Achromatopsia
Conditions
Brief summary
A clinical trial of adeno-associated virus vector (AAV) CNGA3 retinal gene therapy for patients with achromatopsia
Detailed description
CNGA3 retinal gene therapy for patients with achromatopsia
Interventions
BIOLOGICALadeno-associated virus vector AAV- CNGA3
Adeno-associated virus (AAV) gene therapy for defects in CNGA3 gene
Sponsors
Janssen Research & Development, LLC
MeiraGTx UK II Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Are aged years or over * Have achromatopsia confirmed by a retinal specialist investigator
Exclusion criteria
* Are females who are pregnant or breastfeeding * Have participated in another research study involving an investigational medicinal therapy for ocular disease within the last 6 months * Have any other condition that the investigator considers makes them inappropriate for entry into the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 6 Weeks | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvements in Visual Function as Assessed by Visual Acuity | 6 Months | 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. |
| Improvements in Retinal Function as Assessed by Static Perimetry | 6 Months | Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity. |
| Quality of Life Measured by QoL Questionnaires in Children and Adolescents | 6 Months | 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. |
| Quality of Life Measured by QoL Questionnaires in Adults | 6 Months | 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. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Low Dose AAV - CNGA3 Subretinal administration of a single low dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene | 3 |
| Intermediate Dose AAV - CNGA3 Subretinal administration of a single intermediate dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene | 3 |
| High Dose AAV - CNGA3 Subretinal administration of a single high dose AAV - CNGA3
AAV- CNGA3: AAV gene therapy for defects in CNGA3 gene | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Low Dose AAV - CNGA3 | Intermediate Dose AAV - CNGA3 | High Dose AAV - CNGA3 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United Kingdom | 3 participants | 3 participants | 3 participants | 9 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 0 / 5 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 5 / 5 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 5 |
Outcome results
Primary
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.
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)
Time frame: 6 Weeks
Population: The safety analysis set included all enrolled participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Dose AAV - CNGA3 | 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 |
| Intermediate Dose AAV - CNGA3 | 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 |
| High Dose AAV - CNGA3 | 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 |
Secondary
Improvements in Retinal Function as Assessed by Static Perimetry
Change from baseline to Week 24 in mean retinal sensitivity in the treated eye. The direction of improvement is an increase in sensitivity.
Time frame: 6 Months
Population: Six of the 11 participants had mean retinal sensitivity data available at both baseline and Week 24 in the treated eye.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Dose AAV - CNGA3 | Improvements in Retinal Function as Assessed by Static Perimetry | 1.17 decibel |
| Intermediate Dose AAV - CNGA3 | Improvements in Retinal Function as Assessed by Static Perimetry | -1.83 decibel |
| High Dose AAV - CNGA3 | Improvements in Retinal Function as Assessed by Static Perimetry | 0.15 decibel |
| Overall | Improvements in Retinal Function as Assessed by Static Perimetry | -0.01 decibel |
Secondary
Improvements in Visual Function as Assessed by Visual Acuity
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.
Time frame: 6 Months
Population: All of the 11 participants performed the visual acuity assessment at baseline and Week 24.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Dose AAV - CNGA3 | Improvements in Visual Function as Assessed by Visual Acuity | 0.22 number of ETDRS letters |
| Intermediate Dose AAV - CNGA3 | Improvements in Visual Function as Assessed by Visual Acuity | 2.44 number of ETDRS letters |
| High Dose AAV - CNGA3 | Improvements in Visual Function as Assessed by Visual Acuity | 2.40 number of ETDRS letters |
| Overall | Improvements in Visual Function as Assessed by Visual Acuity | 1.82 number of ETDRS letters |
Secondary
Quality of Life Measured by QoL Questionnaires in Adults
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.
Time frame: 6 Months
Population: EQ-VAS data were available for both adults enrolled in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Dose AAV - CNGA3 | Quality of Life Measured by QoL Questionnaires in Adults | 1.5 units on a scale |
| Overall | Quality of Life Measured by QoL Questionnaires in Adults | 1.5 units on a scale |
Secondary
Quality of Life Measured by QoL Questionnaires in Children and Adolescents
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.
Time frame: 6 Months
Population: EQ-VAS data were available for 6 of the 9 children/adolescents enrolled in the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Low Dose AAV - CNGA3 | Quality of Life Measured by QoL Questionnaires in Children and Adolescents | -15 units on a scale |
| Intermediate Dose AAV - CNGA3 | Quality of Life Measured by QoL Questionnaires in Children and Adolescents | 18.3 units on a scale |
| High Dose AAV - CNGA3 | Quality of Life Measured by QoL Questionnaires in Children and Adolescents | 8.0 units on a scale |
| Overall | Quality of Life Measured by QoL Questionnaires in Children and Adolescents | 9.3 units on a scale |