VX-121 Combination Therapy for Cystic Fibrosis

Recruiting at 194 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Drug intolerance, Pregnancy, Breast-feeding, 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

822 Participants Needed

Trial Summary

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/TEZ/D-IVA for cystic fibrosis?

Research shows that similar combination treatments like tezacaftor and ivacaftor improve the function of the CFTR protein, which is often defective in cystic fibrosis patients. This suggests that VX-121/TEZ/D-IVA, which includes similar components, may also be effective in treating cystic fibrosis. ^{1 2 3 4 5}

Is VX-121 Combination Therapy for Cystic Fibrosis safe for humans?

The safety of similar combination therapies for cystic fibrosis, like elexacaftor-tezacaftor-ivacaftor, has been studied, showing common side effects such as rash and headache. Monitoring liver function is recommended, and ongoing evaluation is needed to confirm long-term safety. ^{1 2 6 7 8}

What is the purpose of this trial?

The purpose of this study is to evaluate the long-term safety, tolerability, and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in participants with cystic fibrosis.

Eligibility Criteria

This trial is for individuals with cystic fibrosis who previously participated in certain VX-121 studies and completed the treatment or visits, even if they had interruptions. It's not open to pregnant or breastfeeding women or those who couldn't tolerate the drug before.

Inclusion Criteria

I completed or was part of the VX20-121-102 or VX20-121-103 study without permanently stopping the study drug.

Exclusion Criteria

I am not pregnant or breastfeeding.

You had a bad reaction to the study drug in a previous study.

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 once daily

96 weeks

Treatment Part B

Participants continue to receive VX-121/TEZ/D-IVA once daily

48 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 is testing the long-term safety and effectiveness of a combination therapy called VX-121/TEZ/D-IVA designed for people with cystic fibrosis to see how well it works over an extended period.

Participant Groups

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

Part A: Participants will receive VX-121/TEZ/D-IVA once daily for 96 weeks. Part B: Participants will receive VX-121/TEZ/D-IVA once daily for an additional 48 weeks.

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]

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]

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]

Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination therapy for cystic fibrosis that significantly improves lung function, quality of life, and reduces exacerbations in patients aged 12 and older with at least one F508del mutation in the CFTR gene, surpassing existing treatments.

While the therapy shows promising efficacy, common side effects include rash and headache, and liver function monitoring is advised; however, about 10% of the cystic fibrosis population remains ineligible for this or any CFTR modulation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. Ridley, K., Condren, M.[2020]

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

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

3. 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]

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

VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. [2019]

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

VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease with the Phe508del/minimal function genotype. [2022]

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

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

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

Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. [2020]