RecruitingPhase 2NCT05248230

4D-710 in Adult Patients With Cystic Fibrosis

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


Sponsor

4D Molecular Therapeutics

Enrollment

30 participants

Start Date

Mar 29, 2022

Study Type

INTERVENTIONAL

Conditions

Summary

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


Eligibility

Min Age: 18 Years

Inclusion Criteria17

  • 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 ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
  • Resting oxygen saturation ≥ 92% on room air at Screening
  • 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
  • Currently on a stable dose of CFTR modulator therapy for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 24-month Observation Period
  • 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

Exclusion Criteria18

  • Any prior gene therapy for any indication (Exception: mRNA-based or antisense oligonucleotide therapies are not exclusionary)
  • Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
  • Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
  • Smoking (e.g. cigarettes, cigars, cannabis) or use of a vaping product during the 2 months prior to screening; must agree to not smoke or use vaping products during Screening and initial 24-month observation period.
  • 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 multilobular cirrhosis
  • History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

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Interventions

BIOLOGICAL4D-710

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).


Locations(20)

University of Alabama Child Health Research Unit

Birmingham, Alabama, United States

The University of Arizona

Tucson, Arizona, United States

University of California San Francisco

San Francisco, California, United States

National Jewish Health

Denver, Colorado, United States

University of Florida

Gainesville, Florida, United States

University of Miami Hospital

Miami, Florida, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Penn State Health

Hershey, Pennsylvania, United States

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Virginia Commonwealth University Health System

Richmond, Virginia, United States

University of Washington Medical Center

Seattle, Washington, United States

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NCT05248230


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