VX-522 mRNA Therapy for Cystic Fibrosis

Recruiting at 78 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Uncontrolled asthma, Transplantation, Hepatic impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called VX-522, an mRNA therapy, for individuals with cystic fibrosis who don't respond to current CFTR modulator therapies. The study aims to determine if VX-522 is safe, tolerable, and effective in improving health conditions. Participants will receive varying doses of VX-522, sometimes combined with another medication called ivacaftor, to compare results. Ideal candidates have cystic fibrosis mutations that don’t produce the necessary protein, have stable disease, and don't have severe asthma or liver issues. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that VX-522 is a new mRNA therapy aimed at helping people with cystic fibrosis. Researchers are currently testing this treatment to determine its safety and tolerability. Early results indicate that adults with cystic fibrosis have received VX-522 in both single and multiple doses. The goal of these studies is to ensure the treatment does not cause serious side effects.

The trials also test VX-522 in combination with ivacaftor, a drug already used to treat cystic fibrosis, to ensure their combined safety.

Although detailed safety data from these studies is not yet available, the advanced stages of the trials suggest that earlier tests did not reveal major safety issues. This likely indicates the treatment was tolerated well enough to continue testing. However, more information from ongoing studies is needed to confirm its safety for broader use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about VX-522 mRNA therapy for cystic fibrosis because it offers a novel approach by using messenger RNA to address the underlying cause of the disease. Unlike current treatments like CFTR modulators, which enhance the function of the defective protein, VX-522 directly aims to provide cells with the instructions to produce the correct version of the CFTR protein themselves. Additionally, when combined with ivacaftor in some study arms, it could enhance the protein's function even further. This innovative mechanism has the potential to significantly improve lung function and overall quality of life for patients with cystic fibrosis.

What evidence suggests that VX-522 might be an effective treatment for cystic fibrosis?

Research has shown that VX-522 is a promising new treatment for cystic fibrosis (CF), particularly for those unresponsive to current treatments. VX-522 uses genetic material to help the body produce a protein missing in CF patients. Early results suggest this method could repair or improve the faulty protein in CF patients. In this trial, some participants will receive VX-522 alone, while others will receive it in combination with ivacaftor, a drug that enhances the function of certain proteins in CF. These early studies focus on assessing both the safety and potential effectiveness of this treatment in adults with a specific CF genetic makeup. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with cystic fibrosis who have specific CFTR gene mutations not treatable with current modulator therapies. Participants must have stable disease, a minimum lung function (FEV1 ≥40%), weigh over 50 kg, and have a BMI under 30. Excluded are those with low oxygen saturation (<94% on room air), uncontrolled asthma in the past year, any organ transplants, or moderate to severe liver issues.

Inclusion Criteria

Your cystic fibrosis (CF) is not getting worse.

Your lung function test results show that your breathing is less than 40% of what is expected for someone your age, sex, and height.

Your body mass index is less than 30.

Exclusion Criteria

Your blood oxygen level is less than 94% when breathing normal air.

Other protocol defined Inclusion/Exclusion criteria may apply.

You have had uncontrolled asthma in the past year before the screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple ascending doses of VX-522, with some cohorts also receiving ivacaftor (IVA)

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• VX-522

Trial Overview

The study tests VX-522 mRNA therapy's safety and how well participants tolerate it. It targets individuals aged 18+ whose cystic fibrosis results from certain CFTR gene mutations that don't respond to existing treatments.

How Is the Trial Designed?

Group I: Single Ascending Dose (SAD) Experimental Treatment 1 Intervention

Participants grouped into different cohorts will receive a single ascending dose of VX-522.

Group II: Multiple Ascending Dose (MAD) Cohort 1: VX-522 Experimental Treatment 1 Intervention

Participants will receive multiple ascending doses of VX-522.

Group III: MAD Cohort 2: VX-522+ IVA Experimental Treatment 2 Interventions

Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.

Group IV: MAD Cohort 1: VX-522+ IVA Experimental Treatment 2 Interventions

Following run-in period with ivacaftor (IVA), participants will receive multiple ascending doses of VX-522 with IVA.

Who Is Running the Clinical Trial?

Vertex Pharmaceuticals Incorporated

Lead Sponsor

Trials

267

Recruited

36,100+

Dr. David Altshuler

Vertex Pharmaceuticals Incorporated

Chief Medical Officer since 2020

MD, PhD

Dr. Reshma Kewalramani

Vertex Pharmaceuticals Incorporated

Chief Executive Officer since 2020

MD, trained in internal medicine and nephrology

Moderna, Inc

Collaborator

Trials

2

Recruited

50+

Published Research Related to This Trial

P. aeruginosa infection significantly reduces the effectiveness of the investigational drugs VX-809 and VX-770 in stimulating chloride secretion from F508del-CFTR in cystic fibrosis patients, which may explain the modest clinical efficacy observed in trials.

In laboratory studies using F508del-CFBE cells and primary cultures of CF-HBE cells, exposure to P. aeruginosa was shown to decrease both drug-stimulated chloride secretion and the abundance of F508del-CFTR on the cell surface, indicating a direct impact of the infection on treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. Stanton, BA., Coutermarsh, B., Barnaby, R., et al.[2019]

VX-770 (ivacaftor) is a promising drug that enhances the function of the CFTR protein, specifically targeting the G551D mutation, which is one of the most common mutations causing cystic fibrosis.

By improving CFTR chloride conductance, VX-770 has the potential to significantly enhance the clinical outcomes for cystic fibrosis patients, potentially improving their longevity and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ivacaftor: the first therapy acting on the primary cause of cystic fibrosis. McPhail, GL., Clancy, JP.[2017]

In a randomized trial of 52 children aged 6-11 with cystic fibrosis and a G551D-CFTR mutation, ivacaftor significantly improved lung function, as measured by FEV1, with a treatment effect of 12.5 percentage points compared to placebo over 48 weeks.

Patients taking ivacaftor also experienced greater weight gain (average of 2.8 kg more than placebo) and a significant reduction in sweat chloride levels, indicating improved CFTR activity, with no increase in adverse events compared to the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Davies, JC., Wainwright, CE., Canny, GJ., et al.[2022]

VX-770 effectively restores the opening rate of the F508del-CFTR channels, which are defective in cystic fibrosis, indicating its potential as a treatment for patients with this mutation.

VX-809 alone does not enhance the function of F508del-CFTR channels, but when combined with VX-770, it helps shift the channel equilibrium towards a more open state, improving channel activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels. Kopeikin, Z., Yuksek, Z., Yang, HY., et al.[2020]

VX-770, an oral CFTR potentiator, has been shown to significantly enhance the function of the CFTR protein in cells with common cystic fibrosis mutations, specifically increasing the channel's open probability and chloride secretion.

In cultured human bronchial epithelial cells from cystic fibrosis patients, VX-770 improved chloride secretion to about 50% of normal levels and helped prevent dehydration of the airway surface, indicating its potential to restore epithelial function in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Van Goor, F., Hadida, S., Grootenhuis, PD., et al.[2023]

Citations

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VX-522: A Promising New Treatment for Cystic Fibrosis

VX-522 is currently undergoing clinical trials to evaluate its safety and effectiveness in treating CF patients who haven't responded to other treatments.

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VX-522 mRNA Therapy for Cystic Fibrosis

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This study will evaluate the safety and tolerability of VX-522, an investigational inhaled messenger RNA (mRNA), in adults with CF whose mutations are not ...

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Novel, inhaled mRNA therapy intended for the

Vertex Announces Investigational New Drug (IND) Application for VX-522, mRNA Therapy for People With Cystic Fibrosis, Cleared by FDA · U.S. Food ...

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A Phase 1/2 Study of VX-522 in Subjects with Cystic Fibrosis

The BEACON-CF clinical research study will help to find out whether a single dose of an investigational study drug, called VX-522, is safe and well tolerated.