Clinical trial NCT05248230: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cystic Fibrosis Lung
Keywords: CF
Cystic Fibrosis
Gene Therapy
Lead sponsor: 4D Molecular Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-02-21
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Incidence and severity of adverse events
timeFrame: 24 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Child Health Research Unit
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Health
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: 4D Molecular Therapeutics
name: Alan H. Cohen, MD
role: STUDY_DIRECTOR
References: