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

NCT04483440 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 4D-110-CP-0001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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).

Conditions

Choroideremia

Keywords

CHM; transgene; gene therapy; AAV

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

4D-110 Dose 1

EXPERIMENTAL

4D-110 IVT injection

Biological: 4D-110

4D-110 Dose 2

EXPERIMENTAL

4D-110 IVT injection

Biological: 4D-110

4D-110 Dose 3

EXPERIMENTAL

4D-110 IVT injection

Biological: 4D-110

Interventions

4D-110 BIOLOGICAL

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.

4D-110 Dose 1; 4D-110 Dose 2; 4D-110 Dose 3

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• 4D Molecular Therapeutics: lead

Study Sites (2)

Retina Foundation of the Southwest

Dallas, Texas, 75251, United States

Location

Moran Eye Center, University of Utah

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Choroideremia

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Choroid Diseases; Uveal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked

Study Officials

• Schonmei Lee, MD

  4D Molecular Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 23, 2020
• Study Start: June 2, 2020
• Primary Completion (Estimated): May 26, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)