Elexacaftor/Tezacaftor/Ivacaftor for Cystic Fibrosis

Recruiting at 16 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

50 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 Elexacaftor/Tezacaftor/Ivacaftor for cystic fibrosis?

Research shows that Elexacaftor/Tezacaftor/Ivacaftor improves lung function, body weight, and quality of life in people with cystic fibrosis. It also reduces infection-related doctor visits and the need for antibiotics, indicating its effectiveness in managing the condition. ^{1 2 3 4 5}

Is Elexacaftor/Tezacaftor/Ivacaftor safe for humans?

Elexacaftor/Tezacaftor/Ivacaftor (also known as Trikafta or Kaftrio) has been shown to be generally safe in people with cystic fibrosis, including children as young as 6 years old. Some reported side effects include rash and depression-related events, but these are not common and often resolve without stopping the treatment. ^{5 6 7 8 9}

What makes the drug Elexacaftor/Tezacaftor/Ivacaftor unique for treating cystic fibrosis?

Elexacaftor/Tezacaftor/Ivacaftor is unique because it combines three CFTR modulators to specifically target the most common cystic fibrosis mutation (F508del), leading to significant improvements in lung function and quality of life for patients with this mutation. ^{1 3 10 11 12}

What is the purpose of this trial?

The purpose of the study is to evaluate the long-term safety, tolerability, efficacy, and pharmacodynamics (PD) of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA).

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Improved glucose tolerance after initiation of Elexacaftor / Tezacaftor / Ivacaftor in adults with cystic fibrosis. [2023]

2. 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]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis. [2022]

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

The Rapid Reduction of Infection-Related Visits and Antibiotic Use Among People With Cystic Fibrosis After Starting Elexacaftor-Tezacaftor-Ivacaftor. [2023]

5. Netherlands 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. [2023]

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

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Children Aged ⩾6 Years with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Clinical Trial. [2023]

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

Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis and at least one F508del allele: 144-week interim results from a 192-week open-label extension study. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

A case of Elexacaftor-Tezacaftor-Ivacaftor induced rash resolving without interruption of treatment. [2022]

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

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

11. New Zealand pubmed.ncbi.nlm.nih.gov

Elexacaftor/Ivacaftor/Tezacaftor: First Approval. [2020]

12. 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]