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

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.

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.

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).

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.

Key Inclusion Criteria: 18 years and older Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including: Sweat chloride ≥ 60 mmol/L Mutation Status Bi-allelic mutations in the CFTR gene, or Single mutation in the CFTR gene and clinical manifestations of CF lung disease Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects. Forced expiratory volume in 1 second (FEV1) ≥50% and ≤100% of predicted (per Global Lung Function Initiative) at Screening Resting oxygen saturation ≥ 92% on room air at Screening Key Exclusion Criteria: Any prior gene therapy for any indication Active Mycobacterium abscessus infection requiring ongoing treatment at Screening Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy Two or more pulmonary exacerbations requiring treatment with intravenous (IV) antibiotics within 6 months prior to Screening Contraindication to systemic corticosteroid therapy Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥6.5% at Screening If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C >7.5% at Screening Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia Body Mass Index (BMI) <16 Laboratory abnormalities at screening: ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN) Total bilirubin ≥ 2 × ULN Hemoglobin < 10 g/dL Requirement for continuous or night-time oxygen supplementation Known CF liver disease with evidence of cirrhosis History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis