Recruiting
Phase 2
4D-710 in Adult Patients With Cystic Fibrosis
Condition(s) studied
Cystic Fibrosis Lung
Investigational drug(s) / intervention(s)
4D-710
4D-710: 4D-710 is an adeno-associated virus (AAV) gene therapy comprised of an AAV capsid variant (4D-A101) carrying a transgene cassette encoding human cystic fibrosis transmembrane conductance regulator with a deletion in the regulatory domain (CFTRΔR).
Study summary
This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with cystic fibrosis.
Eligibility
Key Inclusion Criteria (Primary Study):
1. 18 years and older
2. Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
1. Sweat chloride ≥ 60 mmol/L
2. Mutation Status
* Bi-allelic mutations in the CFTR gene, or
* Single mutation in the CFTR gene and clinical manifestations of CF lung disease
3. Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
3. Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
4. Resting oxygen saturation ≥ 92% on room air at Screening
Key Inclusion Criteria (Sub-Study):
1. 18 years and older
2. Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
1. Sweat chloride ≥ 60 mmol/L
2. Mutation Status
* Bi-allelic mutations in the CFTR gene, or
* Single mutation in the CFTR gene and clinical manifestations of CF lung disease
3. Currently on a stable dose of CFTR modulator therapy for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 24-month Observation Period
4. FEV1 ≥ 40% and \< 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics
Key Exclusion Criteria (Primary and Sub Study):
1. Any prior gene therapy for any indication (Exception: mRNA-based or antisense oligonucleotide therapies are not exclusionary)
2. Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
3. Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
4. Smoking (e.g. cigarettes, cigars, cannabis) or use of a vaping product during the 2 months prior to screening; must agree to not smoke or use vaping products during Screening and initial 24-month observation period.
5. Contraindication to systemic corticosteroid therapy
6. Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
7. If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
8. If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C \> 7.5% at Screening
9. Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
10. Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
11. Body Mass Index (BMI) \< 16
12. Laboratory abnormalities at screening:
* ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
* Total bilirubin ≥ 2 × ULN
* Hemoglobin \< 10 g/dL
13. Requirement for continuous or night-time oxygen supplementation
14. Known CF liver disease with evidence of multilobular cirrhosis
15. History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis
Primary outcome measure(s)
- Incidence and severity of adverse events — 60 Months
Safety and tolerability of 4D-710 following a single dose via inhalation, as assessed by incidence and severity of treatment emergent adverse events, serious adverse events, and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters.
Trial sites (20)
| Facility | City | Region | Status |
| University of Alabama Child Health Research Unit |
Birmingham |
Alabama |
Recruiting |
| The University of Arizona |
Tucson |
Arizona |
Recruiting |
| University of California San Francisco |
San Francisco |
California |
Recruiting |
| National Jewish Health |
Denver |
Colorado |
Recruiting |
| University of Florida |
Gainesville |
Florida |
Recruiting |
| University of Miami Hospital |
Miami |
Florida |
Recruiting |
| Northwestern Memorial Hospital |
Chicago |
Illinois |
Recruiting |
| University of Kansas Medical Center |
Kansas City |
Kansas |
Recruiting |
| Johns Hopkins Hospital |
Baltimore |
Maryland |
Recruiting |
| Massachusetts General Hospital |
Boston |
Massachusetts |
Recruiting |
| Boston Children's Hospital |
Boston |
Massachusetts |
Recruiting |
| University of North Carolina at Chapel Hill |
Chapel Hill |
North Carolina |
Completed |
| Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center |
Cleveland |
Ohio |
Recruiting |
| Nationwide Children's Hospital |
Columbus |
Ohio |
Recruiting |
| Penn State Health |
Hershey |
Pennsylvania |
Withdrawn |
| The Hospital of the University of Pennsylvania |
Philadelphia |
Pennsylvania |
Recruiting |
| Medical University of South Carolina |
Charleston |
South Carolina |
Recruiting |
| The University of Texas Southwestern Medical Center |
Dallas |
Texas |
Recruiting |
| Virginia Commonwealth University Health System |
Richmond |
Virginia |
Recruiting |
| University of Washington Medical Center |
Seattle |
Washington |
Recruiting |
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