Clinical trial NCT02341807: Safety and Dose-escalation Study of AAV2-hCHM in Participants 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Choroideremia
CHM (Choroideremia) Gene Mutations
Keywords: Choroideremia
AAV
Gene therapy
CHM
Adeno-associated virus
Adeno-associated viral vector
Lead sponsor: Spark Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 15
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study evaluates the safety and tolerability of AAV2-hCHM in participants with Choroideremia gene mutations.

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 adeno-associated virus vector, serotype 2 (AAV2) and Rab escort protein 1 (REP-1).

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 Early Treatment of Diabetic Retinopathy Study (ETDRS) testing in the eye to be injected
* Presence of disease which may preclude the participant 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Number of Participants With Anti-AAV2 Viral Capsid Antibody Titers That Rose Above Baseline At Least Once After Dosing
timeFrame: Up to 2 years
measure: Number of Participants With Cellular Immune Response to AAV2 Through Interferon Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Assay
timeFrame: Up to 2 years
measure: Number of Participants With Cellular Immune Response to Rab Escore Protein-1 (REP-1) Through Interferon Gamma ELISPOT Assay
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
References:
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.