4D-150 in Patients With Diabetic Macular Edema

• ClinicalTrials.gov Identifier: NCT05930561
• Recruitment Status: Recruiting
• First Posted: July 5, 2023
• Last Update Posted: November 13, 2023
• Sponsor: 4D Molecular Therapeutics
• Information provided by (Responsible Party): 4D Molecular Therapeutics

Tracking Information

• First Submitted Date: June 26, 2023
• First Posted Date: July 5, 2023
• Last Update Posted Date: November 13, 2023
• Actual Study Start Date: August 9, 2023
• Estimated Primary Completion Date: February 29, 2028 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 26, 2023): Annualized number of aflibercept injections in the study eye [ Time Frame: 52 weeks ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 26, 2023)

• Mean cumulative number of aflibercept injections over time [ Time Frame: 52 weeks ]
• Change from baseline in BCVA as assessed using the ETDRS Visual Acuity Chart [ Time Frame: 104 weeks ]
• Change from baseline in CST measured by spectral domain optical coherence tomography (SD-OCT) [ Time Frame: 104 weeks ]
• Percentage of subjects with a ≥2 and ≥3-Step Diabetic Retinopathy Severity (DRS) improvement from baseline on the ETDRS-DRSS [ Time Frame: 104 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures (submitted: June 26, 2023): Incidence and severity of treatment-emergent adverse events and serious adverse events, including clinically significant changes in safety parameters [ Time Frame: 104 weeks ]
• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 4D-150 in Patients With Diabetic Macular Edema
• Official Title: A Phase 2 Randomized, Active-Controlled, Double-masked Trial of Intravitreal 4D-150 Gene Therapy in Adults With Diabetic Macular Edema (SPECTRA)
• Brief Summary: Phase 2 randomized, active-controlled, double-masked, dose-ranging trial in adults with Diabetic Macular Edema (DME).
• Detailed Description: This Phase 2 trial is a prospective, multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of 4D-150 in adults with DME. The trial will be conducted in two parts: Dose Confirmation and Dose Expansion.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

In Dose Confirmation (Part 1), subjects (n=12-18) will be sequentially assigned to one of two open-label dose levels of 4D-150 (n=6-9 per dose level). In Dose Expansion (Part 2), subjects (n=54) will be randomized to receive one of two dose levels of 4D-150 (n=18 per dose level) based on results from Dose Confirmation, or aflibercept control (n=18). Subjects will be masked to treatment arm in Dose Expansion (Part 2).

Masking: Double (Participant, Outcomes Assessor)
Masking Description:

No masking in Dose Confirmation (Part 1). In Dose Expansion (Part 2), participants and outcomes assessors will be masked to treatment arm for the duration of the trial.

Primary Purpose: Treatment

Condition

• Diabetic Macular Edema
• Diabetic Retinopathy

Intervention

• Biological: 4D-150 IVT
  4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept.
• Biological: Aflibercept IVT
  Commercially available Active Comparator
  Other Name: Eylea

Study Arms

• Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 1
  4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
  Intervention: Biological: 4D-150 IVT
• Experimental: 4D-150 Part 1 Dose Confirmation Dose Level 2
  4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
  Intervention: Biological: 4D-150 IVT
• Experimental: 4D-150 Part 2 Dose Expansion Dose Level 1
  4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
  Intervention: Biological: 4D-150 IVT
• Experimental: 4D-150 Part 2 Dose Expansion Dose Level 2
  4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
  Intervention: Biological: 4D-150 IVT
• Active Comparator: 4D-150 Part 2 Dose Expansion Control
  Aflibercept at a fixed regimen will be administered.
  Intervention: Biological: Aflibercept IVT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 26, 2023): 72
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 1, 2028
• Estimated Primary Completion Date: February 29, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• ≥18 years of age
• Type I or Type II diabetes mellitus with macular thickening secondary to DME involving the center of the fovea; diagnosis of DME must be within 2 years of Screening
• Demonstrate clinical response to on-study aflibercept injection in the study eye.
• Decreased visual acuity attributable primarily to DME
• BCVA in the study eye between 25 and 83 ETDRS letters, inclusive (~20/320 and 20/25, respectively) at Screening
• Study eye amenable to IVT injection
• Sufficient clear ocular media, pupil dilation and fixation in the study eye to permit adequate imaging; ability to perform tests of visual and retinal function and structure; and ability to comply with other protocol-specified procedures
• Provide written informed consent

Exclusion Criteria:

• Macular edema in the study eye considered to be secondary to a cause other than DME
• Systemic anti-VEGF treatment (e.g. sunitinib, bevacizumab, pazopanib) within 6 months, or anticipated need for systemic anti-VEGF therapy during study participation
• Systemic corticosteroids (oral, intravenous, intramuscular, intra-articular) or other immunosuppressive medications within 3 months
• Received an investigational drug, agent, device, or therapy (ocular or non-ocular) in the 3 months (or at least 5 half-lives, whichever is longer) prior to 4D-150 administration (Day 1)
• Prior gene therapy (ocular or non-ocular) and/or ocular stem cell therapy in either eye
• Any concurrent ocular condition in the study eye that is likely to require surgical intervention (e.g. cataract surgery) during the 2 year (104 week) study duration

Note: Other inclusion/exclusion criteria apply.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: 4DMT Patient Advocacy; (888) 748-8881; clinicaltrials@4DMT.com

• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT05930561
• Other Study ID Numbers: 4D-150-C002
• 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: Not Provided
• 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: November 2023