Efficacy Study of GS010 for the Treatment of Vision Loss... | NCT02652767

ID	Type	Description	Link
2015-001265-11	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GS010-treated Eyes	Experimental	Each participant will have one eye randomly selected to receive a single injection of GS010 and the other eye will receive a sham injection. GS010-treated Eyes: GS010 is a recombinant adeno-associated viral vector serotype 2 (rAAV2/2) containing the wild-type ND4 gene (rAAV2/2-ND4). Participants will receive a single dose of GS010 in one of their randomly selected eyes, via intravitreal injection containing 9E10 viral genomes in 90μL balanced salt solution (BSS) plus 0.001% Pluronic F68®.	Biological: GS010
Sham-treated Eyes	Sham Comparator	Each participant will have one eye randomly selected to receive GS010 and the other eye will receive a sham injection. Eyes receiving sham injection will undergo the same preparatory procedures as eyes receiving GS010 injection, including pupillary dilation, topical anti-infection and topical anesthetic procedures. Sham intravitreal injection will be performed by applying pressure to the eye at the location of a typical intravitreal injection procedure using the blunt end of a syringe without a needle.	Device: Sham Intravitreal Injection

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GS010	Biological	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®.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 48 score - Baseline score).	Baseline and Week 48

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in ETDRS Visual Acuity (Quantitative Score)	Visual acuity was derived from the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms. Change = (Week 72 score - Baseline score) or (Week 96 score - Baseline score). Missing data was imputed by the linear interpolation method.

Eligibility Module

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 participant testimony, in at least one eye for ≤180 days in duration and if both eyes are affected the duration of vision loss in both eyes must be ≤180 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 intravitreal (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 Leber Hereditary Optical Neuropathy (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.
Have a negative pregnancy test for women of childbearing potential (a woman who is 2 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 intra-ocular pressure (IOP) greater than 25 mmHg, despite maximal medical therapy with IOP-lowering agents.
Active ocular inflammation or history of idiopathic or autoimmune-associated uveitis.
Participants participating in another clinical trial and receiving an investigational medicinal product 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.

Name	Affiliation	Role
Nancy J. Newman, MD	Department of Ophthalmology, Emory University School of Medicine	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Doheny Eye Center, University of California, Los Angeles		Los Angeles	California	91105	United States

PubMed Identifier	Type	Citation	Retractions
36449262	Derived	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.
34108929

Label	URL
National Library of Medicine's Genetics Home Reference for Leber Hereditary Optic Neuropathy	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	All Participants	All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to receive GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Nov 7, 2016	Jan 17, 2020

ID	Title	Description
BG000	All Participants	All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to receive GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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. Visual acuity is measured in "logarithm of the minimal angle of resolution" (LogMAR), which 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. A positive change from baseline indicates a worsening in symptoms.

Change = (Week 48 score - Baseline score).

Intent-to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.

Posted

Least Squares Mean

Standard Error

LogMAR

Baseline and Week 48

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Units	Counts
Participants	OG00038 OG00138
Eyes	OG00038 OG001

Title

Denominators

Categories

Title	Measurements
	OG0000.380± 0.129 OG0010.392± 0.129

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed model of analysis of covariance (ANCOVA) was used with change from baseline at Week 48 as the response, and participants, eyes of the participant as random factor, treatment and baseline LogMAR value as covariates in the model. P-value is used to assess the significance of the difference between All-GS010 and All-Sham with respect to change of LogMAR from baseline.	ANCOVA		0.8890		Mean Difference (Net)	-0.012			2-Sided	95	-0.182	0.158					Superiority

Secondary

Change From Baseline in ETDRS Visual Acuity (Quantitative Score)

1 ETDRS line = 5 letters

1 ETDRS line = 0.1 LogMAR

A lower LogMAR score denotes better visual acuity. A positive change from baseline indicates a worsening in symptoms.

Change = (Week 72 score - Baseline score) or (Week 96 score - Baseline score). Missing data was imputed by the linear interpolation method.

Posted

Least Squares Mean

Standard Error

LogMAR

Baseline; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.

Secondary

Number of Eye Responders to Treatment

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.

Posted

Count of Units

Eyes

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes

Secondary

Number of Subject Responders to Treatment

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.

For the Week 96 analysis, if no score was available for Week 96, the score from the previous visit was used.

Intent-to-treat (ITT) population: All participants that received study treatments, with data at the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.

Posted

Count of Participants

Participants

Week 48; Week 72 and Week 96

ID	Title	Description
OG000	All Participants	All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to receive GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.

Secondary

Change From Baseline in GCL Macular Volume

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).

Intent -to-treat (ITT) population: All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit. 1 participant was excluded from the ITT population due to receiving a smaller volume of study treatment than specified in the protocol. Participants received GS010 and Sham simultaneously.

Posted

Least Squares Mean

Standard Error

mm^3

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Secondary

Change From Baseline in RNFL Temporal Quadrant Thickness

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).

Posted

Least Squares Mean

Standard Error

µm

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Secondary

Change From Baseline in RNFL Papillomacular Bundle Thickness

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).

Posted

Least Squares Mean

Standard Error

µm

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Secondary

Change From Baseline in ETDRS Total Macular Volume

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).

Posted

Least Squares Mean

Standard Error

mm^3

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Secondary

Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II

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.

Posted

Mean

Standard Deviation

decibels (dB)

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001

Secondary

Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II

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.

Posted

Mean

Standard Deviation

decibels (dB)

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.
OG001	Sham-treated Eyes	All eyes that received the Sham. Each participant was randomly assigned GS010 in either the right or left eye, the eye not assigned GS010 received the sham procedure. The eye assigned to the Sham received one single sham intravitreal (IVT) injection, which was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle. The same participants also received GS010 in the right or left eye, which did not receive the sham procedure, at the same study visit.

Secondary

Change From Baseline in Contrast Sensitivity

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 negative change from baseline indicates worsening in symptoms.

Posted

Least Squares Mean

Standard Error

LogCS

Baseline; Week 48; Week 72 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.

Secondary

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 positive change from baseline indicates a worsening in symptoms.

Posted

Mean

Standard Deviation

score on a scale

Baseline; Week 48 and Week 96

Eyes

ID	Title	Description
OG000	GS010-treated Eyes	All eyes that received the study treatment, GS010. Each participant was randomly assigned GS010 in either the right or left eye. The eye assigned to GS010 received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 μL. The injection was performed in the vitreous humor under local anesthesia. The same participants also received the sham procedure in the right or left eye, which was not assigned to receive GS010, at the same study visit.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	All Participants	All participants who were enrolled and received both study treatments, GS010 and Sham. All participants in the study received both GS010 and the sham procedure simultaneously. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham procedure in the eye not assigned to receive GS010, at the same study visit. GS010: Either the right or left eye received one single dose of GS010 (9E10 vg/eye) via an intravitreal (IVT) injection. The volume of the injected formula was 90 µL. The injection was performed in the vitreous humor under local anesthesia. Sham: Either the right or left eye (the eye not randomly assigned to GS010) received the sham procedure. One single sham IVT injection was performed by applying pressure to the eye at the location of a typical IVT injection procedure, using the blunt end of a syringe without a needle.	2	39	3	39	38	39

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0007 affected39 at risk
Ear infection	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment		EG0006 affected39 at risk
Migraine	Nervous system disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Blood glucose increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Neutrophil count increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
White blood cell count increased	Investigations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Depression	Psychiatric disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment		EG0006 affected39 at risk
Alcohol use	Social circumstances	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Anterior chamber cell	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0006 affected39 at risk
Anterior chamber flare	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0005 affected39 at risk
Anterior chamber inflammation	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Autoimmune uveitis	Eye disorders	MedDRA 20.1	Systematic Assessment	The verbatim term for all events of "autoimmune uveitis" is "intermediate uveitis".	EG00015 affected39 at risk
Chalazion	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Conjunctival haemorrhage	Eye disorders	MedDRA 20.1	Systematic Assessment	1/7 affected participants experienced this event in the sham-treated eyes.	EG0007 affected39 at risk
Conjunctival hyperaemia	Eye disorders	MedDRA 20.1	Systematic Assessment	4/5 affected participants experienced this event in the sham-treated eyes.	EG0005 affected39 at risk
Corneal disorder	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Eye irritation	Eye disorders	MedDRA 20.1	Systematic Assessment	1/2 affected participants experienced this event in the sham-treated eyes.	EG0002 affected39 at risk
Eye pain	Eye disorders	MedDRA 20.1	Systematic Assessment	1/3 affected participants experienced this event in the sham treated eyes.	EG0003 affected39 at risk
Foreign body sensation in eyes	Eye disorders	MedDRA 20.1	Systematic Assessment	1/2 affected participants experienced this event in the sham treated eyes.	EG0002 affected39 at risk
Iridocyclitis	Eye disorders	MedDRA 20.1	Systematic Assessment	2/18 affected participants experienced this event in the sham-treated eyes.	EG00018 affected39 at risk
Iris atrophy	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Iris transillumination defect	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Keratic precipitates	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0009 affected39 at risk
Macular oedema	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Photopsia	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Punctate keratitis	Eye disorders	MedDRA 20.1	Systematic Assessment	3/18 affected participants experienced this event in the sham-treated eyes.	EG00018 affected39 at risk
Vitreal cells	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Vitreous disorder	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Vitreous floaters	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0003 affected39 at risk
Vitritis	Eye disorders	MedDRA 20.1	Systematic Assessment		EG0007 affected39 at risk
Conjunctivitis	Infections and infestations	MedDRA 20.1	Systematic Assessment		EG0002 affected39 at risk
Intraocular pressure increased	Investigations	MedDRA 20.1	Systematic Assessment	1/13 affected participants experienced this event in the sham-treated eyes.	EG00013 affected39 at risk

ID	Term
D029242	Optic Atrophy, Hereditary, Leber
D005128	Eye Diseases
D015785	Eye Diseases, Hereditary
D030342	Genetic Diseases, Inborn
D028361	Mitochondrial Diseases
D009422	Nervous System Diseases
D019636	Neurodegenerative Diseases

ID	Term
D015418	Optic Atrophies, Hereditary
D009896	Optic Atrophy
D009901	Optic Nerve Diseases
D003389	Cranial Nerve Diseases
D020271	Heredodegenerative Disorders, Nervous System
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Alcoholic liver disease	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected39 at risk
Alcohol poisoning	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected39 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected39 at risk
Alcohol withdrawal syndrome	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected39 at risk
Renal failure	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected39 at risk