Leber Hereditary Optic NeuropathyPhase 3REFLECTNCT03293524
Efficacy & Safety Study of Bilateral IVT Injection of GS010 in LHON Subjects Due to the ND4 Mutation for up to 1 Year
A Phase 3 study testing GS010 in people with Leber Hereditary Optic Neuropathy, run by GenSight Biologics at 13 sites in 7 countries.
Trial summary
The goal of this clinical trial is to assess the efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year. Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Leber Hereditary Optic Neuropathy
- 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
- 98 participants
- Where
- 13 sitesin 7 countries
- Study dates
- 12 Mar 2018to 23 Jul 2024
- 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
Main Selection Criteria:
- Age 15 years or older on the date of signed informed consent.
- Clinically manifested vision loss due to ND4 LHON, to any extent, in at least one eye.
- Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).
Main Non-Selection Criteria:
- Contraindication to intravitreal injection in any eye.
- Subjects refusing to discontinue idebenone.
- Previous vitrectomy in either eye.
- Narrow angle in any eye contra-indicating pupillary dilation.
- Presence of known/documented mutations, other than the G11778A ND4 LHON-causing mutation, which are known to cause pathology of the optic nerve, retina or afferent visual system.
- History of recurrent uveitis (idiopathic or immune-related) or active ocular inflammation.
Main Inclusion Criteria:
- Vision loss duration of ≤ 365 days (i.e. ≤ 1 year) in each affected eye at Inclusion Visit (Visit 2).
- Each eye of the subject must maintain at least Hand Motion (HM) visual acuity, as defined by the study's SOP for visual acuity testing.
- 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 subject's mitochondrial DNA.
Main Exclusion Criteria:
- Light Perception (LP) or No Light Perception (NLP) visual acuity in any eye, as defined by the study's standard operating procedure (SOP) for visual acuity testing.
- Presence of active infectious conjunctivitis, keratitis, scleritis or endophthalmitis in either eye.
- Presence of alcoholism, alcohol dependence, or alcohol or drug abuse (excluding nicotine).
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
United States7 sites
Emory Healthcare - The Emory Clinic
Atlanta, Georgia, 30322
University of Colorado Health Eye Center
Aurora, Colorado, 80045
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Vanderbilt Eye Institute
Nashville, Tennessee, 37232
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Doheny Eye Center UCLA Pasadena
Pasadena, California, 91105
Departments of Neurology and Ophthalmology, Wills Eye Hospital and Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Italy1 site
IRCCS Istituto delle Scienze Neurologiche di Bologna (ISNB) Clinica Neurologica
Bologna, 40139
United Kingdom1 site
Moorfields Eye Hospital
London, Greater London, EC1V 2PD
About this study
Official title: Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year
The goal of this clinical trial is to assess the efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year.
Read the detailed description
The REFLECT study is a Phase 3, international, multi-center, randomized, double-masked, placebo-controlled, clinical trial. The primary objective is to assess the efficacy of intravitreal (IVT) of GS010 compared to IVT of placebo in second-affected/not-yet-affected eyes at 1.5 years post-treatment, by analyzing the change from baseline of the visual acuity in ND4 LHON subjects with vision loss up to one year.
- Conditions
- Leber Hereditary Optic Neuropathy
- Being tested
- GS010, Placebo
- Keywords
- Leber Hereditary Optic Atrophy, Leber Hereditary Optic Neuropathy, LHON, Eye Diseases, Hereditary Eye Diseases, Inherited retinal dystrophies or degeneration, Gene Therapy, Intravitreal Injections, Mitochondrial Disease, AAV2 Vectors, Hereditary Optic Atrophy
- Medical subject headings
- Optic Atrophy, Hereditary, Leber, Eye Diseases, Eye Diseases, Hereditary, Mitochondrial Diseases, Optic Atrophies, Hereditary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS010Genetic
Also called Lenadogene nolparvovec
GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 was administrated via intravitreal injection containing 1.2/1.3E11 vg in 90 μL balanced sterile saline solution (BSSS).
PlaceboDrug
The placebo is a balanced sterile saline solution (BSSS) used for IVT. The placebo was administered via intravitreal injection in a volume of 90 μL.
| Study group | Role | What they receive |
|---|---|---|
| GS010-GS010 | Experimental | Patients received single IVT injection of GS010 in both their first-affected eye and their second-affected/not-yet-affected eye at a droplet digital polymerase chain reaction (ddPCR) dose of 1.2/1.3E11 vg in 90 μL for each eye.
Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0). Receives: Genetic: GS010 |
| GS010-Placebo | Placebo comparator | Patients received single IVT injection of GS010 in their first-affected eye and placebo IVT injection in their second-affected/not-yet-affected eye.
Patients received IVT lenadogene nolparvovec in their first-affected eye (ddPCR dose of 1.2/1.3E11 vg in a volume of 90 μL) and placebo IVT injection (volume of 90 μL) in their second-affected/not-yet-affected eye.
Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0). Receives: Genetic: GS010; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
The primary efficacy endpoint was the change from baseline of BCVA reported with LogMAR at 1.5-year post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.
Measured: at 1.5 years post-treatment, in the second-affected/not-yet affected eyes
Secondary outcomes (6)
Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
Change from baseline of BCVA reported with LogMAR at 5 years post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.
Measured: at 5 years post-treatment, in the second-affected/not-yet affected eyes
Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment
Proportion of patients with both eyes off-chart, defined as those patients unable to read letter on the ETDRS chart, who had at least one eye on-chart, defined as those patients able to read letters on the ETDRS chart (at either 4 meters or 1 meter) at 5 years
Measured: From baseline to 5 years post-treatment
Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years
Proportion of patients with an improvement of at least -0.3 LogMAR (≥ +15 ETDRS letters) from nadir to year 5 in at least one eye. Nadir was defined for each eye of each subject as the worst value observed from baseline to year 5
Measured: From nadir to 5 years post-treatment
Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years
Proportion of patients with clinically relevant recovery (CRR) from nadir that was defined as patient with a CRR in at least one eye - Patient with at least one eye which was on chart at nadir, and which had an improvement of at least -0.2 LogMAR from nadir, or which was off-chart at nadir but became on-chart
Measured: From nadir to 5 years post-treatment
Responder Analyses- Clinically Relevant Benefit at 5 Years
Proportion of patients who had clinically relevant stabilization (CRS), defined as eyes with LogMAR BCVA < 1 at baseline and at 5 years post-treatment or had a clinically relevant recovery (CRR) from nadir. The best response observed in either eye was considered.
Measured: From baseline nadir to 5 years post-treatment
Quality of Life Questionnaire: VFQ-25 - Composite Score
Change from baseline to 5 years follow up in the Visual Function Questionnaire (VFQ-25) composite score. The VFQ-25 is a patient-reported outcome instrument assessing vision-related quality of life and consists of a base set of 25 vision-targeted questions representing 11 vision-related constructs plus an additional single-item general health rating question. Each item was converted to a 0-100 scale for scoring, where 100 represents the best possible score on the measure and 0 represents the worst. Items within each subscale were averaged to create 12 subscale scores (11 subscales related to vision + 1 subscale related to general health). The vision-related subscale scores (excluding the general health rating question) were then averaged to calculate the composite score.
Measured: From baseline to 5 years post-treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2017
- Study start12 Mar 2018
- Primary completion23 Jul 2024
- Study completion23 Jul 2024
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 (1)Papers the sponsor has linked to this study.
- Other trials for Leber Hereditary Optic NeuropathyStudies 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
- Model description
- Each participant had an eye designated as first-affected eye, and a fellow eye designated as either second-affected eye or not-yet-affected eye at the Screening Visit based on non-equal vision loss duration. In participants reporting simultaneous onset of vision loss in both eyes, the second-affected eye was randomly selected between both eyes. All participants received GS010 in their first-affected eye and were randomized in a 1:1 ratio to receive either GS010 (GS010- GS010 treatment arm) or placebo (GS010-Placebo treatment arm) in the second-affected/not-yet-affected eye.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 98 participants (actual)
Sponsor and investigators
- Lead sponsor
- GenSight Biologics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nancy Newman, MD, Principal investigator, Emory University Hospital Atlanta, Georgia, United States, 30322Patrick Yu-Wai-Man, PhD, Principal investigator, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03293524
- Sponsor's protocol ID
- GS-LHON-CLIN-05
- Other IDs
- 2017-002187-40, 2017
- Acronym
- REFLECT
- Status last verified
- Mar 2026
- First submitted
- 19 Sep 2017
- Last updated
- 16 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
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
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Bilateral Intravitreal Injection of GS010: A Randomized, Double-Masked, Placebo-Controlled Trial in Subjects Affected With G11778A ND4 Leber Hereditary Optic Neuropathy for Up to One Year
- ClinicalTrials.gov ID
- NCT03293524
- Acronym / sponsor ID
- REFLECT / GS-LHON-CLIN-05
- Conditions
- Leber Hereditary Optic Neuropathy
- Keywords
- Leber Hereditary Optic Atrophy, Leber Hereditary Optic Neuropathy, LHON, Eye Diseases, Hereditary Eye Diseases, Inherited retinal dystrophies or degeneration, Gene Therapy, Intravitreal Injections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 98 participants (actual)
- Lead sponsor
- GenSight BiologicsIndustry (pharma, biotech, devices)
- Study start
- 12 Mar 2018 (actual)
- Primary completion
- 23 Jul 2024 (actual)
- Study completion
- 23 Jul 2024 (actual)
- First posted
- 26 Sep 2017 (actual)
- Results
- Posted 16 Apr 2026
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 efficacy and safety of GS010 gene therapy - (lenadogene nolparvovec) in subjects with LHON due to the G11778A ND4 mitochondrial mutation with a vision loss up to one year.
Detailed description
The REFLECT study is a Phase 3, international, multi-center, randomized, double-masked, placebo-controlled, clinical trial. The primary objective is to assess the efficacy of intravitreal (IVT) of GS010 compared to IVT of placebo in second-affected/not-yet-affected eyes at 1.5 years post-treatment, by analyzing the change from baseline of the visual acuity in ND4 LHON subjects with vision loss up to one year.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Each participant had an eye designated as first-affected eye, and a fellow eye designated as either second-affected eye or not-yet-affected eye at the Screening Visit based on non-equal vision loss duration. In participants reporting simultaneous onset of vision loss in both eyes, the second-affected eye was randomly selected between both eyes. All participants received GS010 in their first-affected eye and were randomized in a 1:1 ratio to receive either GS010 (GS010- GS010 treatment arm) or placebo (GS010-Placebo treatment arm) in the second-affected/not-yet-affected eye.
| Arm | Type | Receives |
|---|---|---|
| GS010-GS010 | Experimental | Genetic: GS010Patients received single IVT injection of GS010 in both their first-affected eye and their second-affected/not-yet-affected eye at a droplet digital polymerase chain reaction (ddPCR) dose of 1.2/1.3E11 vg in 90 μL for each eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0). |
| GS010-Placebo | Placebo comparator | Genetic: GS010, Drug: PlaceboPatients received single IVT injection of GS010 in their first-affected eye and placebo IVT injection in their second-affected/not-yet-affected eye. Patients received IVT lenadogene nolparvovec in their first-affected eye (ddPCR dose of 1.2/1.3E11 vg in a volume of 90 μL) and placebo IVT injection (volume of 90 μL) in their second-affected/not-yet-affected eye. Treatment could be performed either on a single day (1 IVT injection in each eye on Day 0) or on 2 consecutive days (1st IVT injection on Day -1 and 2nd IVT injection on Day 0). |
Who may qualify
- Ages
- 15 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
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 nolparvovecGS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). GS010 was administrated via intravitreal injection containing 1.2/1.3E11 vg in 90 μL balanced sterile saline solution (BSSS). | Genetic | GS010-GS010, GS010-Placebo |
| PlaceboThe placebo is a balanced sterile saline solution (BSSS) used for IVT. The placebo was administered via intravitreal injection in a volume of 90 μL. | Drug | GS010-Placebo |
Primary outcome
Change From Baseline of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
Time frame: at 1.5 years post-treatment, in the second-affected/not-yet affected eyes
The primary efficacy endpoint was the change from baseline of BCVA reported with LogMAR at 1.5-year post-treatment, in the second-affected/not-yet-affected eyes of ND4 LHON patients with vision loss up to one year. LogMAR BCVA was used to represent BCVA.
6 secondary outcomes
Change From Baseline of the BCVA Reported With LogMAR at 5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes
Time frame: at 5 years post-treatment, in the second-affected/not-yet affected eyes
Proportion of Patients Who Switched From Off-chart Eyes to On-chart Eyes at 5 Years Post-treatment
Time frame: From baseline to 5 years post-treatment
Responder Analyses - Improvements From Nadir (Gainer Eyes) at 5 Years
Time frame: From nadir to 5 years post-treatment
Responder Analyses - Clinically Relevant Recovery From Nadir at 5 Years
Time frame: From nadir to 5 years post-treatment
Responder Analyses- Clinically Relevant Benefit at 5 Years
Time frame: From baseline nadir to 5 years post-treatment
Quality of Life Questionnaire: VFQ-25 - Composite Score
Time frame: From baseline to 5 years post-treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 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.
- GenSight Biologics websiteLink provided by the sponsor.
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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.
Nancy Newman, MD principal investigator
Emory University Hospital Atlanta, Georgia, United States, 30322
Patrick Yu-Wai-Man, PhD principal investigator
John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, CB2 0PY, United Kingdom
13 sites in 7 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 Leber Hereditary Optic Neuropathy, run by GenSight Biologics at 13 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Belgium, France, Italy, Spain and 2 more countries. 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 16 Apr 2026). 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 of the Best Corrected Visual Acuity (BCVA) Reported With Log of the Minimal Angle of Resolution (LogMAR) at 1.5 Years Post-treatment, in the Second Affected/Not-yet Affected Eyes (time frame: at 1.5 years post-treatment, in the second-affected/not-yet affected eyes). 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 NCT03293524, which also lists 1 linked publication.
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 16 Apr 2026.