4D-310 in Adults With Fabry Disease and Cardiac Involvement

April 5, 2024 updated by: 4D Molecular Therapeutics

An Open-Label, Phase 1/2a Trial of Gene Therapy 4D-310 in Adults With Fabry Disease and Cardiac Involvement

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 and cardiac involvement

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 and cardiac involvement

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

  • Australia
      • Melbourne, Australia, 3050
        • Royal Melbourne Hospital
      • Perth, Australia, 6000
        • Royal Perth Hospital
  • Taiwan
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital

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

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Adult males and females
  2. Pathogenic GLA mutation consistent with Fabry Disease
  3. Confirmed diagnosis of classic or late-onset Fabry disease with cardiac involvement
  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
4D-310 Dose Level 1 - AAV NAb Titer Group A patients
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 1
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 2
Biological: 4D-310
Single IV administration of 4D-310 at the selected dose
Experimental: 4D-310 Dose Level 1 - AAV NAb Titer Group B
4D-310 Dose Level 1 - AAV NAb titer Group B patients
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 1
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 2
Biological: 4D-310
Single IV administration of 4D-310 at the selected dose
Experimental: 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B
4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 1
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 2
Biological: 4D-310
Single IV administration of 4D-310 at the selected dose
Experimental: 4D-310 Dose Expansion
Dose expansion cohort of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 1
Biological: 4D-310
Single IV administration of 4D-310 Dose Level 2
Biological: 4D-310
Single IV administration of 4D-310 at the selected dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events
Time Frame: 1 year
Incidence and severity of adverse events following a single IV dose of 4D-310
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

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)

October 16, 2022

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2030

Study Registration Dates

First Submitted

November 4, 2022

First Submitted That Met QC Criteria

November 17, 2022

First Posted (Actual)

November 29, 2022

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-C002

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

product manufactured in and exported from the U.S.

Yes

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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