other than LHON and glaucoma.
  9. Participants with known mutations of other genes involved in pathological retinal or optic nerve conditions.
  10. Presence of ocular or systemic disease, other than LHON, whose pathology or associated treatments might affect the retina or the optic nerve.
  11. 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.
  12. Presence of ocular conditions, which in the opinion of the Investigator will prevent good quality SD-OCT imaging from being obtained.
  13. 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.
  14. Active ocular inflammation or history of idiopathic or -associated uveitis.
  15. Participants participating in another clinical trial and receiving an IMP within 90 days prior to the Screening Visit (Visit 1).
  16. Previous treatment with an ocular gene therapy product.
  17. Participants who have undergone ocular surgery of clinical relevance (per Investigator opinion) within 90 days preceding the Screening Visit (Visit 1).
  18. Female participants who are or who intend to breast feed during the trial period.

Exclusion Criteria:

Participants who meet at least one of the following criteria at the Inclusion Visit (Visit 2) will not be included in the study.

  1. Any non-selection criteria which may have appeared after the screening visit.
  2. 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.
  3. Presence, at the time of study inclusion, of infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
  4. 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.
  5. 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.
  6. 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.
  7. Participants unable or unwilling to comply with the protocol requirements.
Terms in these criteria, in plain language(8)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
37 participants (actual)

Study arms

  • Experimental
    GS010-treated Eyes

    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®.

    Biological: GS010

  • Sham comparator
    Sham-treated Eyes

    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.

    Device: Sham Intravitreal Injection

Interventions

  • BiologicalGS010

    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®.

    Also known as: Lenadogene Nolparvovec, rAAV2/2-ND4

  • DeviceSham Intravitreal Injection

    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.

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Baseline and Week 48

Secondary outcomes

  1. 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).

    Time frame: Baseline and Week 96

  2. 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.

    Time frame: Baseline; Week 48 and Week 96

  3. 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.

    Time frame: Week 48 and Week 96

  4. 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).

    Time frame: Baseline and Week 48; Baseline and Week 96

  5. 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).

    Time frame: Baseline and Week 48; Baseline and Week 96

  6. 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).

    Time frame: Baseline and Week 48; Baseline and Week 96

  7. 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).

    Time frame: Baseline and Week 48; Baseline and Week 96

  8. 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.

    Time frame: Baseline and Week 48; Baseline and Week 96

  9. 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.

    Time frame: Baseline, Week 48 and Week 96

  10. 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.

    Time frame: Baseline and Week 48; Baseline and Week 96

  11. 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.

    Time frame: Baseline and Week 48; Baseline and Week 96

07

Results

Posted Jan 23, 2020

Participant flow

Participant flow — Overall Study
MilestoneAll Participants
Started37
Completed37
Not completed0

Outcome measures

PrimaryChange 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).

Time frame:
Baseline and Week 48
Reported as:
Least squares mean · LogMAR
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48
LogMARGS010-treated EyesSham-treated Eyes
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48-0.219 ± 0.055-0.211 ± 0.055
Statistical analysis
  • GS010-treated Eyes vs Sham-treated Eyes · ANCOVA · p = 0.8783 · Mean difference (net): -0.008 · 95% CI -0.119 to 0.102
SecondaryChange 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).

Time frame:
Baseline and Week 96
Reported as:
Least squares mean · LogMAR
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96
LogMARGS010-treated EyesSham-treated Eyes
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96-0.308 ± 0.068-0.259 ± 0.068
SecondaryNumber 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.

Time frame:
Baseline; Week 48 and Week 96
Reported as:
Count of units · Eyes
Number of Eye Responders to Treatment at Week 48 and Week 96
EyesGS010-treated EyesSham-treated Eyes
Definition 1: Week 4875
Definition 1: Week 96126
Definition 2: Week 481013
Definition 2: Week 961719
SecondaryNumber 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.

Time frame:
Week 48 and Week 96
Reported as:
Count of participants · Participants
Number of Subject Responders to Treatment at Week 48 and Week 96
ParticipantsAll Participants
Week 4837
Week 9637
SecondaryChange 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).

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Least squares mean · mm^3
Change From Baseline in GCL Macular Volume at Week 48 and Week 96
mm^3GS010-treated EyesSham-treated Eyes
Week 48-0.003 ± 0.012-0.038 ± 0.012
Week 96-0.018 ± 0.012-0.031 ± 0.012
SecondaryChange 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).

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Least squares mean · µm
Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96
µmGS010-treated EyesSham-treated Eyes
Week 48-0.562 ± 0.988-3.354 ± 1.017
Week 96-1.791 ± 0.974-2.042 ± 0.951
SecondaryChange 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).

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Least squares mean · µm
Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96
µmGS010-treated EyesSham-treated Eyes
Week 481.6 ± 1.3-1.0 ± 1.4
Week 961.2 ± 1.30.7 ± 1.3
SecondaryChange 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).

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Least squares mean · mm^3
Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96
mm^3GS010-treated EyesSham-treated Eyes
Week 48-0.104 ± 0.046-0.224 ± 0.046
Week 96-0.200 ± 0.037-0.265 ± 0.037
SecondaryChange 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.

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Mean · decibels (dB)
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96
decibels (dB)GS010-treated EyesSham-treated Eyes
Week 480.7 ± 8.9-0.5 ± 11.9
Week 961.3 ± 8.02.4 ± 10.8
SecondaryVisual 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.

Time frame:
Baseline, Week 48 and Week 96
Reported as:
Mean · decibels (dB)
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96
decibels (dB)GS010-treated EyesSham-treated Eyes
Baseline MD-25.99 ± 8.37-24.94 ± 9.70
Week 48 MD-22.83 ± 9.43-22.94 ± 9.80
Week 96 MD-23.22 ± 8.98-22.43 ± 9.39
SecondaryChange 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.

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Least squares mean · LogCS
Change From Baseline in Contrast Sensitivity at Week 48 and Week 96
LogCSGS010-treated EyesSham-treated Eyes
Week 480.19 ± 0.050.09 ± 0.05
Week 960.22 ± 0.060.12 ± 0.06
SecondaryChange 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.

Time frame:
Baseline and Week 48; Baseline and Week 96
Reported as:
Mean · score on a scale
Change From Baseline in Color Vision
score on a scaleGS010-treated EyesSham-treated Eyes
Week 48-30.0 ± 255.0-44.3 ± 182.2
Week 96-10.3 ± 247.3-61.0 ± 188.9

Adverse events

Collected over From first dose to end of study (a maximum of 96 weeks). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
All Participants0/37 (0%)3/37 (8.1%)37/37 (100%)
Most frequent serious events
Most frequent serious events
EventAll Participants
Acute myocardial infarctionCardiac disorders1/37
Retinal tearEye disorders1/37
Intestinal perforationGastrointestinal disorders1/37
DiverticulitisInfections and infestations1/37
Most frequent other events
Showing 10 of 30
Most frequent other events
EventAll Participants
IridocyclitisEye disorders15/37
Punctate keratitisEye disorders15/37
Autoimmune uveitisEye disorders14/37
Keratic precipitatesEye disorders13/37
Intraocular pressure increasedEye disorders11/37
Anterior chamber cellEye disorders9/37
Gamma-glutamyl transferase increasedInvestigations8/37
Vitreal cellsEye disorders7/37
Conjunctival haemorrhageEye disorders6/37
Conjunctival hyperaemiaEye disorders6/37

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)All Participants
<=18 years4
Between 18 and 65 years32
>=65 years1
Age, Continuous
Age, Continuous(years)All Participants
Mean34.2 ± 15.2
Sex: Female, Male
Sex: Female, Male(Participants)All Participants
Female8
Male29
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)All Participants
Region of Enrollment
Region of Enrollment(Participants)All Participants
United States20
United Kingdom2
France5
Germany6
Italy4
Weight
Weight(kilograms)All Participants
Mean80.1 ± 21.0
Height
Height(centimetres)All Participants
Mean174.4 ± 7.8
08

Study locations

7 sites
  • Doheny Eye Center, University of California, Los Angeles
    Los Angeles, California, United States
  • Department of Ophthalmology, Emory University School of Medicine
    Atlanta, Georgia 30322, United States
  • Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
  • Centre National Hospitalier d'Ophtalmologie des Quinze-Vingt
    Paris, Paris, France
  • Department of Neurology, University of Munich, Friedrich-Baur-Institute
    Munich, 80336, Germany
  • IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria
    Bologna, Bologna, Italy
  • Moorfields Eye Hospital NHS Foundation Trust
    London, EC1V 2PD, United Kingdom
09

References and documents

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 36449262 ↗
  • Newman 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 documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Jan 2016 to primary completion in Jan 2018, 24 months.

Results were first posted in Jan 2020, 2 years after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jan 7, 2016
First posted
Jan 12, 2016
StartActual
Jan 2016
Primary completionActual
Jan 2018
CompletionActual
Dec 2018
Results first posted
Jan 23, 2020
Last update
Mar 2, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Mar 2, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02652780
Lead sponsor
GenSight Biologics
Responsible party
Sponsor
First posted
Jan 12, 2016
Start date
Jan 2016
Primary completion
Jan 2018
Completion
Dec 2018
Results posted
Jan 23, 2020
Last update
Mar 2, 2026

Study contacts

Patrick Yu Wai Man, MDPhDFRCOpht
principal investigator · Moorfields Eye Hospital NHS Foundation Trust

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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