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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02652780
Recruitment Status : Completed
First Posted : January 12, 2016
Results First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Information provided by (Responsible Party):
GenSight Biologics

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Optic, Atrophy, Hereditary, Leber
Interventions Biological: GS010
Device: Sham Intravitreal Injection
Enrollment 37
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Participants
Hide Arm/Group Description

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 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 procedure: 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.

Period Title: Overall Study
Started 37
Completed 37
Not Completed 0
Arm/Group Title All Participants
Hide Arm/Group Description

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 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 procedure: 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 Number of Baseline Participants 37
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
<=18 years
4
  10.8%
Between 18 and 65 years
32
  86.5%
>=65 years
1
   2.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 37 participants
34.2  (15.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 37 participants
Female
8
  21.6%
Male
29
  78.4%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 37 participants
20
  54.1%
United Kingdom Number Analyzed 37 participants
2
   5.4%
France Number Analyzed 37 participants
5
  13.5%
Germany Number Analyzed 37 participants
6
  16.2%
Italy Number Analyzed 37 participants
4
  10.8%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 37 participants
80.1  (21.0)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimetres
Number Analyzed 37 participants
174.4  (7.8)
1.Primary Outcome
Title Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 48
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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, at the same study visit.

Overall Number of Participants Analyzed 37 37
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 37
Least Squares Mean (Standard Error)
Unit of Measure: LogMAR
-0.219  (0.055) -0.211  (0.055)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection GS010-treated Eyes, Sham-treated Eyes
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8783
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.008
Confidence Interval (2-Sided) 95%
-0.119 to 0.102
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in ETDRS Visual Acuity (Quantitative Score) at Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 37
Least Squares Mean (Standard Error)
Unit of Measure: LogMAR
-0.308  (0.068) -0.259  (0.068)
3.Secondary Outcome
Title Number of Eye Responders to Treatment at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 37
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 37
Count of Units
Unit of Measure: Eyes
Definition 1: Week 48
7
  18.9%
5
  13.5%
Definition 1: Week 96
12
  32.4%
6
  16.2%
Definition 2: Week 48
10
  27.0%
13
  35.1%
Definition 2: Week 96
17
  45.9%
19
  51.4%
4.Secondary Outcome
Title Number of Subject Responders to Treatment at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants that received study treatments, with data at the applicable post dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title All Participants
Hide Arm/Group Description:

All participants who were enrolled and received both study treatments, GS010 and Sham. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham comparator in the eye not assigned to GS010 at the same 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 procedure: 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 Number of Participants Analyzed 37
Measure Type: Count of Participants
Unit of Measure: Participants
Week 48
37
 100.0%
Week 96
37
 100.0%
5.Secondary Outcome
Title Change From Baseline in GCL Macular Volume at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 36 36
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
36 36
Least Squares Mean (Standard Error)
Unit of Measure: mm^3
Week 48 -0.003  (0.012) -0.038  (0.012)
Week 96 -0.018  (0.012) -0.031  (0.012)
6.Secondary Outcome
Title Change From Baseline in RNFL Temporal Quadrant Thickness at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 36
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 36
Least Squares Mean (Standard Error)
Unit of Measure: µm
Week 48 Number Analyzed 37 Eyes 35 Eyes [1] 
-0.562  (0.988) -3.354  (1.017)
Week 96 Number Analyzed 35 Eyes [1]  36 Eyes
-1.791  (0.974) -2.042  (0.951)
[1]
35 participants
7.Secondary Outcome
Title Change From Baseline in Papillomacular Bundle Thickness at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 36
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 36
Least Squares Mean (Standard Error)
Unit of Measure: µm
Week 48 Number Analyzed 37 Eyes 35 Eyes [1] 
1.6  (1.3) -1.0  (1.4)
Week 96 Number Analyzed 35 Eyes [1]  36 Eyes
1.2  (1.3) 0.7  (1.3)
[1]
35 participants
8.Secondary Outcome
Title Change From Baseline in ETDRS Total Macular Volume at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 36 36
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
36 36
Least Squares Mean (Standard Error)
Unit of Measure: mm^3
Week 48 -0.104  (0.046) -0.224  (0.046)
Week 96 -0.200  (0.037) -0.265  (0.037)
9.Secondary Outcome
Title Change From Baseline in the Foveal Threshold Sensitivities Obtained With HVF Analyzer II at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 9 11
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
9 11
Mean (Standard Deviation)
Unit of Measure: decibels (dB)
Week 48 Number Analyzed 9 Eyes 11 Eyes
0.7  (8.9) -0.5  (11.9)
Week 96 Number Analyzed 8 Eyes [1]  9 Eyes [2] 
1.3  (8.0) 2.4  (10.8)
[1]
8 participants
[2]
9 participants
10.Secondary Outcome
Title Visual Field Mean Deviation in Decibels of Sensitivity Obtained With HVF Analyzer II at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 37
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 37
Mean (Standard Deviation)
Unit of Measure: decibels (dB)
Baseline MD -25.99  (8.37) -24.94  (9.70)
Week 48 MD -22.83  (9.43) -22.94  (9.80)
Week 96 MD -23.22  (8.98) -22.43  (9.39)
11.Secondary Outcome
Title Change From Baseline in Contrast Sensitivity at Week 48 and Week 96
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 37 37
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
37 37
Least Squares Mean (Standard Error)
Unit of Measure: LogCS
Week 48 0.19  (0.05) 0.09  (0.05)
Week 96 0.22  (0.06) 0.12  (0.06)
12.Secondary Outcome
Title Change From Baseline in Color Vision
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All participants and all eyes that received study treatments, with data at both Baseline and the applicable post-dose visit (Week 48 or Week 96). All participants received both GS010 and Sham simultaneously.
Arm/Group Title GS010-treated Eyes Sham-treated Eyes
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 24 25
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
24 25
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 48 Number Analyzed 24 Eyes 25 Eyes
-30.0  (255.0) -44.3  (182.2)
Week 96 Number Analyzed 23 Eyes [1]  24 Eyes [2] 
-10.3  (247.3) -61.0  (188.9)
[1]
23 participants
[2]
24 participants
Time Frame From first dose to end of study (a maximum of 96 weeks)
Adverse Event Reporting Description Because participants received both treatment and sham procedure simultaneously, adverse events (AEs) are reported overall for systemic and ocular AEs. Reported events include AEs associated with sham procedure.
 
Arm/Group Title All Participants
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All participants who were enrolled and received both study treatments, GS010 and Sham. Participants were randomly assigned to receive GS010 in either the right or left eye. The same participants also received the sham comparator in the eye not assigned to GS010 at the same 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 procedure: 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.

All-Cause Mortality
All Participants
Affected / at Risk (%)
Total   0/37 (0.00%)    
Hide Serious Adverse Events
All Participants
Affected / at Risk (%) # Events
Total   3/37 (8.11%)    
Cardiac disorders   
Acute myocardial infarction  1  1/37 (2.70%)  1
Eye disorders   
Retinal tear  1 [1]  1/37 (2.70%)  1
Gastrointestinal disorders   
Intestinal perforation  1  1/37 (2.70%)  1
Infections and infestations   
Diverticulitis  1  1/37 (2.70%)  1
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
[1]
This event occurred only in an eye receiving the sham procedure.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Participants
Affected / at Risk (%) # Events
Total   37/37 (100.00%)    
Eye disorders   
Anterior chamber cell  1  9/37 (24.32%)  11
Autoimmune uveitis  1 [1]  14/37 (37.84%)  15
Cataract  1 [2]  4/37 (10.81%)  4
Conjunctival haemorrhage  1 [3]  6/37 (16.22%)  7
Conjunctival hyperaemia  1  6/37 (16.22%)  7
Dry eye  1 [4]  2/37 (5.41%)  3
Iridocyclitis  1 [5]  15/37 (40.54%)  17
Iritis  1  2/37 (5.41%)  2
Keratic precipitates  1  13/37 (35.14%)  16
Eye pain  1 [6]  3/37 (8.11%)  4
Intraocular pressure increased  1 [7]  11/37 (29.73%)  13
Vitritis  1  6/37 (16.22%)  6
Vitreous floaters  1  2/37 (5.41%)  3
Vitreous detachment  1  2/37 (5.41%)  2
Vitreal cells  1 [8]  7/37 (18.92%)  7
Visual impairment  1  3/37 (8.11%)  3
Punctate keratitis  1 [9]  15/37 (40.54%)  17
Gastrointestinal disorders   
Abdominal pain upper  1  2/37 (5.41%)  2
Immune system disorders   
Drug hypersensitivity  1  2/37 (5.41%)  2
Infections and infestations   
Nasopharyngitis  1  6/37 (16.22%)  9
Injury, poisoning and procedural complications   
Arthropod bite  1  2/37 (5.41%)  2
Investigations   
Gamma-glutamyl transferase increased  1  8/37 (21.62%)  11
Alanine aminotransferase increased  1  4/37 (10.81%)  4
Aspartate aminotransferase increased  1  2/37 (5.41%)  2
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/37 (5.41%)  2
Nervous system disorders   
Headache  1  4/37 (10.81%)  8
Paraesthesia  1  2/37 (5.41%)  2
Psychiatric disorders   
Depression  1  2/37 (5.41%)  2
Social circumstances   
Alcohol use  1  2/37 (5.41%)  2
Vascular disorders   
Hypertension  1  2/37 (5.41%)  2
1
Term from vocabulary, MedDRA 20.1
Indicates events were collected by systematic assessment
[1]
The verbatim AE term is "intermediate uveitis". 1/14 affected participants experienced this event only in sham-treated eyes.
[2]
1/4 affected participants experienced this event only in sham-treated eyes
[3]
3/6 affected participants experienced this event only in sham-treated eyes.
[4]
1/2 affected participants experienced this event only in sham-treated eyes.
[5]
1/15 affected participants experienced this event only in sham-treated eyes.
[6]
1/3 affected participants experienced this event only in sham-treated eyes.
[7]
1/11 affected participants experienced this event only in sham-treated eyes.
[8]
1/7 affected participants experienced this event only in sham-treated eyes.
[9]
4/15 affected participants experienced this event only in sham-treated eyes.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
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Name/Title: Regulatory Affairs
Organization: GenSight Biologics
Phone: 176217220 ext 0033
EMail: ipengue@gensight-biologics.com
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Responsible Party: GenSight Biologics
ClinicalTrials.gov Identifier: NCT02652780    
Other Study ID Numbers: GS-LHON-CLIN-03B
2015-001266-26 ( EudraCT Number )
First Submitted: January 7, 2016
First Posted: January 12, 2016
Results First Submitted: December 13, 2019
Results First Posted: January 23, 2020
Last Update Posted: January 23, 2020