VX-121 + Tezacaftor + Deutivacaftor for Cystic Fibrosis

Recruiting at 39 trial locations

Overseen By Medical Information

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Transplantation, Cancer, Hepatic impairment, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

210 Participants Needed

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}

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.

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

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

Tezacaftor, when used in combination with ivacaftor, significantly improved CFTR function in cystic fibrosis patients, leading to a notable decrease in sweat chloride levels and an increase in lung function (ppFEV1) after 28 days of treatment.

The study, which involved a randomized, placebo-controlled design with subjects homozygous for F508del and compound heterozygous for F508del and G551D, showed that the combination therapy was safe, with adverse events similar across treatment groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR. Donaldson, SH., Pilewski, JM., Griese, M., et al.[2019]

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]

In a phase 3 trial involving 510 patients with cystic fibrosis, the combination of tezacaftor and ivacaftor significantly improved lung function, with an absolute increase in FEV1 of 4.0 percentage points compared to placebo (P<0.001).

The treatment also reduced the rate of pulmonary exacerbations by 35% compared to placebo, while showing a similar incidence of adverse events, indicating that it is both effective and safe for patients aged 12 and older with the CFTR Phe508del mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. Taylor-Cousar, JL., Munck, A., McKone, EF., et al.[2018]

In a study of 19 cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) for 6 months, significant improvements were observed in lung structure, including reduced bronchial wall thickening and mucus plugging, as assessed by MRI.

Patients also showed marked clinical benefits, including improved respiratory function (FEV1% increased from 58.5% to 71.4%), better body mass index, and reduced pulmonary exacerbations, confirming the efficacy of ELX/TEZ/IVA in managing cystic fibrosis.

NCBI (Pubmed)

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. Fainardi, V., Skenderaj, K., Ciuni, A., 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]

In a study of 16 cystic fibrosis patients treated with the combination therapy of elexacaftor, tezacaftor, and ivacaftor (ELX-TEZ-IVA), 37.5% developed new acneiform rashes, while 62.5% experienced a relapse or worsening of previous acne, indicating a notable skin-related side effect of this treatment.

Despite the occurrence of acneiform eruptions, most cases were mild and manageable with treatments like topical medications and isotretinoin, leading to partial or complete remission in 85.7% of patients reevaluated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acneiform Eruption Following Elexacaftor-Tezacaftor-Ivacaftor Treatment in Patients With Cystic Fibrosis. Okroglic, L., Sohier, P., Martin, C., et al.[2023]

In a study involving 982 pulmonary exacerbation events in cystic fibrosis patients, those receiving CFTR modulators lumacaftor/ivacaftor or tezacaftor/ivacaftor did not show greater improvements in lung function or other clinical measures after antibiotic treatment compared to those not on these medications.

This suggests that while CFTR modulators reduce the frequency of pulmonary exacerbations, they do not enhance the immediate clinical response to acute treatment during exacerbations in patients with the F508del mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of lumacaftor/ivacaftor and tezacaftor/ivacaftor on treatment response in pulmonary exacerbations of F508del/F508del cystic fibrosis. McElvaney, OJ., Heltshe, SL., Odem-Davis, K., et al.[2023]

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]