Trial Outcomes & Findings for Gene Therapy for Achromatopsia (CNGA3) (NCT NCT03758404)
NCT ID: NCT03758404
Last Updated: 2022-12-01
Results Overview
The primary outcome is defined as any of the below occurring during the 6 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Products (ATIMP), not surgery alone: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more that fails to resolve to within 15 letters of baseline in a 4-week period once prophylactic treatment commences * Severe unresponsive inflammation * Infective endophthalmitis * Ocular malignancy * Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
11 participants
Primary outcome timeframe
6 Weeks
Results posted on
2022-12-01
Participant Flow
Participants were recruited from two medical centers between 12 August 2019 (date first participant signed informed) and 19 November 2020 (date last participant signed informed consent). A total of 11 participants were enrolled in the study.
Participant milestones
| Measure |
Low Dose AAV - CNGA3
Subretinal administration of a single low dose adeno-associated virus AAV-CNGA3
AAV-CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
Subretinal administration of a single intermediate dose adeno-associated virus AAV-CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
Subretinal administration of a single high dose adeno-associated virus AAV-CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
5
|
|
Overall Study
COMPLETED
|
3
|
3
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Gene Therapy for Achromatopsia (CNGA3)
Baseline characteristics by cohort
| Measure |
Low Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=5 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
|
Region of Enrollment
United Kingdom
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
9 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 6 WeeksPopulation: The safety analysis set included all enrolled participants.
The primary outcome is defined as any of the below occurring during the 6 weeks following administration, at least possibly related to the Advanced Therapy Investigational Medicinal Products (ATIMP), not surgery alone: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more that fails to resolve to within 15 letters of baseline in a 4-week period once prophylactic treatment commences * Severe unresponsive inflammation * Infective endophthalmitis * Ocular malignancy * Grade III or above non-ocular Suspected Unexpected Serious Adverse Reaction (SUSAR)
Outcome measures
| Measure |
Low Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=5 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Overall
Subretinal administration of a single low, intermediate, or high dose AAV CNGA3
adeno-associated virus vector AAV- CNGA3: Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
|
|---|---|---|---|---|
|
Number of Participants Meeting the Primary Outcome Defined as Any of the Below Events Occurring During the 6 Weeks Following Administration, at Least Possibly Related to the Advanced Therapy Investigational Medicinal Products (ATIMP), Not Surgery Alone.
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: All of the 11 participants performed the visual acuity assessment at baseline and Week 24.
Change from baseline to Week 24 in best corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study (ETDRS) chart letter score. The direction of improvement from baseline is an increase in the number of ETDRS letters read over time.
Outcome measures
| Measure |
Low Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=5 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Overall
n=11 Participants
Subretinal administration of a single low, intermediate, or high dose AAV CNGA3
adeno-associated virus vector AAV- CNGA3: Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
|
|---|---|---|---|---|
|
Improvements in Visual Function as Assessed by Visual Acuity
|
0.22 number of ETDRS letters
Interval -0.7 to 1.3
|
2.44 number of ETDRS letters
Interval 0.0 to 4.7
|
2.40 number of ETDRS letters
Interval -1.0 to 5.0
|
1.82 number of ETDRS letters
Interval -1.0 to 5.0
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: Six of the 11 participants had mean retinal sensitivity data available at both baseline and Week 24 in the treated eye.
Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.
Outcome measures
| Measure |
Low Dose AAV - CNGA3
n=1 Participants
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=1 Participants
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=4 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Overall
n=6 Participants
Subretinal administration of a single low, intermediate, or high dose AAV CNGA3
adeno-associated virus vector AAV- CNGA3: Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
|
|---|---|---|---|---|
|
Improvements in Retinal Function as Assessed by Static Perimetry
|
1.17 decibel
|
-1.83 decibel
|
0.15 decibel
Interval -0.3 to 0.9
|
-0.01 decibel
Interval -1.8 to 1.2
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: EQ-VAS data were available for 6 of the 9 children/adolescents enrolled in the study.
Change from baseline to Week 24 in EuroQol Visual Analogue Scale (EQ-VAS) in children and adolescents. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative reflects worsening.
Outcome measures
| Measure |
Low Dose AAV - CNGA3
n=1 Participants
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=3 Participants
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=2 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Overall
n=6 Participants
Subretinal administration of a single low, intermediate, or high dose AAV CNGA3
adeno-associated virus vector AAV- CNGA3: Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
|
|---|---|---|---|---|
|
Quality of Life Measured by QoL Questionnaires in Children and Adolescents
|
-15 units on a scale
|
18.3 units on a scale
Interval -1.0 to 50.0
|
8.0 units on a scale
Interval 0.0 to 16.0
|
9.3 units on a scale
Interval -15.0 to 50.0
|
SECONDARY outcome
Timeframe: 6 MonthsPopulation: EQ-VAS data were available for both adults enrolled in the study.
Change from baseline to Week 24 in EuroQol Visual Analogue Scale (EQ-VAS) in adults. EQ-VAS uses a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state. A positive change from baseline reflects improvement and a negative reflects worsening.
Outcome measures
| Measure |
Low Dose AAV - CNGA3
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=2 Participants
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Overall
n=2 Participants
Subretinal administration of a single low, intermediate, or high dose AAV CNGA3
adeno-associated virus vector AAV- CNGA3: Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
|
|---|---|---|---|---|
|
Quality of Life Measured by QoL Questionnaires in Adults
|
—
|
—
|
1.5 units on a scale
Interval -7.0 to 10.0
|
1.5 units on a scale
Interval -7.0 to 10.0
|
Adverse Events
Low Dose AAV - CNGA3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Intermediate Dose AAV - CNGA3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
High Dose AAV - CNGA3
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Low Dose AAV - CNGA3
n=3 participants at risk
Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
Intermediate Dose AAV - CNGA3
n=3 participants at risk
Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
High Dose AAV - CNGA3
n=5 participants at risk
Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene
|
|---|---|---|---|
|
Eye disorders
Conjunctival haemorrhage
|
100.0%
3/3 • 6 months
|
100.0%
3/3 • 6 months
|
100.0%
5/5 • 6 months
|
|
Eye disorders
Visual acuity reduced
|
100.0%
3/3 • 6 months
|
100.0%
3/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Eye disorders
Conjunctival hyperaemia
|
33.3%
1/3 • 6 months
|
100.0%
3/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Eye disorders
Lenticular opacities
|
33.3%
1/3 • 6 months
|
100.0%
3/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Eye disorders
Ocular discomfort
|
33.3%
1/3 • 6 months
|
33.3%
1/3 • 6 months
|
80.0%
4/5 • 6 months
|
|
Eye disorders
Eye inflammation
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Eye disorders
Eye pain
|
33.3%
1/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Eye disorders
Eye pruritus
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
40.0%
2/5 • 6 months
|
|
Eye disorders
Subconjunctival cyst
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Eye disorders
Chorioretinal folds
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Eye disorders
Foreign body sensation in eyes
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Eye disorders
Iridocyclitis
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Eye disorders
Photophobia
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Eye disorders
Punctate keratitis
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Eye disorders
Retinal disorder
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Eye disorders
Uveitis
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Eye disorders
Vitreous floaters
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
Intraocular pressure increased
|
33.3%
1/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Investigations
Blood glucose increased
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Investigations
Intraocular pressure decreased
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Investigations
Slit-lamp tests abnormal
|
0.00%
0/3 • 6 months
|
33.3%
1/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Vomiting
|
100.0%
3/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Endocrine disorders
Hyperlipidaemia
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Endocrine disorders
Type 2 diabetes mellitus
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Ear and labyrinth disorders
Ear pain
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/3 • 6 months
|
0.00%
0/3 • 6 months
|
20.0%
1/5 • 6 months
|
|
Infections and infestations
Rhinitis
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Injury, poisoning and procedural complications
Tenon's cyst
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Syncope
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
33.3%
1/3 • 6 months
|
0.00%
0/3 • 6 months
|
0.00%
0/5 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place