VX-121 + Tezacaftor + Deutivacaftor for Cystic Fibrosis

Recruiting in Palo Alto (17 mi)

+35 other locations

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Transplantation, Cancer, Hepatic impairment, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests a combination of three drugs for cystic fibrosis patients with a specific genetic mutation. The drugs work together to fix the faulty protein in their cells, helping their lungs and other organs function better. Trikafta is a combination of three drugs (elexacaftor, tezacaftor, and ivacaftor) that target the F508del mutation in the CFTR gene.

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.

What data supports the effectiveness of the drug VX-121 + Tezacaftor + Deutivacaftor for cystic fibrosis?

Research shows that similar drugs like tezacaftor and ivacaftor, when used together, improve lung function in cystic fibrosis patients by targeting the root cause of the disease. Additionally, a combination of elexacaftor, tezacaftor, and ivacaftor has been shown to halt lung function decline, suggesting that VX-121 + Tezacaftor + Deutivacaftor may have similar benefits. ^{1 2 3 4 5}

What makes the drug VX-121/TEZ/D-IVA unique for cystic fibrosis?

The drug VX-121/TEZ/D-IVA is unique because it combines three CFTR modulators, including a novel component, deutivacaftor, which may enhance the effectiveness of existing treatments like tezacaftor and ivacaftor by targeting the underlying genetic defect in cystic fibrosis more comprehensively. ^{1 3 5 6 7}

Research Team

Eligibility Criteria

This trial is for children aged 1-11 with stable cystic fibrosis who have at least one mutation responsive to the treatment. It's not suitable for those with a history of organ transplant, cancer, significant liver disease, or certain lung infections that worsen breathing.

Inclusion Criteria

My cystic fibrosis is stable and I have at least one CFTR gene mutation.

Exclusion Criteria

My liver function is moderately impaired.

I have a history of organ transplant or cancer.

My liver is severely impaired.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants receive VX-121/TEZ/D-IVA in the morning to evaluate pharmacokinetics, safety, and tolerability

8 weeks

Treatment Part B

Participants receive VX-121/TEZ/D-IVA in the morning with doses based on Part A outcomes

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• VX-121/TEZ/D-IVA (CFTR Modulator)

Trial Overview The study tests VX-121/tezacaftor/deutivacaftor in young CF patients to see how their bodies handle it and if it's safe and effective. The medication aims to improve lung function by targeting the defective protein causing CF.

Participant Groups

Group I: Part B: VX-121/TEZ/D-IVA Experimental Treatment 1 Intervention

Participants will receive VX-121/TEZ/D-IVA in the morning with the dose(s) to be based on the outcome of Part A.

Group II: Part A: VX-121/TEZ/D-IVA Experimental Treatment 1 Intervention

Participants will receive VX-121/TEZ/D-IVA in the morning.

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

Findings from Research

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is safe and effective for people with cystic fibrosis who have at least one F508del-CFTR allele, showing significant improvements in lung function and quality of life in Phase 3 trials.

In a 2-year evaluation, participants treated with ELX/TEZ/IVA experienced no loss in lung function, while untreated individuals saw an average decline of 1.92 percentage points in lung function, marking ELX/TEZ/IVA as the first therapy to halt lung function decline in cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS. Lee, T., Sawicki, GS., Altenburg, J., et al.[2023]

CFTR modulators, like tezacaftor/ivacaftor, represent a significant advancement in treating cystic fibrosis by targeting the underlying genetic defect, with promising results from pivotal clinical trials.

Tezacaftor/ivacaftor has a better safety profile compared to lumacaftor/ivacaftor and is effective for a wider range of CFTR mutations, paving the way for future therapies that could benefit most cystic fibrosis patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezacaftor and ivacaftor for the treatment of cystic fibrosis. Paterson, SL., Barry, PJ., Horsley, AR.[2021]

References

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

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

EFFECT OF ELEXACAFTOR/TEZACAFTOR/IVACAFTOR ON ANNUAL RATE OF LUNG FUNCTION DECLINE IN PEOPLE WITH CYSTIC FIBROSIS. [2023]

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

Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Structural changes in lung morphology detected by MRI after modulating therapy with elexacaftor/tezacaftor/ivacaftor in adolescent and adult patients with cystic fibrosis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Tezacaftor and ivacaftor for the treatment of cystic fibrosis. [2021]

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

Acneiform Eruption Following Elexacaftor-Tezacaftor-Ivacaftor Treatment in Patients With Cystic Fibrosis. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Impact of lumacaftor/ivacaftor and tezacaftor/ivacaftor on treatment response in pulmonary exacerbations of F508del/F508del cystic fibrosis. [2023]