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

January 4, 2024 updated by: 4D Molecular Therapeutics

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama Child Health Research Unit
        • Contact:
        • Contact:
        • Principal Investigator:
          • George M. Solomon, MD
    • Colorado
      • Denver, Colorado, United States, 80206
    • Illinois
      • Chicago, Illinois, United States, 60611
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Medical Center
        • Contact:
        • Principal Investigator:
          • Joel Mermis, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Allen Lapey, MD
        • Contact:
    • North Carolina
    • Ohio
      • Cleveland, Ohio, United States, 44146
      • Columbus, Ohio, United States, 43205
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
      • Philadelphia, Pennsylvania, United States, 19104
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • The University of Texas Southwestern Medical Center
        • Contact:
        • Principal Investigator:
          • Raksha Jain, MD
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University Health System
        • Contact:
        • Principal Investigator:
          • Nauman A. Chaudary, MD
    • Washington
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington Medical Center
        • Principal Investigator:
          • Christopher Goss, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  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 ≤100% of predicted (per Global Lung Function Initiative) at Screening
  4. Resting oxygen saturation ≥ 92% on room air at Screening

Key Exclusion Criteria:

  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. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 4D-710 Dose Expansion Cohort
Single inhalational administration of 4D-710 at the selected dose
Biological: 4D-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).
Experimental: 4D-710 Dose Exploration Cohort 1
Single inhalational administration of 4D-710 Dose 1
Biological: 4D-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).
Experimental: 4D-710 Dose Exploration Cohort 2
Single inhalational administration of 4D-710 Dose 2
Biological: 4D-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).
Experimental: 4D-710 Dose Exploration Cohort 3
Single inhalational administration of 4D-710 Dose 3
Biological: 4D-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).
Experimental: 4D-710 Dose Exploration Cohort 4
Single inhalational administration of 4D-710 Dose 4
Biological: 4D-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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events
Time Frame: 24 Months
Safety and tolerability of 4D-710 following a single inhalation dose, as assessed by incidence and severity of treatment emergent adverse events, serious adverse events, and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters.
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

4D Molecular Therapeutics

Investigators

  • Study Director: Alan H. Cohen, MD, 4D Molecular Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2022

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

February 10, 2022

First Submitted That Met QC Criteria

February 10, 2022

First Posted (Actual)

February 21, 2022

Study Record Updates

Last Update Posted (Estimated)

January 8, 2024

Last Update Submitted That Met QC Criteria

January 4, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4D-710-C001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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