4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration

4D Molecular Therapeutics (4DMT)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Neovascular (Wet) Age-Related Macular Degeneration

Treatments: Biological: 4D-150 IVT; Biological: Aflibercept IVT

Study type: Interventional

Funder types: Industry

Identifiers

NCT05197270

4D-150-C001

Details and patient eligibility

About

Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment.

Substudies will evaluate the safety and tolerability of 4D-150 contralateral eye dosing and characterize vector shedding.

Full description

This Phase 1/2 trial is a prospective, multicenter, Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment who have demonstrated a clinical response consistent with anti-VEGF activity. The trial consists of Dose Escalation, Dose Expansion, Steroid Optimization and Population Extension Cohorts.

After receiving one time administration of 4D-150 by intravitreal injection (IVT), subjects will undergo assessments at monthly intervals for 24 months to assess safety and efficacy outcomes. Only subjects that received 4D-150 will then enter a long-term follow-up (LTFU) period to assess long-term safety of 4D-150 gene therapy and duration of clinical activity through year 5 (60 months).

Eligible subjects who received 4D-150 in the study eye may participate in a sub-study to evaluate one time IVT administration of 4D-150 to the contralateral ("fellow") eye.

Additional subjects will be enrolled in a separate sub-study to characterize the vector shedding profile of one time administration of IVT 4D-150.

In both sub-studies, subjects will undergo regular assessments to assess safety and tolerability through Week 52 and then will enter long-term follow-up for safety evaluation through year 5 (60 months).

Enrollment: 215 estimated patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• 50 years of age

  • Diagnosed with macular CNV secondary to AMD
  • BCVA ETDRS Snellen equivalent for dose escalation and contralateral eye between ~20/32 and ~20/320, or for dose expansion and population extension between ~20/25 and~20/200, for steroid optimization and shedding sub-study between ~20/25 and ~20/640
  • Currently receiving anti-VEGF treatment in the study eye and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening

Contralateral Eye Sub-study-Specific Criteria: Received 4D-150 in study eye-1 at least 6 months prior to Contralateral Sub-study Screening Visit

Contralateral Eye Sub-study-specific Exclusion: Prior adverse event related to 4D-150, required modifications to or reinitiated protocol specified corticosteroid regimen/taper in study eye-1, signs and symptoms of noninfectious intraocular inflammation in either eye

Shedding Sub-study-specific Inclusion Criteria:

S-1. ≥50 years of age S-2. Diagnosed with macular CNV secondary to AMD S-3. BCVA ETDRS Snellen equivalent between ~20/640 and 20/25 S-5. Currently receiving anti-VEGF and has demonstrated a clinical response consistent with anti-VEGF activity within 12 months prior to screening

Shedding Sub-study-specific Exclusion Criteria:

• Any condition preventing visual acuity improvement in the study eye
• Prior treatment with photodynamic therapy or retinal laser in the study eye
• History of uveitis in either eye
• Any other pre-existing eye conditions or surgical complications that would preclude participation in an interventional clinical trial or interfere with the interpretation of study endpoints

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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215 participants in 10 patient groups

4D-150 Dose Escalation up to 4 dose levels

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Dose Expansion Dose 1

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Dose Expansion Dose 2

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Dose Expansion Control

Active Comparator group

Description:

Aflibercept at a fixed regimen will be administered.

Treatment:

Biological: Aflibercept IVT

4D-150 Steroid Optimization

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Population Extension Dose 1

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Population Extension Dose 2

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Population Extension Dose 3

Experimental group

Description:

4D-150 will be administered at the assigned dose

Treatment:

Biological: 4D-150 IVT

4D-150 Contralateral Eye Dose

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT

4D-150 Vector Shedding Dose

Experimental group

Description:

4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.

Treatment:

Biological: 4D-150 IVT