4D-710 in Adult Patients With Cystic Fibrosis (CF)

• ClinicalTrials.gov Identifier: NCT05248230
• Recruitment Status: Recruiting
• First Posted: February 21, 2022
• Last Update Posted: February 6, 2023
• Sponsor: 4D Molecular Therapeutics
• Information provided by (Responsible Party): 4D Molecular Therapeutics

Tracking Information

• First Submitted Date: February 10, 2022
• First Posted Date: February 21, 2022
• Last Update Posted Date: February 6, 2023
• Actual Study Start Date: March 29, 2022
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 7, 2022)

Incidence and severity of adverse events [ Time Frame: 24 Months ]

Safety and tolerability of 4D-710 following a single inhalation 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.

Original Primary Outcome Measures (submitted: February 10, 2022)

Primary Outcome Measure [ Time Frame: 24 Months ]

Incidence and severity of treatment emergent AEs (TEAEs), serious adverse events (SAEs), and dose limiting toxicities (DLTs).

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 4D-710 in Adult Patients With Cystic Fibrosis
• Official Title: An Open-label, Phase 1/2 Trial of Gene Therapy 4D-710 in Adults With Cystic Fibrosis
• Brief 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.
• Detailed Description: This Phase 1/2 trial will evaluate the safety, tolerability, and preliminary efficacy of 2 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis Lung

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 (CFTRΔR).

Study Arms

• Experimental: 4D-710 Dose Exploration Cohort 1
  Single inhalational administration of 4D-710 Dose Level 1
  Intervention: Biological: 4D-710
• Experimental: 4D-710 Dose Exploration Cohort 2
  Single inhalational administration of 4D-710 Dose Level 2
  Intervention: Biological: 4D-710
• Experimental: 4D-710 Dose Expansion Cohort
  Single inhalational administration of 4D-710 at the selected dose
  Intervention: Biological: 4D-710

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 10, 2022): 21
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2025
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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
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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: 4DMT Patient Advocacy; (888) 748-8881; clinicaltrials@4DMT.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05248230
• Other Study ID Numbers: 4D-710-C001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: 4D Molecular Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: 4D Molecular Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Susan Limb, MD; 4D Molecular Therapeutics

• PRS Account: 4D Molecular Therapeutics
• Verification Date: February 2023