Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia

Study Overview
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Brief Summary
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This study will evaluate safety, tolerability, and preliminary efficacy of a single intravitreal (IVT) injection of a recombinant adeno-associated virus (AAV) gene therapy, 4D-110, in male patients with genetically-confirmed Choroideremia (CHM).

Detailed Description
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This is an open-label, Phase 1 study to evaluate safety and tolerability as well as preliminary efficacy of a single IVT injection of 4D-110 at two dose levels in male patients with genetically-confirmed CHM.

Official Title
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Phase 1 Open-Label, Dose-Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intravitreal 4D-110 in Patients With Choroideremia

Conditions
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Choroideremia

Intervention / Treatment
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* Biological: 4D-110


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of CHM defined as a pathogenic mutation in the CHM gene, confirmed by genetic testing Both eyes must have ≥ 34 ETDRS letters ( 20/200) Key Exclusion Criteria: Clinically significant, active ocular or peri-ocular infection or inflammation in the study eye Patient has previously received any AAV treatment Ocular conditions or ocular media opacity in either eye that would preclude the planned treatment (i.e. IVT injection) or interfere with the interpretation of study endpoints (e.g. significant lens opacity)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Each dose escalation cohort will initially recruit up to 3 patients to receive a single uniocular intravitreal injection of 4D-110 in a standard 3+3 design. The cohort will be expanded in the event of a dose limiting toxicity (DLT). Once the maximum tolerated dose (MTD)/maximum feasible dose (MFD) has been identified, up to 3 additional patients may be enrolled at that dose level to provide additional safety information.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4D-110 Dose 1<br>4D-110 IVT injection | Biological: 4D-110<br>* 4D-110 drug product developed for gene therapy which comprises an AAV capsid variant (4D-R100) carrying a transgene encoding a codon-optimized human CHM gene.<br>|
| Experimental: 4D-110 Dose 2<br>4D-110 IVT injection | Biological: 4D-110<br>* 4D-110 drug product developed for gene therapy which comprises an AAV capsid variant (4D-R100) carrying a transgene encoding a codon-optimized human CHM gene.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of ocular and systemic adverse events (AEs) | Frequency and severity of ocular and systemic AEs including clinically significant changes in ocular evaluations, systemic examinations and laboratory testing. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHM, transgene, gene therapy, AAV