ChoroideremiaPhase 1/2NCT02341807
Safety and Dose-escalation Study of AAV2-hCHM in Participants With CHM (Choroideremia) Gene Mutations
A Phase 1/2 study testing AAV2-hCHM in people with Choroideremia and CHM (Choroideremia) Gene Mutations, run by Spark Therapeutics, Inc. at 3 sites in United States.
Trial summary
This clinical study evaluates the safety and tolerability of AAV2-hCHM in participants with Choroideremia gene mutations. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Choroideremia, CHM (Choroideremia) Gene Mutations
- What is being tested?
- AAV2-hCHM
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 3 sitesUnited States
- Study dates
- 15 Jan 2015to 12 Oct 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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°
Who cannot join
- 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
Show all 9Show fewer
- 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 locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
University of Pennsylvania
Philadelphia, Pennsylvania, 19014
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
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
This clinical study evaluates the safety and tolerability of AAV2-hCHM in participants with Choroideremia gene mutations.
Read the 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).
- Conditions
- Choroideremia, CHM (Choroideremia) Gene Mutations
- Being tested
- AAV2-hCHM
- Keywords
- Choroideremia, AAV, Gene therapy, CHM, Adeno-associated virus, Adeno-associated viral vector
- Medical subject headings
- Choroideremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV2-hCHMBiological
Comparison of different dosages of AAV2-hCHM
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: AAV2-hCHM Dose 1 | Experimental | Single, unilateral subretinal administration of a single low dose range of AAV2-hCHM. Receives: Biological: AAV2-hCHM |
| Cohort 2: AAV2-hCHM Dose 2 | Experimental | Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM. Receives: Biological: AAV2-hCHM |
| Cohort 3 (Expansion Cohort): AAV2-hCHM Dose 2 | Experimental | Single, unilateral subretinal administration of a single high dose range of AAV2-hCHM. Receives: Biological: AAV2-hCHM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
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.
Measured: Up to 5 years
Secondary outcomes (3)
Number of Participants With Anti-AAV2 Viral Capsid Antibody Titers That Rose Above Baseline At Least Once After Dosing
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.
Measured: Up to 2 years
Number of Participants With Cellular Immune Response to AAV2 Through Interferon Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Assay
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.
Measured: Up to 2 years
Number of Participants With Cellular Immune Response to Rab Escore Protein-1 (REP-1) Through Interferon Gamma ELISPOT Assay
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2015 (estimated)
- Study start15 Jan 2015
- Primary completion12 Oct 2022
- Study completion12 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ChoroideremiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Spark Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02341807
- Sponsor's protocol ID
- AAV2-hCHM-101
- Status last verified
- Jan 2024
- First submitted
- 12 Jan 2015
- Last updated
- 25 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 35714735
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02341807
- Acronym / sponsor ID
- AAV2-hCHM-101
- Conditions
- Choroideremia, CHM (Choroideremia) Gene Mutations
- Keywords
- Choroideremia, AAV, Gene therapy, CHM, Adeno-associated virus, Adeno-associated viral vector
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Spark Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jan 2015 (actual)
- Primary completion
- 12 Oct 2022 (actual)
- Study completion
- 12 Oct 2022 (actual)
- First posted
- 19 Jan 2015 (estimated)
- Results
- Posted 2 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: AAV2-hCHM Dose 1 | Experimental | Biological: AAV2-hCHMSingle, unilateral subretinal administration of a single low dose range of AAV2-hCHM. |
| Cohort 2: AAV2-hCHM Dose 2 | Experimental | Biological: AAV2-hCHMSingle, unilateral subretinal administration of a single high dose range of AAV2-hCHM. |
| Cohort 3 (Expansion Cohort): AAV2-hCHM Dose 2 | Experimental | Biological: AAV2-hCHMSingle, unilateral subretinal administration of a single high dose range of AAV2-hCHM. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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°
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV2-hCHMComparison of different dosages of AAV2-hCHM | Biological | Cohort 1: AAV2-hCHM Dose 1, Cohort 2: AAV2-hCHM Dose 2, Cohort 3 (Expansion Cohort): AAV2-hCHM Dose 2 |
Primary outcome
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.
3 secondary outcomes
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 With Cellular Immune Response to AAV2 Through Interferon Gamma Enzyme-linked Immunosorbent Spot (ELISpot) Assay
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35714735Aleman 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.
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Choroideremia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AAV2-hCHM in people with Choroideremia and CHM (Choroideremia) Gene Mutations, run by Spark Therapeutics, Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02341807, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.