Elexacaftor/Tezacaftor/Ivacaftor for Cystic Fibrosis

Not currently recruiting at 19 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: Drug intolerance, Other trial participation, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the safety and effectiveness of a combination treatment called ELX/TEZ/IVA (Elexacaftor/Tezacaftor/Ivacaftor) for individuals with cystic fibrosis, a genetic condition affecting the lungs. Participants will take the medication in the morning and evening to assess its long-term effects. This trial suits those who have participated in a related study and completed the treatment period without stopping due to drug intolerance. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity 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 this trial's treatments are likely to be safe?

Research has shown that the medication elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is generally safe for people with cystic fibrosis. In a study with 510 patients, most tolerated the treatment well over 24 weeks, and severe side effects were uncommon. However, serious liver problems have been reported, though these cases are rare. Overall, the treatment appears safe and beneficial in the long term, making it a promising option for those with the F508del mutation in cystic fibrosis. ^{1 2 3 4 5}

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

Researchers are excited about Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) for cystic fibrosis because it targets the root cause of the disease more effectively than many existing treatments. Most cystic fibrosis medications focus on alleviating symptoms, but ELX/TEZ/IVA works by improving the function of the defective CFTR protein that causes the condition. This triple combination therapy has the potential to significantly enhance lung function and reduce pulmonary exacerbations, offering hope for improved quality of life for patients. Unlike earlier therapies that only targeted specific mutations, ELX/TEZ/IVA is designed to benefit a broader range of cystic fibrosis patients.

What evidence suggests that ELX/TEZ/IVA is effective for cystic fibrosis?

Research has shown that the combination of Elexacaftor, Tezacaftor, and Ivacaftor (ELX/TEZ/IVA), which participants in this trial will receive, effectively treats cystic fibrosis. Studies have found that patients using this treatment experienced 63% fewer lung flare-ups compared to those taking a placebo. Additionally, patients reported better lung function, easier breathing, and fewer hospital visits. Another study found that this treatment also led to fewer lung infections and improved overall health. These consistent improvements suggest that ELX/TEZ/IVA can greatly help manage cystic fibrosis symptoms. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 12 or older with cystic fibrosis who completed treatment in a prior study (VX22-445-122 Part B) or had interruptions but didn't stop the drug and finished all visits up to the last scheduled one.

Inclusion Criteria

I finished or partially completed the VX22-445-122 Part B study without quitting the study drug.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ELX/TEZ/IVA in the morning and IVA in the evening to evaluate long-term safety, tolerability, efficacy, and pharmacodynamics

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ELX/TEZ/IVA
• IVA

Trial Overview The study aims to assess long-term safety, tolerability, effectiveness, and pharmacodynamics of a combination medication (ELX/TEZ/IVA) compared to ivacaftor alone in treating cystic fibrosis.

How Is the Trial Designed?

Group I: ELX/TEZ/IVA Experimental Treatment 2 Interventions

Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening.

ELX/TEZ/IVA is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Trikafta for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

Approved in European Union as Kaftrio for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

Approved in Canada as Trikafta for:

• Cystic fibrosis in patients aged 2 years and older with at least one copy of the F508del mutation in the CFTR gene or another mutation responsive to treatment

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 study of 65 lung transplant candidates with advanced cystic fibrosis, treatment with elexacaftor-tezacaftor-ivacaftor led to a significant improvement in lung function, with a median increase of 13.4% in forced expiratory volume after one month, which remained stable over a year.

The treatment also greatly reduced the need for other medical interventions, with an 86% decrease in intravenous antibiotics and a 59% reduction in oxygen therapy, allowing most patients to defer lung transplantation safely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis. Martin, C., Reynaud-Gaubert, M., Hamidfar, R., et al.[2022]

The combination therapy of Elexacaftor-Tezacaftor-Ivacaftor (ELX-TEZ-IVA) significantly improves lung function in patients with cystic fibrosis, demonstrating its efficacy as a treatment option.

A case report highlights that while rash is a common adverse effect of this therapy, it can resolve spontaneously without the need to stop treatment, indicating variability in how patients may react to the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of Elexacaftor-Tezacaftor-Ivacaftor induced rash resolving without interruption of treatment. Bhaskaran, D., Bateman, K.[2022]

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]

The combination therapy of elexacaftor, ivacaftor, and tezacaftor (Trikafta™) has shown significant improvements in lung function and quality of life for cystic fibrosis patients with the F508del mutation, based on multinational phase II and III studies.

In October 2019, this treatment was approved by the US FDA for patients aged 12 and older with at least one F508del mutation, marking a major advancement in cystic fibrosis therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/Ivacaftor/Tezacaftor: First Approval. Hoy, SM.[2020]

In a review of safety data from 14 clinical trials involving 1,711 participants, the rates of depression-related adverse events in patients with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) were similar to those in the placebo group, indicating no increased risk associated with the treatment.

Postmarketing data from 61,499 patients showed low exposure-adjusted rates of depression-related events, and patterns of depression prevalence did not change after starting ELX/TEZ/IVA, suggesting that any reported depression symptoms are consistent with the background rates in the cystic fibrosis population rather than being caused by the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. Ramsey, B., Correll, CU., DeMaso, DR., et al.[2023]

In a study of 16,116 cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) for an average of 20.4 months, there was a significant 79% reduction in pulmonary exacerbations and a 74% reduction in hospitalizations compared to the 5-year pre-treatment period.

The treatment also led to sustained improvements in lung function (average increase of 8.9 percentage points in forced expiratory volume in 1 second by Year 2), increased body mass index, and a notable decrease in the rates of death (72% lower) and lung transplantation (85% lower) compared to the year before the treatment became available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study. Bower, JK., Volkova, N., Ahluwalia, N., et al.[2023]

In a cohort study of 33 adults with cystic fibrosis, treatment with the triple CFTR modulator Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) led to significant improvements in glucose tolerance, with nearly half of the patients showing better glucose control after about 6 months of treatment.

The study also found significant reductions in blood glucose levels during an oral glucose tolerance test and improvements in HbA1c levels, suggesting that ELX/TEZ/IVA may enhance metabolic health in cystic fibrosis patients without increasing insulin secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis. Steinack, C., Ernst, M., Beuschlein, F., 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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40209082/

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/ ... Participants had sustained improvements in lung function, respiratory symptoms, CFTR function, pulmonary exacerbation rates, and nutritional status. The ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1569199325014675

LONGITUDE: An observational study of the long-term ... LONGITUDE is an observational, registry-based cohort study using data from the UK CF Registry to evaluate outcomes of ELX/TEZ/IVA in people aged ≥6 years.

3. trikafta.com trikafta.com/study-information

Studies and Results | TRIKAFTA® (elexacaftor/tezacaftor ... Through 24 weeks, the number of pulmonary exacerbations significantly decreased by 63% for people taking TRIKAFTA compared with placebo.

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2023.29.6.599

Real-world outcomes and direct care cost before and after ... Among 494 commercially insured members diagnosed with cystic fibrosis, a meaningful decrease in hospitalizations, emergency department visits, ...

5. atsjournals.org atsjournals.org/doi/10.1513/AnnalsATS.202102-220RL

Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Advanced ... Strikingly, there were nearly 2.4 fewer exacerbations per patient, or a 63% reduction, in the 12 months after treatment compared with before treatment. This is ...

6. trikaftahcp.com trikaftahcp.com/safety-profile

Safety Profile | TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor ... Safety data from 510 patients aged 12 years and older with CF with at least one F508del mutation in 2 double‑blind, controlled, Phase 3 trials of 24 weeks ...

7. trikafta.com trikafta.com/important-safety-information

Important Safety Information TRIKAFTA can cause serious liver damage and liver failure. Liver failure leading to transplantation and death has been seen in some people with or without a ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1569199323000668

Real-world safety and effectiveness of elexacaftor ... Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 ...

9. trikafta.com trikafta.com/

TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) in people aged 2 years and older who have at least one copy of the F508del ...