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

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

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

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).

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.