ELX/TEZ/IVA for Cystic Fibrosis

Not currently recruiting at 99 trial locations

Overseen By Medical Information

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Must be taking: ELX/TEZ/IVA

Disqualifiers: Study drug intolerance, 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 treatment called ELX/TEZ/IVA (also known as Trikafta or Kaftrio) for individuals with cystic fibrosis (CF), a genetic condition affecting breathing and digestion. The trial aims to assess the long-term safety and effectiveness of this treatment. Participants will take the medication in two parts, each lasting 96 weeks. Those who have previously used this treatment in another study and completed their visits may be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the potential availability of a new 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 this trial's treatments are likely to be safe?

Research has shown that ELX/TEZ/IVA is generally safe and well-tolerated for people with cystic fibrosis. In previous studies, this treatment improved lung function and reduced lung flare-ups by 63%. These studies also found fewer hospital visits and better overall health over time. Another study confirmed its long-term safety for both teenagers and adults. While these results are promising, discussing this information with a healthcare provider is important to understand its relevance to individual cases. ^{1 2 3 4 5}

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

Researchers are excited about ELX/TEZ/IVA for cystic fibrosis because it targets the root cause of the disease by enhancing the function of the CFTR protein, which is faulty in people with this condition. Unlike older treatments that primarily focus on managing symptoms, ELX/TEZ/IVA works by correcting the defective protein's function. This approach has the potential to significantly improve lung function and overall health outcomes for patients, offering hope for more effective and comprehensive management of cystic fibrosis.

What evidence suggests that ELX/TEZ/IVA might be an effective treatment for cystic fibrosis?

Research has shown that the combination treatment ELX/TEZ/IVA works well for people with cystic fibrosis (CF). One study found that individuals using this treatment experienced 63% fewer lung flare-ups compared to those not using it. Other studies have demonstrated improved lung function and reduced salt levels in sweat, an important indicator of CF. Additionally, real-world evidence indicates fewer hospital visits for those on ELX/TEZ/IVA. These findings suggest that ELX/TEZ/IVA could be a promising option for managing CF symptoms. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people with cystic fibrosis who have at least one non-F508del mutation responsive to the drug combo ELX/TEZ/IVA. Participants should have completed treatment in a previous study or, if interrupted, made it to the last scheduled visit of that study's treatment period.

Inclusion Criteria

Completed study drug treatment in parent study or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the treatment period in the parent study

Exclusion Criteria

You had trouble tolerating 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 ELX/TEZ/IVA in the morning and IVA in the evening

96 weeks

Treatment Part B

Participants continue to receive ELX/TEZ/IVA in the morning and IVA in the evening

96 weeks

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 trial is testing the long-term safety and effectiveness of a drug combination called Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) for treating cystic fibrosis in patients without the F508del mutation.

How Is the Trial Designed?

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

Part A: Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening for 96 weeks. Part B: Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening for an additional 96 weeks.

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 13 lung transplant recipients (LTRs) using elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), the therapy was found to be poorly tolerated, with 38.4% of patients discontinuing due to issues like declining pulmonary function and mood disturbances.

Despite the challenges, 46.2% of patients reported improvements in sinus symptoms and a significant reduction in tacrolimus dose requirements (by 50%), indicating some therapeutic benefit for extrapulmonary cystic fibrosis manifestations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor tolerability of cystic fibrosis transmembrane conductance regulator modulator therapy in lung transplant recipients. Doligalski, CT., McKinzie, CJ., Yang, A., et al.[2022]

In a study involving eight cystic fibrosis patients with the N1303K mutation, treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) led to significant improvements in lung function, with an average increase of 18.4 percentage points in forced expiratory volume after 8 weeks.

The treatment also resulted in a notable increase in body mass index (BMI) and improvements in CFTR channel activity in intestinal organoids, indicating that ELX/TEZ/IVA can provide clinical benefits for patients with the N1303K mutation, despite it not being included in the original list of responsive mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and functional efficacy of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis carrying the N1303K mutation. Sadras, I., Kerem, E., Livnat, G., 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 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 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]

Citations

1. news.vrtx.com news.vrtx.com/news-releases/news-release-details/vertex-presents-new-data-across-portfolio-cystic-fibrosis

Vertex Presents New Data Across Portfolio of Cystic Fibrosis ... “Real-world outcomes in people with cystic fibrosis treated with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) with up to four years of follow- ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12365565/

Efficacy of Trikafta (ELX/TEZ/IVA) & Symdeko (TEZ/IVA) in ... Its efficacy, as demonstrated by significant improvements in FEV1 levels, reduction in sweat chloride levels, and enhanced Cystic Fibrosis Questionnaire-Revised ...

3. 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.

4. 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.

5. 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, ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40209082/

Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/ ... These results confirm the favorable long-term safety profile and durable disease-modifying clinical benefits of ELX/TEZ/IVA in adolescents and adults with CF.

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

Real-world safety and effectiveness of elexacaftor ... ELX/TEZ/IVA treatment was associated with sustained improvements in lung function, reduced frequency of PEx and all-cause hospitalization, increased BMI, and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04183790

Evaluation of Long-term Safety and Efficacy of ELX/TEZ ... The study evaluates the long-term safety, tolerability, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with ...