VX-121 Combination Therapy for Cystic Fibrosis

Not currently recruiting at 220 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination therapy, VX-121/TEZ/D-IVA, to determine its safety and effectiveness for individuals with cystic fibrosis, a condition that causes lung problems and other health issues. Participants will take the treatment daily for up to 144 weeks. Suitable candidates for this trial include those who have participated in specific earlier studies with this treatment and completed all required visits. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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 VX-121/TEZ/D-IVA is likely to be safe for humans?

Research shows that the combination treatment VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) has undergone safety testing in people with cystic fibrosis. Studies have found that this treatment is generally well-tolerated, with most people experiencing no serious issues. Some side effects have been reported, but they were mostly mild to moderate, similar to those seen with other cystic fibrosis treatments.

This treatment is currently in phase 3 studies, indicating that earlier research has demonstrated its safety for further testing. This phase aims to confirm its safety and effectiveness in a larger group. These studies help ensure the treatment's safety for long-term use. Discuss any concerns with a healthcare provider to determine if this trial is suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about VX-121/TEZ/D-IVA for cystic fibrosis because it combines three compounds that target the root cause of the disease: the malfunctioning CFTR protein. Unlike current treatments like ivacaftor, lumacaftor, and tezacaftor, which help some CFTR proteins function better, VX-121 offers a new way to potentially improve the protein's stability and function more effectively. This combination therapy could lead to better lung function and overall health for people with cystic fibrosis, offering hope for a more comprehensive approach to managing the disease.

What evidence suggests that VX-121/TEZ/D-IVA might be an effective treatment for cystic fibrosis?

Research has shown that the treatment VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA), which participants in this trial will receive, aims to help people with cystic fibrosis by improving the function of the CFTR protein. This protein plays a crucial role in controlling the balance of salt and water in the lungs. Studies have found that this treatment can enhance lung function by improving CFTR protein performance. Participants in earlier studies experienced better breathing and overall health. These improvements offer promise for those with cystic fibrosis. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05422222

Study Details | NCT05422222 | Evaluation of VX-121/ ... The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05422222?term=Vertex&cond=Cystic%20Fibrosis&aggFilters=status:not%20rec%20enr%20act&viewType=Table&rank=9

Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

3. clinicaltrials.vrtx.com clinicaltrials.vrtx.com/studies/nct05422222?condition%5Beq%5D=Cystic+Fibrosis

Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic ... The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF ...

4. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/61992/translate/en/?cHash=6e165a9c3414c3ffd218086a4ceb1636

Assessment of VX-121/Tezacaftor/Deutivacaftor in ... This is a multicenter phase III study to assess the safety, tolerability, and efficacy of the DK therapy VX-121/TEZ/D-IVA in participants with cystic fibrosis ...

5. apps.cff.org apps.cff.org/Trials/Finder?search=%7BPipelineDrugId%3A%2710166%27%2CPipelineDrugDisplayName%3A%27VX-121+%2B+tezacaftor+%2B+VX-561%27%7D

Clinical Trials Finder This study will look at the safety and effectiveness of VX-121/tezacaftor/deutivacaftor, a drug combination intended to help CFTR protein function closer to ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05033080

NCT05033080 | A Phase 3 Study of VX-121 Combination ... The purpose of this study evaluates the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who were heterozygous ...

7. clinicaltrials.vrtx.com clinicaltrials.vrtx.com/studies/nct05444257?condition%5Beq%5D=Cystic+Fibrosis

A Study Evaluating the Long-term Safety and Efficacy of VX ... 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 ...