OPTIRPE65: Clinical Trial of Gene Therapy for the Treatment of Leber Congenital Amaurosis (LCA)
Sponsor
MeiraGTx UK II Ltd (Industry)
Overall Status
Completed
CT.gov ID
NCT02781480
Collaborator
(none)
15
2
3
32
7.5
0.2
Study Details
Study Description
Brief Summary
A clinical trial of AAV2/5 vector for patients with Defects in RPE65
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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
Study Design
Study Type:
Interventional
Actual Enrollment
:
15 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
AAV2/5-OPTIRPE65AAV2/5-OPTIRPE65
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Multi-centre, Phase I/II Dose Escalation Trial of an Adeno Associated Virus Vector for Gene Therapy of Adults And Children With Retinal Dystrophy Associated With Defects in RPE65 (LCA)
Study Start Date
:
Apr 1, 2016
Actual Primary Completion Date
:
Dec 1, 2018
Actual Study Completion Date
:
Dec 1, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Low dose AAV-RPE65 Subretinal administration of a single low dose of range AAV-RPE65 |
Biological: AAV RPE65
Comparison of different dosages of AAV RPE65
|
| Experimental: Intermediate dose AAV-RPE65 Subretinal administration of a single intermediate dose of range AAV-RPE65 |
Biological: AAV RPE65
Comparison of different dosages of AAV RPE65
|
| Experimental: High dose AAV-RPE65 Subretinal administration of a single high dose of range AAV-RPE65 |
Biological: AAV RPE65
Comparison of different dosages of AAV RPE65
|
Outcome Measures
Primary Outcome Measures
- 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).
Eligibility Criteria
Criteria
Ages Eligible for Study:
3 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kellogg Eye Centre, University of Michigan | Ann Arbor | Michigan | United States | 48105 |
| 2 | Moorfields Eye Hospital NHS Foundation Trust | London | United Kingdom | EC1V 2PD |
Sponsors and Collaborators
- MeiraGTx UK II Ltd
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
MeiraGTx UK II Ltd
ClinicalTrials.gov Identifier:
NCT02781480
Other Study ID Numbers:
- MGT003
First Posted:
May 24, 2016
Last Update Posted:
Jul 12, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 |
|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) |
| Period Title: Overall Study | |||
| STARTED | 9 | 3 | 3 |
| COMPLETED | 9 | 3 | 3 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 | Total |
|---|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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 of all reporting groups |
| Overall Participants | 9 | 3 | 3 | 15 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
12.8
(5.52)
|
19.0
(2.65)
|
21.0
(3.00)
|
15.7
(5.79)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
7
77.8%
|
2
66.7%
|
0
0%
|
9
60%
|
| Male |
2
22.2%
|
1
33.3%
|
3
100%
|
6
40%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
1
33.3%
|
0
0%
|
1
6.7%
|
| Not Hispanic or Latino |
9
100%
|
2
66.7%
|
3
100%
|
14
93.3%
|
| Black or African American |
0
0%
|
0
0%
|
1
33.3%
|
1
6.7%
|
| Asian |
2
22.2%
|
0
0%
|
0
0%
|
2
13.3%
|
| White |
7
77.8%
|
3
100%
|
2
66.7%
|
12
80%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
2
22.2%
|
0
0%
|
0
0%
|
2
13.3%
|
| United Kingdom |
7
77.8%
|
3
100%
|
3
100%
|
13
86.7%
|
Outcome Measures
| Title | Overall Safety of Adeno-Associated Virus Vector (AAV-OPTIRPE65) - Number of Participants With a Safety Event |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 |
|---|---|---|---|
| Arm/Group Description | 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) | 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) | 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) |
| Measure Participants | 9 | 3 | 3 |
| Number of subjects with dose limiting events. |
0
0%
|
0
0%
|
1
33.3%
|
| Reduction in visual acuity by 15 ETDRS |
0
0%
|
0
0%
|
1
33.3%
|
| Severe unresponsive inflammation |
0
0%
|
0
0%
|
0
0%
|
| Infective endophthalmitis |
0
0%
|
0
0%
|
0
0%
|
| Ocular malignancy |
0
0%
|
0
0%
|
0
0%
|
| Grade III or above non-ocular SUSAR |
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | Within 6 months of ATIMP administration. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||
| Arm/Group Title | Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 | |||
| Arm/Group Description | 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) | 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) | 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) | |||
All Cause Mortality |
||||||
| Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 0/3 (0%) | 0/3 (0%) | |||
Serious Adverse Events |
||||||
| Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/9 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | |||
| Eye disorders | ||||||
| Uveitis | 0/9 (0%) | 0 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 1 |
| Visual acuity reduced | 0/9 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| Low Dose AAV-RPE65 | Intermediate Dose AAV-RPE65 | High Dose AAV-RPE65 | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/9 (55.6%) | 2/3 (66.7%) | 3/3 (100%) | |||
| Eye disorders | ||||||
| Uveitis | 3/9 (33.3%) | 3 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 |
| Visual acuity reduced | 2/9 (22.2%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Anterior chamber inflammation | 0/9 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 |
| Hypotony of eye | 1/9 (11.1%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Blurred vision | 0/9 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
| Investigations | ||||||
| Intraocular pressure increased | 1/9 (11.1%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 |
| Nervous system disorders | ||||||
| Visual field defect | 0/9 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Chief Medical Officer |
|---|---|
| Organization | MeiraGTx |
| Phone | +1 973 609-2156 |
| robert.zeldin@meiragtx.com |
Responsible Party:
MeiraGTx UK II Ltd
ClinicalTrials.gov Identifier:
NCT02781480
Other Study ID Numbers:
- MGT003
First Posted:
May 24, 2016
Last Update Posted:
Jul 12, 2021
Last Verified:
Jun 1, 2021