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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) (REVERSE)

Primary Purpose

Optic, Atrophy, Hereditary, Leber

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
GS010
Sham Intravitreal Injection
Sponsored by
GenSight Biologics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Optic, Atrophy, Hereditary, Leber focused on measuring 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

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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.
  5. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing.
  6. Signed written informed consent.

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 human immunodeficiency virus (HIV).
  4. 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).

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 hypersensitivity to GS010 or its constituents.
  2. Contraindication 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 autoimmune-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.

Sites / Locations

  • Doheny Eye Center, University of California, Los Angeles
  • Department of Ophthalmology, Emory University School of Medicine
  • Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University
  • Centre National Hospitalier d'Ophtalmologie des Quinze-Vingt
  • Department of Neurology, University of Munich, Friedrich-Baur-Institute
  • IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria
  • Moorfields Eye Hospital NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

GS010-treated Eyes

Sham-treated Eyes

Arm Description

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®.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).
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.
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.
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).
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).
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).
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).
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.
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.
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.
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.

Full Information

First Posted
January 7, 2016
Last Updated
January 17, 2020
Sponsor
GenSight Biologics
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1. Study Identification

Unique Protocol Identification Number
NCT02652780
Brief Title
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)
Acronym
REVERSE
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
January 2016 (Actual)
Primary Completion Date
January 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GenSight Biologics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GS010-treated Eyes
Arm Type
Experimental
Arm Description
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®.
Arm Title
Sham-treated Eyes
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
GS010
Other Intervention Name(s)
Lenadogene Nolparvovec, rAAV2/2-ND4
Intervention Description
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®.
Intervention Type
Device
Intervention Name(s)
Sham Intravitreal Injection
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48
Description
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 Outcome Measure Information:
Title
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96
Description
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
Title
Number of Eye Responders to Treatment at Week 48 and Week 96
Description
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
Title
Number of Subject Responders to Treatment at Week 48 and Week 96
Description
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
Title
Change From Baseline in GCL Macular Volume at Week 48 and Week 96
Description
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
Title
Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96
Description
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
Title
Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96
Description
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
Title
Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96
Description
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
Title
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96
Description
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
Title
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96
Description
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
Title
Change From Baseline in Contrast Sensitivity at Week 48 and Week 96
Description
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
Title
Change From Baseline in Color Vision
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
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. 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. Ability to obtain adequate pupillary dilation to permit thorough ocular examination and testing. Signed written informed consent. Inclusion Criteria: 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). 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. 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. 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. 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrick Yu Wai Man, MDPhDFRCOpht
Organizational Affiliation
Moorfields Eye Hospital NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Doheny Eye Center, University of California, Los Angeles
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Department of Ophthalmology, Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Neuro Ophthalmologic Associates, Wills Eye Hospital, Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Facility Name
Centre National Hospitalier d'Ophtalmologie des Quinze-Vingt
City
Paris
Country
France
Facility Name
Department of Neurology, University of Munich, Friedrich-Baur-Institute
City
Munich
ZIP/Postal Code
80336
Country
Germany
Facility Name
IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Clinica Neurologica, Ospedale Bellaria
City
Bologna
Country
Italy
Facility Name
Moorfields Eye Hospital NHS Foundation Trust
City
London
ZIP/Postal Code
EC1V 2PD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
34108929
Citation
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.
Results Reference
derived
Links:
URL
http://ghr.nlm.nih.gov/condition/leber-hereditary-optic-neuropathy
Description
National Library of Medicine's Genetics Home Reference for Leber Hereditary Optic Neuropathy
URL
https://www.nlm.nih.gov/medlineplus/genesandgenetherapy.html
Description
National Library of Medicine's Genes and Gene Therapy

Learn more about this trial

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)

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