Trial Outcomes & Findings for Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA) (NCT NCT02781480)

Last Updated: 2021-07-12

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

6 months

Results posted on

2021-07-12

Participant Flow

Participant milestones

Participant milestones
Measure	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)	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)	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)
Overall Study STARTED	9	3	3
Overall Study COMPLETED	9	3	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Dose AAV-RPE65 n=9 Participants 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)	Intermediate Dose AAV-RPE65 n=3 Participants 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)	High Dose AAV-RPE65 n=3 Participants 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)	Total n=15 Participants Total of all reporting groups
Region of Enrollment United States	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Age, Continuous	12.8 years STANDARD_DEVIATION 5.52 • n=5 Participants	19.0 years STANDARD_DEVIATION 2.65 • n=7 Participants	21.0 years STANDARD_DEVIATION 3.00 • n=5 Participants	15.7 years STANDARD_DEVIATION 5.79 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	9 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	9 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized White	7 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment United Kingdom	7 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	13 participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Low Dose AAV-RPE65 n=9 Participants 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)	Intermediate Dose AAV-RPE65 n=3 Participants 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)	High Dose AAV-RPE65 n=3 Participants 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)
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	0 Participants	1 Participants
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	0 Participants	1 Participants
Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event Severe unresponsive inflammation	0 Participants	0 Participants	0 Participants
Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event Infective endophthalmitis	0 Participants	0 Participants	0 Participants
Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event Ocular malignancy	0 Participants	0 Participants	0 Participants
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	0 Participants	0 Participants

Adverse Events

Low Dose AAV-RPE65

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Intermediate Dose AAV-RPE65

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

High Dose AAV-RPE65

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low Dose AAV-RPE65 n=9 participants at risk 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)	Intermediate Dose AAV-RPE65 n=3 participants at risk 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)	High Dose AAV-RPE65 n=3 participants at risk 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)
Eye disorders Uveitis	0.00% 0/9 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	66.7% 2/3 • Number of events 2 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Eye disorders Visual acuity reduced	0.00% 0/9 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.

Other adverse events

Other adverse events
Measure	Low Dose AAV-RPE65 n=9 participants at risk 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)	Intermediate Dose AAV-RPE65 n=3 participants at risk 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)	High Dose AAV-RPE65 n=3 participants at risk 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)
Eye disorders Uveitis	33.3% 3/9 • Number of events 3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 2 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Eye disorders Visual acuity reduced	22.2% 2/9 • Number of events 2 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Eye disorders Anterior chamber inflammation	0.00% 0/9 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Eye disorders Hypotony of eye	11.1% 1/9 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Eye disorders Blurred vision	0.00% 0/9 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Investigations Intraocular pressure increased	11.1% 1/9 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.
Nervous system disorders Visual field defect	0.00% 0/9 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	33.3% 1/3 • Number of events 1 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.	0.00% 0/3 • Within 6 months of ATIMP administration. A serious adverse event that started on or after the start of the administration of ATIMP. Any serious adverse events that occurred after the last administration of ATIMP + 6 months were not considered treatment emergent.

Additional Information

Chief Medical Officer

MeiraGTx

Phone: +1 973 609-2156

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER