An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease

April 5, 2024 updated by: 4D Molecular Therapeutics
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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • University of California at San Diego
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh of UPMC
    • Virginia
      • Fairfax, Virginia, United States, 22030
        • Lysosomal & Rare Disorders Research & Treatment Center, Inc

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female ≥ 18 years of age
  2. Pathogenic GLA mutation consistent with Fabry Disease
  3. Confirmed diagnosis of classic or late-onset Fabry disease
  4. 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
  5. Agree to use highly effective contraception

Exclusion Criteria:

  1. Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
  2. eGFR <45 mL/min/1.73 m2
  3. Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
  4. HIV, active or chronic hepatitis B or C,
  5. Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control
  6. History of stroke or transient ischemic attack within the last 12 months, or other significant thromboembolic disease history (e.g. pulmonary embolism)
  7. Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
  8. Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the last 12 months.
  9. Moderately severe to severe cardiovascular disease or uncontrolled hypertension
  10. Left ventricular ejection fraction of <45% on echocardiogram (ECHO)
  11. Currently receiving investigational drug, device or therapy or having ever received gene therapy
  12. History of infusion related response to ERT or any adverse reaction leading to ERT discontinuation
  13. History of cancer within 2 years (exceptions include non-melanoma skin cancer, localized prostate cancer treated with curative intent)
  14. Pregnant or breast-feeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A
Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients
Biological: 4D-310
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).
Experimental: 4D-310 Dose Level 1 - AAV NAb Titer Group B
Single IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients
Biological: 4D-310
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).
Experimental: 4D-310 Dose Expansion
Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients
Biological: 4D-310
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).
Experimental: 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B
Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients
Biological: 4D-310
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events
Time Frame: 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in serum AGA activity
Time Frame: 1 year
Change from baseline in serum AGA activity
1 year
Change from baseline serum globotriaosylsphingosine (lysoGb3)
Time Frame: 1 year
Change from baseline serum globotriaosylsphingosine (lysoGb3)
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4D Molecular Therapeutics

Investigators

  • Study Director: Alan H Cohen, MD, 4D Molecular Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2020

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

June 1, 2030

Study Registration Dates

First Submitted

August 14, 2020

First Submitted That Met QC Criteria

August 17, 2020

First Posted (Actual)

August 20, 2020

Study Record Updates

Last Update Posted (Actual)

April 8, 2024

Last Update Submitted That Met QC Criteria

April 5, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4D-310-C001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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