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

• ClinicalTrials.gov Identifier: NCT04483440
• Recruitment Status: Active, not recruiting
• First Posted: July 23, 2020
• Last Update Posted: May 9, 2024
• Sponsor: 4D Molecular Therapeutics
• Information provided by (Responsible Party): 4D Molecular Therapeutics

Tracking Information

• First Submitted Date: July 20, 2020
• First Posted Date: July 23, 2020
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: June 2, 2020
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2023)

Frequency and severity of ocular and systemic adverse events (AEs) [ Time Frame: 24 months ]

Frequency and severity of ocular and systemic AEs including clinically significant changes in ocular evaluations, systemic examinations and laboratory testing.

Original Primary Outcome Measures (submitted: July 20, 2020)

Frequency and severity of ocular and systemic adverse events (AEs) [ Time Frame: 6 months ]

Frequency and severity of ocular and systemic AEs including clinically significant changes in ocular evaluations, systemic examinations and laboratory testing.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation Study of Intravitreal 4D-110 in Patients With Choroideremia
• Official Title: Phase 1 Open-Label, Dose-Escalation Study of the Safety, Tolerability and Preliminary Efficacy of Intravitreal 4D-110 in Patients With Choroideremia
• Brief Summary: 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: 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 three dose levels in male patients with genetically-confirmed CHM.
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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 4 additional patients may be enrolled at that dose level to provide additional safety information.

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Choroideremia

Intervention

Biological: 4D-110

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.

Study Arms

• Experimental: 4D-110 Dose 1
  4D-110 IVT injection
  Intervention: Biological: 4D-110
• Experimental: 4D-110 Dose 2
  4D-110 IVT injection
  Intervention: Biological: 4D-110
• Experimental: 4D-110 Dose 3
  4D-110 IVT injection
  Intervention: Biological: 4D-110

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 18, 2023): 13
• Original Estimated Enrollment (submitted: July 20, 2020): 15
• Estimated Study Completion Date: June 2027
• Estimated Primary Completion Date: June 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04483440
• Other Study ID Numbers: 4D-110-CP-0001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: 4D Molecular Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: 4D Molecular Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Schonmei Lee, MD; 4D Molecular Therapeutics

• PRS Account: 4D Molecular Therapeutics
• Verification Date: May 2024