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

4D Molecular Therapeutics (4DMT)

Status and phase: Enrolling; Phase 2

Conditions: Cystic Fibrosis Lung

Treatments: Biological: 4D-710

Study type: Interventional

Funder types: Industry

Identifiers

NCT05248230

4D-710-C001

Details and patient eligibility

About

This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with cystic fibrosis.

Full description

This Phase 1/2 trial will evaluate the safety, tolerability, and preliminary efficacy of 4D-710, an investigational gene therapy, in adults with cystic fibrosis (CF) advanced lung disease who are ineligible or unable to tolerate CFTR modulator therapy. A sub-study will evaluate 4D-710 in a cohort of adults with CF advanced lung disease and/or frequent pulmonary exacerbation (PE) while on currently available CFTR modulator therapy.

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 (elexacaftor/tezacaftor/ivacaftor) for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 12-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 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. Contraindication to systemic corticosteroid therapy

5. Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition

6. If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening

7. If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C > 7.5% at Screening

8. Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment

9. Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia

10. Body Mass Index (BMI) < 16

11. Laboratory abnormalities at screening:

    • ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
    • Total bilirubin ≥ 2 × ULN
    • Hemoglobin < 10 g/dL

12. Requirement for continuous or night-time oxygen supplementation

13. Known CF liver disease with evidence of multilobular cirrhosis

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

40 participants in 3 patient groups

4D-710 Phase 1: Dose Exploration

Experimental group

Description:

Participants who are ineligible for or intolerant of modulator therapy will receive one of various dose levels of 4D-710 to identify recommended phase 2 dose(s) for further evaluation.

Treatment:

Biological: 4D-710

4D-710 Phase 2: Dose Expansion

Experimental group

Description:

Participants will receive a single inhalational administration of 4D-710 at the dose level(s) selected for dose expansion.

Treatment:

Biological: 4D-710

4D-710 Dose Exploration (Sub-Study)

Experimental group

Description:

Participants who are on currently available CFTR modulator therapy will receive a dose of 4D-710 at various dose levels.

Treatment:

Biological: 4D-710