VX-121 + Tezacaftor + Deutivacaftor for Cystic Fibrosis

Recruiting at 44 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, VX-121/TEZ/D-IVA (a combination therapy), for individuals with cystic fibrosis who have at least one specific genetic mutation (a change in the DNA). The trial aims to assess the treatment's effectiveness, safety, and movement through the body. Participants will receive the treatment in two parts, with adjustments based on initial results. It suits those with stable cystic fibrosis and at least one triple combination responsive mutation, but not those with certain liver issues or infections affecting lung health. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for cystic fibrosis.

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 has shown that the treatment VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) is generally safe for people with cystic fibrosis. Previous participants reported mostly mild to moderate side effects. Common side effects include headaches and some stomach issues, typical for many treatments. This combination therapy aims to improve the function of the CFTR protein, which malfunctions in cystic fibrosis. The treatment is in an advanced stage of study, having already passed earlier safety tests, which gives researchers confidence in its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cystic fibrosis?

Researchers are excited about VX-121 combined with Tezacaftor and Deutivacaftor for cystic fibrosis because it targets the root cause of the disease more effectively. Unlike other treatments that may only address symptoms or certain mutations, this combination focuses on improving the function of the CFTR protein, which is faulty in people with cystic fibrosis. By enhancing the protein's ability to move chloride ions across cell membranes, this treatment has the potential to significantly improve lung function and overall health outcomes for patients. This innovative approach could offer hope for better management of the disease compared to existing therapies.

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

Research shows that the combination of VX-121, tezacaftor, and deutivacaftor (VX-121/TEZ/D-IVA), which participants in this trial will receive, may help treat cystic fibrosis (CF). Studies have found that this combination can improve the function of the CFTR protein, which often malfunctions in people with CF. Better CFTR function can lead to improved lung health and overall well-being. Early results suggest that patients with at least one mutation in the CFTR gene that responds to this triple combination may benefit from the treatment. This supports the idea that VX-121/TEZ/D-IVA could effectively manage CF symptoms. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 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 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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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 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]

Citations

1. 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 ...

2. 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 ...

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. 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 ...

5. clinicaltrialsregister.eu clinicaltrialsregister.eu/ctr-search/trial/2021-000712-31/results

EudraCT Number 2021-000712-31 - Clinical trial results A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are ...

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 for ...

7. trial.medpath.com trial.medpath.com/clinical-trial/f744a555fcc3c903/nct05422222-vX-121-tezacaftor-deutivacaftor-cystic-fibrosis

Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF ... 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 ...