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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05248230
Recruitment Status : Recruiting
First Posted : February 21, 2022
Last Update Posted : June 23, 2022
Sponsor:
Information provided by (Responsible Party):
4D Molecular Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Lung Biological: 4D-710 Phase 1 Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Phase 1/2 Trial of Gene Therapy 4D-710 in Adults With Cystic Fibrosis
Actual Study Start Date : March 29, 2022
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 4D-710 Dose Exploration Cohort 1
Single inhalational administration of 4D-710 Dose Level 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 Level 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 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).




Primary Outcome Measures :
  1. 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 adverse events, serious adverse events and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. 18 years and older
  2. Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:

    • Bi-allelic mutations in the CFTR gene, and
    • 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
  2. History of positive culture for Burkholderia cenocepacia, B. dolosa, or Mycobacterium abscessus within the past 24 months
  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 normal 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 cirrhosis
  14. Diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes
  15. History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05248230


Contacts
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Contact: 4DMT Patient Advocacy (888) 748-8881 clinicaltrials@4DMT.com

Locations
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United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Lawrence Scott       lscott2@kumc.edu   
Principal Investigator: Joel Mermis, MD         
United States, Massachusetts
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Monica Ulles       monica.ulles@childrens.harvard.edu   
Principal Investigator: Henry Dorkin, MD         
United States, Ohio
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center Recruiting
Cleveland, Ohio, United States, 44146
Contact: Laura Batke       Laura.Batke@UHhospitals.org   
Contact: Kathleen Hilliard       kathleen.hilliard@uhhospitals.org   
Principal Investigator: Alex Gifford, MD         
United States, Pennsylvania
The Hospital of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Melissa Molter       melissa.molter@pennmedicine.upenn.edu   
Principal Investigator: Daniel Dorgan, MD         
Sponsors and Collaborators
4D Molecular Therapeutics
Investigators
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Study Director: Susan Limb, MD 4D Molecular Therapeutics
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Responsible Party: 4D Molecular Therapeutics
ClinicalTrials.gov Identifier: NCT05248230    
Other Study ID Numbers: 4D-710-C001
First Posted: February 21, 2022    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by 4D Molecular Therapeutics:
CF
Cystic Fibrosis
Gene Therapy
Additional relevant MeSH terms:
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Cystic Fibrosis
Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases