Trial Outcomes & Findings for Efficacy Study of GS010 for the Treatment of Vision Loss up to 6 Months From Onset in LHON Due to the ND4 Mutation (NCT NCT02652767)

Last Updated: 2022-07-29

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

39 participants

Primary outcome timeframe

Baseline and Week 48

Results posted on

2022-07-29

Participant Flow

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	39
Overall Study Completed Week 48	38
Overall Study COMPLETED	35
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Death	2
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=39 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.
Age, Continuous	36.3 years STANDARD_DEVIATION 15.5 • n=39 Participants
Sex: Female, Male Female	7 Participants n=39 Participants
Sex: Female, Male Male	32 Participants n=39 Participants
Weight	73.9 kilograms STANDARD_DEVIATION 17.8 • n=39 Participants
Height	174.5 centimeters STANDARD_DEVIATION 7.7 • n=39 Participants

PRIMARY outcome

Timeframe: Baseline and Week 48

Population: 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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 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.	Sham-treated Eyes n=38 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.
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48	0.380 LogMAR Standard Error 0.129	0.392 LogMAR Standard Error 0.129

SECONDARY outcome

Timeframe: Baseline; Week 72 and Week 96

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 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.	Sham-treated Eyes n=38 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.
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) Week 72	0.192 LogMAR Standard Error 0.104	0.216 LogMAR Standard Error 0.104
Change From Baseline in ETDRS Visual Acuity (Quantitative Score) Week 96	0.178 LogMAR Standard Error 0.120	0.207 LogMAR Standard Error 0.120

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 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.	Sham-treated Eyes n=38 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.
Number of Eye Responders to Treatment Week 48 Definition 1	4 Eyes	3 Eyes
Number of Eye Responders to Treatment Week 48 Definition 2	9 Eyes	10 Eyes
Number of Eye Responders to Treatment Week 72 Definition 1	6 Eyes	5 Eyes
Number of Eye Responders to Treatment Week 72 Definition 2	11 Eyes	9 Eyes
Number of Eye Responders to Treatment Week 96 Definition 1	7 Eyes	5 Eyes
Number of Eye Responders to Treatment Week 96 Definition 2	13 Eyes	11 Eyes

SECONDARY outcome

Timeframe: Week 48; Week 72 and Week 96

Population: 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.

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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 Participants 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.	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.
Number of Subject Responders to Treatment Week 48	4 Participants	—
Number of Subject Responders to Treatment Week 72	2 Participants	—
Number of Subject Responders to Treatment Week 96	5 Participants	—

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 and Week 96

Population: 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.

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).

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=36 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.	Sham-treated Eyes n=37 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.
Change From Baseline in GCL Macular Volume Week 48	-0.184 mm^3 Standard Error 0.014	-0.207 mm^3 Standard Error 0.014
Change From Baseline in GCL Macular Volume Week 72	-0.204 mm^3 Standard Error 0.015	-0.226 mm^3 Standard Error 0.015
Change From Baseline in GCL Macular Volume Week 96	-0.208 mm^3 Standard Error 0.015	-0.221 mm^3 Standard Error 0.015

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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).

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=37 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.	Sham-treated Eyes n=37 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.
Change From Baseline in RNFL Temporal Quadrant Thickness Week 48	-22.8 µm Standard Error 1.0	-24.7 µm Standard Error 1.0
Change From Baseline in RNFL Temporal Quadrant Thickness Week 72	-25.5 µm Standard Error 0.9	-26.0 µm Standard Error 0.9
Change From Baseline in RNFL Temporal Quadrant Thickness Week 96	-24.2 µm Standard Error 0.8	-26.1 µm Standard Error 0.8

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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).

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=37 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.	Sham-treated Eyes n=37 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.
Change From Baseline in RNFL Papillomacular Bundle Thickness Week 48	-10.4 µm Standard Error 1.0	-12.4 µm Standard Error 1.0
Change From Baseline in RNFL Papillomacular Bundle Thickness Week 72	-12.8 µm Standard Error 1.0	-13.1 µm Standard Error 1.0
Change From Baseline in RNFL Papillomacular Bundle Thickness Week 96	-11.2 µm Standard Error 1.0	-13.3 µm Standard Error 1.0

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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).

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=36 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.	Sham-treated Eyes n=37 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.
Change From Baseline in ETDRS Total Macular Volume Week 48	-0.578 mm^3 Standard Error 0.041	-0.708 mm^3 Standard Error 0.040
Change From Baseline in ETDRS Total Macular Volume Week 72	-0.686 mm^3 Standard Error 0.048	-0.782 mm^3 Standard Error 0.048
Change From Baseline in ETDRS Total Macular Volume Week 96	-0.720 mm^3 Standard Error 0.050	-0.800 mm^3 Standard Error 0.050

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=11 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.	Sham-treated Eyes n=8 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.
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II Week 48	3.5 decibels (dB) Standard Deviation 12.3	-7.4 decibels (dB) Standard Deviation 12.8
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II Week 72	6.3 decibels (dB) Standard Deviation 7.8	-5.1 decibels (dB) Standard Deviation 11.9
Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II Week 96	3.3 decibels (dB) Standard Deviation 12.7	1.4 decibels (dB) Standard Deviation 19.5

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 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.	Sham-treated Eyes n=38 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.
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II Baseline MD	-16.26 decibels (dB) Standard Deviation 10.59	-16.73 decibels (dB) Standard Deviation 11.48
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II Week 48 MD	-24.26 decibels (dB) Standard Deviation 9.37	-23.76 decibels (dB) Standard Deviation 10.40
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II Week 72 MD	-23.33 decibels (dB) Standard Deviation 9.41	-22.94 decibels (dB) Standard Deviation 10.11
Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II Week 96 MD	-23.31 decibels (dB) Standard Deviation 9.41	-22.70 decibels (dB) Standard Deviation 9.88

SECONDARY outcome

Timeframe: Baseline; Week 48; Week 72 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 negative change from baseline indicates worsening in symptoms.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=38 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.	Sham-treated Eyes n=38 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.
Change From Baseline in Contrast Sensitivity Week 48	-0.35 LogCS Standard Error 0.07	-0.33 LogCS Standard Error 0.07
Change From Baseline in Contrast Sensitivity Week 72	-0.25 LogCS Standard Error 0.07	-0.28 LogCS Standard Error 0.07
Change From Baseline in Contrast Sensitivity Week 96	-0.27 LogCS Standard Error 0.07	-0.25 LogCS Standard Error 0.07

SECONDARY outcome

Timeframe: Baseline; Week 48 and Week 96

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.

Outcome measures

Outcome measures
Measure	GS010-treated Eyes n=21 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.	Sham-treated Eyes n=21 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.
Change From Baseline in Color Vision Week 48	133.1 score on a scale Standard Deviation 290.7	235.6 score on a scale Standard Deviation 392.3
Change From Baseline in Color Vision Week 96	97.7 score on a scale Standard Deviation 342.2	213.5 score on a scale Standard Deviation 393.1

Adverse Events

All Participants

Serious events: 3 serious events

Other events: 38 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=39 participants at risk 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.
Hepatobiliary disorders Alcoholic liver disease	2.6% 1/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Injury, poisoning and procedural complications Alcohol poisoning	2.6% 1/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Metabolism and nutrition disorders Malnutrition	2.6% 1/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Psychiatric disorders Alcohol withdrawal syndrome	2.6% 1/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Renal and urinary disorders Renal failure	2.6% 1/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.

Other adverse events

Other adverse events
Measure	All Participants n=39 participants at risk 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.
Infections and infestations Nasopharyngitis	17.9% 7/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Infections and infestations Ear infection	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Nervous system disorders Headache	15.4% 6/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Nervous system disorders Migraine	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations Gamma-glutamyltransferase increased	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations Alanine aminotransferase increased	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations Blood glucose increased	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations Neutrophil count increased	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations White blood cell count increased	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Psychiatric disorders Anxiety	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Psychiatric disorders Depression	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Vascular disorders Hypertension	15.4% 6/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Social circumstances Alcohol use	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Anterior chamber cell	15.4% 6/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Anterior chamber flare	12.8% 5/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Anterior chamber inflammation	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Autoimmune uveitis	38.5% 15/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Chalazion	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Conjunctival haemorrhage	17.9% 7/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Conjunctival hyperaemia	12.8% 5/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Corneal disorder	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Eye irritation	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Eye pain	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Foreign body sensation in eyes	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Iridocyclitis	46.2% 18/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Iris atrophy	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Iris transillumination defect	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Keratic precipitates	23.1% 9/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Macular oedema	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Photopsia	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Punctate keratitis	46.2% 18/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Vitreal cells	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Vitreous disorder	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Vitreous floaters	7.7% 3/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Eye disorders Vitritis	17.9% 7/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Infections and infestations Conjunctivitis	5.1% 2/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.
Investigations Intraocular pressure increased	33.3% 13/39 • From first dose to end of study (a maximum of 96 weeks) Safety population: All participants who were randomized and received study treatments. Because all participants received both study treatment and the sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular events. Reported events include AEs associated with both GS010 and the sham procedure.

Additional Information

Magali Taiel CMO

GenSight Biologics

Phone: 1 76 21 72 26

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place