4D-710 in Adult Patients With Cystic Fibrosis

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Cystic Fibrosis Lung

Intervention / Treatment
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* Biological: 4D-710


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4D-710 Dose Exploration Cohort 1<br>Single inhalational administration of 4D-710 Dose Level 1 | Biological: 4D-710<br>* 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).<br>|
| Experimental: 4D-710 Dose Exploration Cohort 2<br>Single inhalational administration of 4D-710 Dose Level 2 | Biological: 4D-710<br>* 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).<br>|
| Experimental: 4D-710 Dose Expansion Cohort<br>Single inhalational administration of 4D-710 at the selected dose | Biological: 4D-710<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events | 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. | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CF, Cystic Fibrosis, Gene Therapy