What is the mechanism of action of this treatment?

The most common treatments for Cystic Fibrosis (CF) include CFTR modulators and gene therapy. CFTR modulators, such as elexacaftor-tezacaftor-ivacaftor, enhance the function of the defective CFTR protein, which is essential for regulating salt and water movement in and out of cells, thereby reducing the thick mucus that clogs airways. Gene therapy, like the investigational 4D-710, delivers a functional CFTR gene to the patient's cells to compensate for the defective gene, potentially addressing the root cause of CF. These treatments are crucial for CF patients as they target the underlying genetic defect, potentially improving lung function, reducing infections, and enhancing overall quality of life.

What side effects are associated with this type of intervention?

Gene therapy for cystic fibrosis, such as the investigational 4D-710, aims to deliver a functional CFTR gene to compensate for the defective one. Known side effects of gene therapy can include immune reactions to the viral vector used for gene delivery, which may cause inflammation or other immune responses. Other common treatments for CF, such as inhaled antibiotics (e.g., tobramycin, aztreonam) and CFTR modulators (e.g., elexacaftor-tezacaftor-ivacaftor), can cause side effects like bronchial constriction, gastrointestinal issues, liver enzyme elevations, and respiratory symptoms. It is important for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several CFTR modulators for the treatment of Cystic Fibrosis, which work by improving the function of the defective CFTR protein. Notable drugs include ivacaftor, lumacaftor/ivacaftor, tezacaftor/ivacaftor, and the triple combination elexacaftor/tezacaftor/ivacaftor. These treatments are designed to enhance the activity of the CFTR protein in patients with specific genetic mutations. While gene therapy approaches like 4D-710, which aim to deliver a functional CFTR gene to compensate for the defective one, are still under investigation, they represent a promising future direction for CF treatment.

What other types of research exist?

Promising alternatives to 4D-710 for cystic fibrosis patients include: 1) CFTR modulators such as Trikafta (elexacaftor/tezacaftor/ivacaftor), which have shown significant improvements in lung function and quality of life. 2) Inhaled antibiotics like tobramycin and aztreonam for chronic Pseudomonas aeruginosa infections, which help manage pulmonary infections. 3) Anti-inflammatory treatments such as high-dose ibuprofen and azithromycin, which reduce lung inflammation and slow disease progression. 4) Other gene therapies under investigation, including those by the UK CF Gene Therapy Consortium, which focus on improving CFTR function through different vectors and delivery methods.

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Gene Therapy

Gene Therapy (4D-710) for Cystic Fibrosis (CF Trial)

Phase 1 & 2

Recruiting

Research Sponsored by 4D Molecular Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Mutation Status: Bi-allelic mutations in the CFTR gene, or Single mutation in the CFTR gene and clinical manifestations of CF lung disease

18 years and older

Must not have

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 cirrhosis, History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis

Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new gene therapy called 4D-710 in adults with cystic fibrosis who can't use standard treatments. The goal is to see if it is safe and effective. 4D-710 is part of a new generation of AAV vectors being developed for cystic fibrosis gene therapy.

Who is the study for?

Adults with cystic fibrosis who can't take CFTR modulator therapy or had bad reactions to it. They must be 18+, have certain genetic mutations, and their lung function should be within a specific range. People with recent serious infections, liver disease, diabetes not well controlled, or those on chronic steroids/immunosuppressants can't join.

What is being tested?

The trial is testing a single dose of an investigational gene therapy called 4D-710 in adults with cystic fibrosis. It's an early-stage study (Phase 1/2) to see how safe the treatment is and how the body responds to it.

What are the potential side effects?

Since this is an early-phase trial for gene therapy, exact side effects are unknown but may include immune reactions, changes in blood tests like liver enzymes, potential for new allergies or worsening of existing ones due to genetic modification.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have either two mutations in the CFTR gene or one mutation with CF lung symptoms.

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I am 18 years old or older.

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I can't take CFTR modulator therapy or stopped it due to side effects.

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I have been diagnosed with cystic fibrosis and lung disease related to CF.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am being treated for a severe lung allergy with steroids or antifungal medication.

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I am currently being treated for an active Mycobacterium abscessus infection.

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My last A1C level was above 7.5%.

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My A1C level is 6.5% or higher and I don't have a known diabetes diagnosis.

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I've needed IV antibiotics for lung issues at least twice in the last 6 months.

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I cannot take systemic corticosteroids due to health reasons.

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I regularly take steroids or immunosuppressants for another condition.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence and severity of adverse events

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Group I: 4D-710 Phase 2: Dose ExpansionExperimental Treatment1 Intervention

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

Group II: 4D-710 Phase 1: Dose ExplorationExperimental Treatment1 Intervention

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 III: 4D-710 Dose Exploration (Sub-Study)Experimental Treatment1 Intervention

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

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Cystic Fibrosis (CF) include CFTR modulators and gene therapy. CFTR modulators, such as elexacaftor-tezacaftor-ivacaftor, enhance the function of the defective CFTR protein, which is essential for regulating salt and water movement in and out of cells, thereby reducing the thick mucus that clogs airways. Gene therapy, like the investigational 4D-710, delivers a functional CFTR gene to the patient's cells to compensate for the defective gene, potentially addressing the root cause of CF. These treatments are crucial for CF patients as they target the underlying genetic defect, potentially improving lung function, reducing infections, and enhancing overall quality of life.

Gene therapy for cystic fibrosis using E1-deleted adenovirus: a phase I trial in the nasal cavity. The University of North Carolina at Chapel Hill.[Cystic fibrosis].Novel therapeutic approaches for the management of cystic fibrosis.