Safety and Dose-escalation Study of AAV2-hCHM in Participants With CHM (Choroideremia) Gene Mutations

Spark Therapeutics

Status and phase: Completed; Phase 2; Phase 1

Conditions: Choroideremia; CHM (Choroideremia) Gene Mutations

Treatments: Biological: AAV2-hCHM

Study type: Interventional

Funder types: Industry

Identifiers

NCT02341807

AAV2-hCHM-101

Details and patient eligibility

About

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

Full 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).

Enrollment: 15 patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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15 participants in 3 patient groups

Cohort 1: AAV2-hCHM Dose 1

Experimental group

Description:

Single, unilateral subretinal administration of a single low dose range of AAV2-hCHM.

Treatment:

Biological: AAV2-hCHM

Cohort 2: AAV2-hCHM Dose 2

Experimental group

Description:

Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM.

Treatment:

Biological: AAV2-hCHM

Cohort 3 (Expansion Cohort): AAV2-hCHM Dose 2

Experimental group

Description:

Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM.

Treatment:

Biological: AAV2-hCHM