4D-710 in Adult Patients With Cystic Fibrosis
Purpose
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.
Condition
- Cystic Fibrosis Lung
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
Exclusion Criteria
- 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
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Sequential Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 4D-710 Dose Exploration Cohort 1 |
Single inhalational administration of 4D-710 Dose 1 |
|
|
Experimental 4D-710 Dose Exploration Cohort 2 |
Single inhalational administration of 4D-710 Dose 2 |
|
|
Experimental 4D-710 Dose Exploration Cohort 3 |
Single inhalational administration of 4D-710 Dose 3 |
|
|
Experimental 4D-710 Dose Exploration Cohort 4 |
Single inhalational administration of 4D-710 Dose 4 |
|
|
Experimental 4D-710 Dose Expansion Cohort |
Single inhalational administration of 4D-710 at the selected dose |
|
Recruiting Locations
University of Kansas Medical Center
Kansas City, Kansas 66160
Kansas City, Kansas 66160
More Details
- Status
- Recruiting
- Sponsor
- 4D Molecular Therapeutics
Detailed 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.