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

January 23, 2024 updated by: Spark Therapeutics

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts Eye and Ear Infirmary
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Children's Hospital of Philadelphia
      • Philadelphia, Pennsylvania, United States, 19014
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: AAV2-hCHM Dose 1
Single, unilateral subretinal administration of a single low dose range of AAV2-hCHM.
Biological: AAV2-hCHM
Comparison of different dosages of AAV2-hCHM
Experimental: Cohort 2: AAV2-hCHM Dose 2
Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM.
Biological: AAV2-hCHM
Comparison of different dosages of AAV2-hCHM
Experimental: Cohort 3 (Expansion Cohort): AAV2-hCHM Dose 2
Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM.
Biological: AAV2-hCHM
Comparison of different dosages of AAV2-hCHM

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Up to 5 years
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were AEs that occurred on or after the day of study drug administration. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Anti-AAV2 Viral Capsid Antibody Titers That Rose Above Baseline At Least Once After Dosing
Time Frame: Up to 2 years
Number of participants who were found to have quantifiable levels (above 1.55 micrograms [μg]/milliliter [mL]) of Anti-AAV2 viral capsid antibodies titer in the blood at least 1 study visit up to 2 years were reported.
Up to 2 years
Number of Participants With Cellular Immune Response to AAV2 Through Interferon Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Assay
Time Frame: Up to 2 years
Interferon gamma ELISpot assays were used to evaluate the cellular immune response to AAV2 antigen in collected peripheral blood mononuclear cell (PBMC) samples. Number of participants who demonstrated immune response to the AAV2 antigen were reported.
Up to 2 years
Number of Participants With Cellular Immune Response to Rab Escore Protein-1 (REP-1) Through Interferon Gamma ELISPOT Assay
Time Frame: Up to 2 years
Interferon gamma ELISpot assays were used to evaluate the cellular immune response to REP-1 antigen in collected PBMC samples. Number of participants who demonstrated immune response to the REP-1 antigen were reported.
Up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Spark Therapeutics

Investigators

  • Study Director: Clinical Director, Spark Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 15, 2015

Primary Completion (Actual)

October 12, 2022

Study Completion (Actual)

October 12, 2022

Study Registration Dates

First Submitted

January 12, 2015

First Submitted That Met QC Criteria

January 14, 2015

First Posted (Estimated)

January 19, 2015

Study Record Updates

Last Update Posted (Estimated)

January 25, 2024

Last Update Submitted That Met QC Criteria

January 23, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAV2-hCHM-101

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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