An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adult Males With Fabry Disease
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ClinicalTrials.gov Identifier: NCT04519749 |
Recruitment Status :
Recruiting
First Posted : August 20, 2020
Last Update Posted : April 4, 2022
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Fabry Disease | Biological: 4D-310 | Phase 1 Phase 2 |
Study Type : | Interventional |
Estimated Enrollment : | 18 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adult Males With Fabry Disease |
Actual Study Start Date : | September 1, 2020 |
Estimated Primary Completion Date : | February 2024 |
Estimated Study Completion Date : | April 2027 |

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 Level 2 - AAV NAb Titer Group A
Single IV administration of 4D-310 Dose Level 2 - 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 2 - AAV NAb Titer Group B
Single IV administration of 4D-310 at Dose Level 2 in 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). |
- 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
- Change from baseline in serum AGA activity [ Time Frame: 1 year ]Change from baseline in serum AGA activity
- Change from baseline serum globotriaosylsphingosine (lysoGb3) [ Time Frame: 1 year ]Change from baseline serum globotriaosylsphingosine (lysoGb3)

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Male |
Gender Based Eligibility: | Yes |
Gender Eligibility Description: | Males only |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Male ≥ 18 years of age
- Pathogenic GLA mutation consistent with Fabry Disease
- Confirmed diagnosis of classic Fabry disease with one or more clinical characteristics: acroparesthesia, hypohidrosis, angiokeratoma or cornea verticillata, or late-onset Fabry disease with left ventricular hypertrophy.
- 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
Exclusion Criteria:
- Presence of high titer NAb to 4D-310 capsid
- Presence of high antibody titer to AGA
- eGFR <45 mL/min/1.73 m2
- Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
- Either history of, or a positive serology test at Screening for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCAb), or human immunodeficiency virus (HIV)
- Evidence of liver disease
- Severe pulmonary disease
- 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
- 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)
- Presence of intercurrent illness or other extenuating circumstance including active infection, active illicit drug or alcohol abuse; that might limit compliance with study requirements; morbid obesity with a BMI of >=35; or in the Investigator's assessment would place the subject at an unacceptable risk or confound interpretation of results

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): NCT04519749
Contact: Molly Nie | 510-505-2680 | clinicaltrials@4DMT.com |
United States, Alabama | |
University of Alabama at Birmingham | Recruiting |
Birmingham, Alabama, United States, 35294 | |
Contact: Christina Singleton, RN 205-975-2935 csingleton@uabmc.edu | |
Principal Investigator: Eric Wallace, MD, FASN | |
United States, California | |
University of California at Los Angeles | Not yet recruiting |
Los Angeles, California, United States, 90025 | |
Contact: Ariana Apopei 310-954-2692 Rastogiresearch@mednet.ucla.edu | |
Principal Investigator: Anjay Rastogi, MD PhD | |
United States, Georgia | |
Emory University | Recruiting |
Atlanta, Georgia, United States, 30322 | |
Contact: Dawn Jacob Laney 404-778-8518 dawn.laney@emory.edu | |
Principal Investigator: William Wilcox, MD, PhD | |
United States, Pennsylvania | |
Children's Hospital of Pittsburgh of UPMC | Recruiting |
Pittsburgh, Pennsylvania, United States, 15224 | |
Contact: Nadene Henderson 412-692-3475 nadene.henderson@chp.edu | |
Contact: Michele Graham michele.graham@chp.edu | |
Principal Investigator: Gerard Vockley, MD, PhD | |
United States, Utah | |
University of Utah | Recruiting |
Salt Lake City, Utah, United States, 84108 | |
Contact: Carrie Bailey Carrie.Bailey@hsc.utah.edu | |
Principal Investigator: Nicola Longo, MD, PhD | |
United States, Virginia | |
Lysosomal & Rare Disorders Research & Treatment Center, Inc | Recruiting |
Fairfax, Virginia, United States, 22030 | |
Contact: Rekha Gopal 571-732-4606 rgopal@ldrtc.org | |
Principal Investigator: Ozlem Goker-Alpan, MD |
Study Director: | Raphael Schiffmann, MD, MHSc, FAAN | 4D Molecular Therapeutics |
Responsible Party: | 4D Molecular Therapeutics |
ClinicalTrials.gov Identifier: | NCT04519749 |
Other Study ID Numbers: |
4D-310-C001 |
First Posted: | August 20, 2020 Key Record Dates |
Last Update Posted: | April 4, 2022 |
Last Verified: | March 2022 |
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 |
Lysosomal Storage Diseases Nervous System Brain Diseases Inborn Brain Diseases Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Vascular Diseases Cardiovascular Diseases Genetic Diseases |
Metabolic Diseases Lipid Metabolism Disorders Metabolic X-Linked Inborn Sphingolipidoses Metabolism Inborn Errors Lipodoses Lipid Metabolism |
Fabry Disease Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Cerebral Small Vessel Diseases Cerebrovascular Disorders Vascular Diseases |
Cardiovascular Diseases Genetic Diseases, X-Linked Genetic Diseases, Inborn Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Sphingolipidoses Metabolism, Inborn Errors Lipidoses Lipid Metabolism, Inborn Errors |