Back to resultsSafety and Dose Escalation Study of AAV2-hCHM in Subjects With CHM (Choroideremia) Gene Mutations
Primary Purpose
Choroideremia, CHM (Choroideremia) Gene Mutations
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV2-hCHM
Sponsored by
About this trial
This is an interventional treatment trial for Choroideremia focused on measuring Choroideremia, AAV, Gene therapy, CHM, Adeno-associated virus, Adeno-associated viral vector
Eligibility Criteria
Inclusion Criteria:
- Male at least 18 years of age diagnosed with CHM gene mutation
- Central visual field (VF) < 30° in any of the 24 meridians (using Goldmann perimetry III4e isopter) in the eye to be injected
- Any evidence of functioning outer retinal cells within the central 10°
Exclusion Criteria:
- Previous history of ocular inflammatory disease (uveitis)
- Prior intraocular surgery within six months
- Participation in a previous gene therapy research trial within one year of enrollment or participation in any other ocular gene therapy trial
- Participation in a clinical study with an investigational drug in the past six months
- Grossly asymmetrical disease, or other eye morbidity, which may render the contralateral eye ineffective as a control
- Visual acuity < 20/200 on standard ETDRS testing in the eye to be injected
- Presence of disease which may preclude the subject from participation in this trial
- Use of medications known to be neuroprotective or retino-toxic that could potentially interfere with the disease process and/or cause ocular adverse events; individuals who discontinue use of these compounds for 6 months may become eligible
- Identification by the investigator as being unable or unwilling to perform / be compliant with study procedures.
Sites / Locations
- Massachusetts Eye and Ear Infirmary
- University of Pennsylvania
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose Group 1
Dose Group 2
Arm Description
Single, unilateral administration of a single low dose range of AAV2-hCHM.
Single, unilateral administration of a single high dose range of AAV2-hCHM.
Outcomes
Primary Outcome Measures
Safety and tolerability (assessed by physical exam, vital signs, laboratory changes over time, and adverse events)
Safety and tolerability of a single dose of AAV2-hCHM will be assessed by physical exam, vital signs, laboratory changes over time, and adverse events.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02341807
Brief Title
Safety and Dose Escalation Study of AAV2-hCHM in Subjects With CHM (Choroideremia) Gene Mutations
Official Title
A Phase 1/2 Safety Study in Subjects With CHM (Choroideremia) Gene Mutations Using an Adeno-Associated Virus Serotype 2 Vector to Deliver the Normal Human CHM Gene [AAV2-hCHM] to the Retina
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
January 2015 (Actual)
Primary Completion Date
October 12, 2022 (Actual)
Study Completion Date
October 12, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spark Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This clinical study evaluates the safety and tolerability of AAV2-hCHM in subjects with Choroideremia gene mutations. Two dose groups will be evaluated.
Detailed Description
The primary objective is to evaluate the safety and tolerability of subretinal administration of AAV2-hCHM, in an inter-subject group dose escalation in individuals with choroideremia, based on a comprehensive clinical monitoring plan. The secondary objectives are to define the dose of AAV2-hCHM required to achieve stable, or improved, visual function/functional vision and to assess development of immune responses to AAV2 and REP-1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Choroideremia, CHM (Choroideremia) Gene Mutations
Keywords
Choroideremia, AAV, Gene therapy, CHM, Adeno-associated virus, Adeno-associated viral vector
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose Group 1
Arm Type
Experimental
Arm Description
Single, unilateral administration of a single low dose range of AAV2-hCHM.
Arm Title
Dose Group 2
Arm Type
Experimental
Arm Description
Single, unilateral administration of a single high dose range of AAV2-hCHM.
Intervention Type
Biological
Intervention Name(s)
AAV2-hCHM
Intervention Description
Comparison of different dosages of AAV2-hCHM
Primary Outcome Measure Information:
Title
Safety and tolerability (assessed by physical exam, vital signs, laboratory changes over time, and adverse events)
Description
Safety and tolerability of a single dose of AAV2-hCHM will be assessed by physical exam, vital signs, laboratory changes over time, and adverse events.
Time Frame
5 years
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male at least 18 years of age diagnosed with CHM gene mutation
Central visual field (VF) < 30° in any of the 24 meridians (using Goldmann perimetry III4e isopter) in the eye to be injected
Any evidence of functioning outer retinal cells within the central 10°
Exclusion Criteria:
Previous history of ocular inflammatory disease (uveitis)
Prior intraocular surgery within six months
Participation in a previous gene therapy research trial within one year of enrollment or participation in any other ocular gene therapy trial
Participation in a clinical study with an investigational drug in the past six months
Grossly asymmetrical disease, or other eye morbidity, which may render the contralateral eye ineffective as a control
Visual acuity < 20/200 on standard ETDRS testing in the eye to be injected
Presence of disease which may preclude the subject from participation in this trial
Use of medications known to be neuroprotective or retino-toxic that could potentially interfere with the disease process and/or cause ocular adverse events; individuals who discontinue use of these compounds for 6 months may become eligible
Identification by the investigator as being unable or unwilling to perform / be compliant with study procedures.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Director
Organizational Affiliation
Spark Therapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Massachusetts Eye and Ear Infirmary
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19014
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
35714735
Citation
Aleman TS, Huckfeldt RM, Serrano LW, Pearson DJ, Vergilio GK, McCague S, Marshall KA, Ashtari M, Doan TM, Weigel-DiFranco CA, Biron BS, Wen XH, Chung DC, Liu E, Ferenchak K, Morgan JIW, Pierce EA, Eliott D, Bennett J, Comander J, Maguire AM. Adeno-Associated Virus Serotype 2-hCHM Subretinal Delivery to the Macula in Choroideremia: Two-Year Interim Results of an Ongoing Phase I/II Gene Therapy Trial. Ophthalmology. 2022 Oct;129(10):1177-1191. doi: 10.1016/j.ophtha.2022.06.006. Epub 2022 Jun 15.
Results Reference
derived
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Safety and Dose Escalation Study of AAV2-hCHM in Subjects With CHM (Choroideremia) Gene Mutations
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