An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
1 other identifier
interventional
18
1 country
4
Brief Summary
This is a prospective multicenter, open-label, dose-escalation trial to assess the safety, tolerability, and pharmacodynamics of 4D-310 following a single IV administration. The study population is comprised of adult males and females with Fabry Disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Sep 2020
Longer than P75 for phase_1
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 14, 2020
CompletedFirst Posted
Study publicly available on registry
August 20, 2020
CompletedStudy Start
First participant enrolled
September 1, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2030
ExpectedApril 8, 2024
April 1, 2024
5.3 years
August 14, 2020
April 5, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence and severity of adverse events
Safety and tolerability of 4D-310 following a single IV dose, as assessed by incidence and severity of adverse events, serious adverse events and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters
1 year
Secondary Outcomes (2)
Change from baseline in serum AGA activity
1 year
Change from baseline serum globotriaosylsphingosine (lysoGb3)
1 year
Study Arms (4)
4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A
EXPERIMENTALSingle IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients
4D-310 Dose Level 1 - AAV NAb Titer Group B
EXPERIMENTALSingle IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients
4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B
EXPERIMENTALSingle IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients
4D-310 Dose Expansion
EXPERIMENTALDose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients
Interventions
4D-310 is a novel adeno-associated virus (AAV) gene therapy comprised of two active components: the capsid (4D-C102) and the transgene cassette, which encodes a codon-optimized full length human GLA transgene driven by the CAG promoter. 4D-310 has been engineered so that it cannot replicate (replication incompetent).
Eligibility Criteria
You may qualify if:
- Male or female ≥ 18 years of age
- Pathogenic GLA mutation consistent with Fabry Disease
- Confirmed diagnosis of classic or late-onset Fabry disease
- Individuals on ERT must be on a stable dose for at least 6 months (and a minimum of 12 months total exposure) prior to study enrollment
- Agree to use highly effective contraception
You may not qualify if:
- Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
- eGFR \<45 mL/min/1.73 m2
- Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
- HIV, active or chronic hepatitis B or C,
- Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control
- History of stroke or transient ischemic attack within the last 12 months, or other significant thromboembolic disease history (e.g. pulmonary embolism)
- Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
- Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the last 12 months.
- Moderately severe to severe cardiovascular disease or uncontrolled hypertension
- Left ventricular ejection fraction of \<45% on echocardiogram (ECHO)
- Currently receiving investigational drug, device or therapy or having ever received gene therapy
- History of infusion related response to ERT or any adverse reaction leading to ERT discontinuation
- History of cancer within 2 years (exceptions include non-melanoma skin cancer, localized prostate cancer treated with curative intent)
- Pregnant or breast-feeding
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (4)
University of California at San Diego
La Jolla, California, 92037, United States
Emory University
Atlanta, Georgia, 30322, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Lysosomal & Rare Disorders Research & Treatment Center, Inc
Fairfax, Virginia, 22030, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Alan H Cohen, MD
4D Molecular Therapeutics
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 14, 2020
First Posted
August 20, 2020
Study Start
September 1, 2020
Primary Completion
January 1, 2026
Study Completion (Estimated)
June 1, 2030
Last Updated
April 8, 2024
Record last verified: 2024-04
Data Sharing
- IPD Sharing
- Will not share