Fabry DiseasePhase 1/2NCT04519749
An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
A Phase 1/2 study testing 4D-310 in people with Fabry Disease, run by 4D Molecular Therapeutics at 4 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- 4D-310
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Sep 2020to Jun 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥ 18 years of age
- Pathogenic GLA mutation consistent with Fabry Disease
- Confirmed diagnosis of classic or late-onset Fabry disease
- 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
- Agree to use highly effective contraception
Who cannot join
- Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
- eGFR <45 mL/min/1.73 m2
- Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
- HIV, active or chronic hepatitis B or C,
- Evidence of liver disease, severe pulmonary disease or 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)
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- 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 or 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)
- Pregnant or breast-feeding
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30322
Lysosomal & Rare Disorders Research & Treatment Center, Inc
Fairfax, Virginia, 22030
University of California at San Diego
La Jolla, California, 92037
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224
About this study
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.
Read the 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.
- Conditions
- Fabry Disease
- Being tested
- 4D-310
- 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
- Medical subject headings
- Fabry Disease, Lysosomal Storage Diseases, Brain Diseases, Metabolic, Central Nervous System Diseases, Nervous System Diseases, Cerebral Small Vessel Diseases, Cerebrovascular Disorders, Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4D-310Biological
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).
| Study group | Role | What they receive |
|---|---|---|
| 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A | Experimental | Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients Receives: Biological: 4D-310 |
| 4D-310 Dose Level 1 - AAV NAb Titer Group B | Experimental | Single IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients Receives: Biological: 4D-310 |
| 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B | Experimental | Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients Receives: Biological: 4D-310 |
| 4D-310 Dose Expansion | Experimental | Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients Receives: Biological: 4D-310 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and severity of adverse events
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
Measured: 1 year
Secondary outcomes (2)
Change from baseline in serum AGA activity
Change from baseline in serum AGA activity
Measured: 1 year
Change from baseline serum globotriaosylsphingosine (lysoGb3)
Change from baseline serum globotriaosylsphingosine (lysoGb3)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start1 Sep 2020
- Primary completionJan 2026 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- More trials run by 4D Molecular TherapeuticsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 4D Molecular Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan H Cohen, MD, Study director, 4D Molecular Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04519749
- Sponsor's protocol ID
- 4D-310-C001
- Status last verified
- Apr 2024
- First submitted
- 14 Aug 2020
- Last updated
- 8 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase 1/2 Trial of Gene Therapy 4D-310 in Adults With Fabry Disease
- ClinicalTrials.gov ID
- NCT04519749
- Acronym / sponsor ID
- 4D-310-C001
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- 4D Molecular TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- Jan 2026 (estimated)
- Study completion
- Jun 2030 (estimated)
- First posted
- 20 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A | Experimental | Biological: 4D-310Single IV administration of 4D-310 Dose Level 1 - AAV NAb Titer Group A patients |
| 4D-310 Dose Level 1 - AAV NAb Titer Group B | Experimental | Biological: 4D-310Single IV administration of 4D-310 Dose Level 1 - AAV NAb titer Group B patients |
| 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B | Experimental | Biological: 4D-310Single IV administration of 4D-310 at Dose Level 2 in AAV NAb titer Group A and/or B patients |
| 4D-310 Dose Expansion | Experimental | Biological: 4D-310Dose expansion cohort of single IV administration of 4D-310 at the selected dose and selected AAV Nab titer group(s) patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female ≥ 18 years of age
- Pathogenic GLA mutation consistent with Fabry Disease
- Confirmed diagnosis of classic or late-onset Fabry disease
- 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
- Agree to use highly effective contraception
Key exclusion criteria (14 listed)
- Presence of high titer neutralizing antibody to 4D-310 capsid, or presence of high antibody titer to AGA
- eGFR <45 mL/min/1.73 m2
- Undergone kidney transplantation or currently on hemodialysis or peritoneal dialysis
- HIV, active or chronic hepatitis B or C,
- Evidence of liver disease, severe pulmonary disease or diabetes with poor glycemic control
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4D-3104D-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). | Biological | 4D-310 Dose Expansion, 4D-310 Dose Level 1 - AAV NAb Titer Group B, 4D-310 Dose Level 1 - AAV Neutralizing Antibody (NAb) Group A, 4D-310 Dose Level 2 - AAV NAb Titer Group A and/or B |
Primary outcome
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
2 secondary outcomes
Change from baseline in serum AGA activity
Time frame: 1 year
Change from baseline serum globotriaosylsphingosine (lysoGb3)
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alan H Cohen, MD study director
4D Molecular Therapeutics
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 4D-310 in people with Fabry Disease, run by 4D Molecular Therapeutics at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and severity of adverse events (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2024.