Clinical trial NCT04519749: An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
Official title: An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Fabry Disease
Keywords: 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
Inborn
Metabolic Diseases
Lipid Metabolism Disorders
Sphingolipidoses
Metabolism
Inborn Errors
Lipidoses
Lipid Metabolism
Lead sponsor: 4D Molecular Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-08-20
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 1 year
Secondary outcomes:
measure: Change from baseline in serum AGA activity
timeFrame: 1 year
measure: Change from baseline serum globotriaosylsphingosine (lysoGb3)
timeFrame: 1 year
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California at San Diego
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal & Rare Disorders Research & Treatment Center, Inc
state: Virginia
Study officials:
affiliation: 4D Molecular Therapeutics
name: Alan H Cohen, MD
role: STUDY_DIRECTOR
References: