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

NCT ID: NCT04519749

Last Updated: 2024-04-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-01

Study Completion Date

2030-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Fabry Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

4D-310

Intervention Type BIOLOGICAL

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).

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

Group Type EXPERIMENTAL

4D-310

Intervention Type BIOLOGICAL

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).

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

Group Type EXPERIMENTAL

4D-310

Intervention Type BIOLOGICAL

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).

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

Group Type EXPERIMENTAL

4D-310

Intervention Type BIOLOGICAL

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).

Interventions

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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).

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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4D Molecular Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan H Cohen, MD

Role: STUDY_DIRECTOR

4D Molecular Therapeutics

Locations

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University of California at San Diego

La Jolla, California, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Lysosomal & Rare Disorders Research & Treatment Center, Inc

Fairfax, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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4D-310-C001

Identifier Type: -

Identifier Source: org_study_id

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