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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05629559




Registration number
NCT05629559
Ethics application status
Date submitted
4/11/2022
Date registered
29/11/2022
Date last updated
8/04/2024

Titles & IDs
Public title
4D-310 in Adults With Fabry Disease and Cardiac Involvement
Scientific title
An Open-Label, Phase 1/2a Trial of Gene Therapy 4D-310 in Adults With Fabry Disease and Cardiac Involvement
Secondary ID [1] 0 0
4D-310-C002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 4D-310
Treatment: Other - 4D-310
Treatment: Other - 4D-310

Experimental: 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A - 4D-310 Dose Level 1 - AAV NAb Titer Group A patients

Experimental: 4D-310 Dose Level 1 - AAV NAb Titer Group B - 4D-310 Dose Level 1 - AAV NAb titer Group B patients

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

Experimental: 4D-310 Dose Expansion - Dose expansion cohort of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients


Treatment: Other: 4D-310
Single IV administration of 4D-310 Dose Level 1

Treatment: Other: 4D-310
Single IV administration of 4D-310 Dose Level 2

Treatment: Other: 4D-310
Single IV administration of 4D-310 at the selected dose
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of adverse events
Timepoint [1] 0 0
1 year
Secondary outcome [1] 0 0
Change from baseline in serum AGA activity
Timepoint [1] 0 0
1 year
Secondary outcome [2] 0 0
Change from baseline serum globotriaosylsphingosine (lysoGb3)
Timepoint [2] 0 0
1 year

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2030
Actual
Sample size
Target
18
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
3050 - Melbourne
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
Taiwan
State/province [1] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
4D Molecular Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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 and cardiac involvement
Trial website
https://clinicaltrials.gov/study/NCT05629559
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alan H Cohen, MD
Address 0 0
4D Molecular Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05629559