4D-150 in Patients With Neovascular (Wet) Age-Related Macular Degeneration
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| ClinicalTrials.gov Identifier: NCT05197270 |
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Recruitment Status :
Recruiting
First Posted : January 19, 2022
Last Update Posted : February 16, 2024
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Sponsor:
4D Molecular Therapeutics
Information provided by (Responsible Party):
4D Molecular Therapeutics
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Brief Summary:
Phase 1/2 dose-escalation and randomized, controlled, masked expansion trial in adults with wet AMD undergoing active anti-VEGF treatment
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Neovascular (Wet) Age-Related Macular Degeneration | Biological: 4D-150 IVT Biological: Aflibercept IVT | Phase 1 Phase 2 |
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, 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).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 150 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Intervention Model Description: | In Dose Escalation, the safety and tolerability of multiple dose levels of 4D-150 will be examined following an open-label, 3+3 dose escalation design (n=3-5 per dose level). In Dose Expansion, subjects (n=50) will be randomized to receive one of 2 dose levels of 4D-150 (n=20 for each dose level) based on results from Dose Escalation, or aflibercept (n=10). In Steroid Optimization (n=up to 40) and Population Extension (n=up to 45) Cohorts, subjects will be assigned sequentially to receive 4D-150 at doses cleared by the DSMC. |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | Dose Escalation will be open-label. During Dose Expansion, outcome assessors will be masked to treatment assignment. Other site personnel (including investigator) and subjects will be unmasked to treatment assignment but will be masked to 4D-150 dose level. The Sponsor and its representatives and the site dose preparer/pharmacist will be unmasked to treatment assignment. Steroid Optimization and Population Extension will be open-label. |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1/2 Dose-Escalation and Randomized, Controlled, Masked Expansion Trial of Intravitreal 4D-150 Gene Therapy in Adults With Neovascular (Wet) Age-Related Macular Degeneration |
| Actual Study Start Date : | December 9, 2021 |
| Estimated Primary Completion Date : | November 2024 |
| Estimated Study Completion Date : | November 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Age-related macular degeneration
MedlinePlus related topics:
Macular Degeneration
| Arm | Intervention/treatment |
|---|---|
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Experimental: 4D-150 Dose Escalation up to 4 dose levels
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
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Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
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Experimental: 4D-150 Dose Expansion Dose 1
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
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Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
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Experimental: 4D-150 Dose Expansion Dose 2
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
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Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
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Active Comparator: 4D-150 Dose Expansion Control
Aflibercept at a fixed regimen will be administered.
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Biological: Aflibercept IVT
Commercially available Active Comparator Other Name: Eylea |
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Experimental: 4D-150 Steroid Optimization
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
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Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
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Experimental: 4D-150 Population Extension Dose 1
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
|
Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
|
Experimental: 4D-150 Population Extension Dose 2
4D-150 will be administered at the assigned dose level as a single dose IVT injection on Day 1.
|
Biological: 4D-150 IVT
4D-150: AAV-based gene therapy comprised of miRNA targeting VEGF-C and codon-optimized sequence encoding aflibercept |
Primary Outcome Measures :
- Incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically significant changes in safety parameters [ Time Frame: 52 weeks ]
Secondary Outcome Measures :
- Time to receiving the first supplemental aflibercept injection [ Time Frame: 52 weeks ]
- Percentage of subjects requiring supplemental aflibercept injections over 52 weeks [ Time Frame: 52 weeks ]
- Number of supplemental aflibercept injections over 52 weeks [ Time Frame: 52 weeks ]
- Change from baseline in BCVA over time (up to 52 weeks) as assessed using the ETDRS Visual Acuity Chart [ Time Frame: 52 weeks ]
- Change from baseline in central subfield thickness (CST) over time (up to 52 weeks) measured by spectral domain optical coherence tomography (SD-OCT) [ Time Frame: 52 weeks ]
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| Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- ≥50 years of age
- Diagnosed with macular CNV secondary to AMD
- BCVA ETDRS Snellen equivalent for dose escalation between ~20/32 and ~20/320, or for dose expansion and population extension between ~20/25 and~20/200, for steroid optimization 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
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05197270
Contacts
| Contact: 4DMT Patient Advocacy | (888) 748-8881 | clinicaltrials@4DMT.com |
Locations
Show 26 study locations
Sponsors and Collaborators
4D Molecular Therapeutics
Investigators
| Study Director: | Chyong Nien, MD | 4D Molecular Therapeutics |
| Responsible Party: | 4D Molecular Therapeutics |
| ClinicalTrials.gov Identifier: | NCT05197270 |
| Other Study ID Numbers: |
4D-150-C001 |
| First Posted: | January 19, 2022 Key Record Dates |
| Last Update Posted: | February 16, 2024 |
| Last Verified: | August 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by 4D Molecular Therapeutics:
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Age-related macular degeneration AMD Exudative AMD Exudative age-related macular degeneration Neovascular AMD Neovascular age-related macular degeneration |
Wet age-related macular degeneration Wet macular degeneration Wet AMD wAMD Retinal gene therapy Intravitreal gene therapy |
Additional relevant MeSH terms:
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Macular Degeneration Retinal Degeneration Retinal Diseases Eye Diseases Aflibercept Angiogenesis Inhibitors |
Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents |