4D-710 in Adult Patients With Cystic Fibrosis

NCT ID: NCT05248230

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-29

Study Completion Date

2030-01-31

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 cystic fibrosis.

Detailed Description

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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.

Conditions

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Cystic Fibrosis Lung

Keywords

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CF Cystic Fibrosis Gene Therapy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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4D-710 Phase 1: Dose Exploration

Participants who are ineligible for or intolerant of modulator therapy will receive one of various dose levels of 4D-710 to identify recommended phase 2 dose(s) for further evaluation.

Group Type EXPERIMENTAL

4D-710

Intervention Type BIOLOGICAL

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).

4D-710 Phase 2: Dose Expansion

Participants will receive a single inhalational administration of 4D-710 at the dose level(s) selected for dose expansion.

Group Type EXPERIMENTAL

4D-710

Intervention Type BIOLOGICAL

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).

4D-710 Dose Exploration (Sub-Study)

Participants who are on currently available CFTR modulator therapy will receive a dose of 4D-710 at various dose levels.

Group Type EXPERIMENTAL

4D-710

Intervention Type BIOLOGICAL

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).

Interventions

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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).

Intervention Type BIOLOGICAL

Eligibility Criteria

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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 ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
4. Resting oxygen saturation ≥ 92% on room air at Screening


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

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. 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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4D Molecular Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alan H. Cohen, MD

Role: STUDY_DIRECTOR

4D Molecular Therapeutics

Locations

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University of Alabama Child Health Research Unit

Birmingham, Alabama, United States

Site Status RECRUITING

The University of Arizona

Tucson, Arizona, United States

Site Status RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

National Jewish Health

Denver, Colorado, United States

Site Status RECRUITING

University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

University of Miami Hospital

Miami, Florida, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status ACTIVE_NOT_RECRUITING

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

Cleveland, Ohio, United States

Site Status RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status RECRUITING

Penn State Health

Hershey, Pennsylvania, United States

Site Status RECRUITING

The Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

The University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Virginia Commonwealth University Health System

Richmond, Virginia, United States

Site Status RECRUITING

University of Washington Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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4DMT Patient Advocacy

Role: CONTACT

Phone: (888) 748-8881

Email: [email protected]

Facility Contacts

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Justin Anderson

Role: primary

Elizabeth Ryan

Role: primary

Legna Betancourt

Role: primary

Jennifer Taylor-Cousar, MD

Role: primary

Michele Gaffigan

Role: backup

Chrystal Bailey

Role: primary

Ivan Whitaker

Role: primary

Rachel Nelson

Role: primary

Lawrence Scott

Role: primary

Kaia Houtman

Role: primary

Margot Hardcastle

Role: primary

Monica Ulles

Role: primary

Tia Rone

Role: primary

Terri Johnson

Role: primary

Diane Kitch

Role: primary

Melissa Molter

Role: primary

Maria McLeod

Role: primary

Margaret K. Lessard

Role: primary

Roshni Prabhu

Role: primary

References

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Calton MA, Croze RH, Sullivan TH, Collins SA, Tucker S, Whittlesey KJ, Kim DH, Nye JA, Beliakoff G, Quezada M, Burns C, Schmitt C, Klein A, Jia V, Kovacs L, Lauko D, Yoh K, Nguyen K, Barglow K, Gonzales J, Khoday D, Mason T, Delaria K, Bashour K, Kotterman M, Schaffer D, Song A, Francis P, Taylor-Cousar JL, Kirn D. Design and Characterization of 4D-710, an Aerosolized Gene Therapy for Cystic Fibrosis Lung Disease. Am J Respir Cell Mol Biol. 2025 Oct 22. doi: 10.1165/rcmb.2025-0243MA. Online ahead of print.

Reference Type DERIVED
PMID: 41124321 (View on PubMed)

Other Identifiers

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4D-710-C001

Identifier Type: -

Identifier Source: org_study_id