Leber Congenital Amaurosis
Conditions
Brief summary
A clinical trial of AAV2/5 vector for patients with Defects in RPE65
Detailed description
A dose escalation and dose expansion (Phase I/II) trial of adults and children with retinal dystrophy associated with defects in RPE65. ATIMP will be administered to one eye only in a single sub-retinal procedure
Interventions
BIOLOGICALAAV RPE65
Comparison of different dosages of AAV RPE65
Sponsors
MeiraGTx UK II Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
AAV2/5-OPTIRPE65
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Aged 3 years or older * Early-onset severe retinal dystrophy consistent with RPE65 deficiency Key
Exclusion criteria
* Females who are pregnant or breastfeeding * Have participated in another research study involving an investigational therapy for ocular disease within the last 6 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | 6 months | Safety was defined as an advanced therapy investigational medicinal product (ATIMP) related: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more. * Severe unresponsive inflammation. * Infective endophthalmitis. * Ocular malignancy. * Grade III or above non-ocular suspected unexpected serious adverse reaction (SUSAR). |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Low Dose AAV-RPE65 Unilateral sub-retinal injection of AAV2/5-OPTIRPE65 in a total volume of no more than 1mL at low dose (1 x 10\^11 vg/mL) | 9 |
| Intermediate Dose AAV-RPE65 Unilateral sub-retinal injection of AAV2/5-OPTIRPE65 in a total volume of no more than 1mL at intermediate dose (3 x 10\^11 vg/mL) | 3 |
| High Dose AAV-RPE65 Unilateral sub-retinal injection of AAV2/5-OPTIRPE65 in a total volume of no more than 1mL at high dose (1 x 10\^12 vg/mL) | 3 |
| Total | 15 |
Baseline characteristics
| Characteristic | Total | Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 |
|---|---|---|---|---|
| Age, Continuous | 15.7 years STANDARD_DEVIATION 5.79 | 12.8 years STANDARD_DEVIATION 5.52 | 19.0 years STANDARD_DEVIATION 2.65 | 21.0 years STANDARD_DEVIATION 3 |
| Race/Ethnicity, Customized Asian | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 14 Participants | 9 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 12 Participants | 7 Participants | 3 Participants | 2 Participants |
| Region of Enrollment United Kingdom | 13 participants | 7 participants | 3 participants | 3 participants |
| Region of Enrollment United States | 2 participants | 2 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 5 / 9 | 2 / 3 | 3 / 3 |
| serious Total, serious adverse events | 0 / 9 | 2 / 3 | 1 / 3 |
Outcome results
Primary
Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event
Safety was defined as an advanced therapy investigational medicinal product (ATIMP) related: * Reduction in visual acuity by 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters or more. * Severe unresponsive inflammation. * Infective endophthalmitis. * Ocular malignancy. * Grade III or above non-ocular suspected unexpected serious adverse reaction (SUSAR).
Time frame: 6 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Grade III or above non-ocular SUSAR | 0 Participants |
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Severe unresponsive inflammation | 0 Participants |
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Ocular malignancy | 0 Participants |
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Number of subjects with dose limiting events. | 0 Participants |
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Infective endophthalmitis | 0 Participants |
| Low Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Reduction in visual acuity by 15 ETDRS | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Infective endophthalmitis | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Ocular malignancy | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Reduction in visual acuity by 15 ETDRS | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Grade III or above non-ocular SUSAR | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Number of subjects with dose limiting events. | 0 Participants |
| Intermediate Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Severe unresponsive inflammation | 0 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Severe unresponsive inflammation | 0 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Number of subjects with dose limiting events. | 1 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Reduction in visual acuity by 15 ETDRS | 1 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Grade III or above non-ocular SUSAR | 0 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Infective endophthalmitis | 0 Participants |
| High Dose AAV-RPE65 | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event | Ocular malignancy | 0 Participants |