VX-522 mRNA Therapy for Cystic Fibrosis

Recruiting at 44 trial locations

Overseen By Medical Information

Age: 18 - 65

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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing VX-522, a new treatment for adults with cystic fibrosis who don't respond to current treatments. The treatment aims to fix or improve the faulty gene causing the disease, potentially reducing symptoms and improving health.

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.

How is the drug VX-522 different from other cystic fibrosis treatments?

VX-522 is an mRNA therapy, which is a novel approach that uses messenger RNA to instruct cells to produce the correct form of the CFTR protein, potentially addressing the root cause of cystic fibrosis, unlike existing treatments that mainly focus on managing symptoms or enhancing the function of defective CFTR proteins. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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) Arm 1: VX-522 Experimental Treatment 1 Intervention

Participants grouped into different cohorts will receive multiple ascending doses of VX-522 in treatment arm 1 (T1).

Group III: MAD Arm 2: VX522+ IVA Experimental Treatment 2 Interventions

Following run-in period with ivacaftor (IVA), participants grouped into different cohorts will receive multiple ascending doses of VX-522 with IVA in treatment arm (T2).

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+

Findings from Research

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 (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]

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]

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, 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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Ivacaftor: the first therapy acting on the primary cause of cystic fibrosis. [2017]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Combined effects of VX-770 and VX-809 on several functional abnormalities of F508del-CFTR channels. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. [2023]