4D-710 in Adult Patients With Cystic Fibrosis

Cystic Fibrosis Lung Clinical Trial

— CF  

Official title:

An Open-label, Phase 1/2 Trial of Gene Therapy 4D-710 in Adults With Cystic Fibrosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05248230
• Other study ID #: 4D-710-C001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 29, 2022
• Est. completion date: January 2027

Study information

• Verified date: December 2023
• Source: 4D Molecular Therapeutics
• Contact: 4DMT Patient Advocacy
• Phone: (888) 748-8881
• Email: clinicaltrials[@]4DMT.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with CF who are ineligible for or unable to tolerate CFTR modulator therapy.

Description:

This Phase 1/2 trial will evaluate the safety, tolerability, and preliminary efficacy of 4 dose levels of 4D-710, an investigational gene therapy, in adults with cystic fibrosis lung disease who are ineligible or unable to tolerate CFTR modulator therapy.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: January 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

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 =100% of predicted (per Global Lung Function Initiative) at Screening

4. Resting oxygen saturation = 92% on room air at Screening

Key Exclusion Criteria:

1. Any prior gene therapy for any indication (Exception: mRNA-based 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. Two or more pulmonary exacerbations requiring treatment with intravenous (IV) antibiotics within 6 months prior to Screening

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 cirrhosis

15. History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis Lung
• Fibrosis
• Pulmonary Fibrosis

Intervention

Biological:
• 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 (CFTR?R).

Locations

Country	Name	City	State
United States	University of Alabama Child Health Research Unit	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Penn State Health	Hershey	Pennsylvania
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	The Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	University of Washington Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
4D Molecular Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events	Safety and tolerability of 4D-710 following a single inhalation dose, 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.	24 Months