ELX/TEZ/IVA for Cystic Fibrosis

No longer recruiting at 19 trial locations

Overseen By Medical Information

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Vertex Pharmaceuticals Incorporated

Disqualifiers: History of illness, 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 combination treatment called ELX/TEZ/IVA (also known as Trikafta or Kaftrio) for children with cystic fibrosis (CF), a condition affecting the lungs and digestive system. The goal is to understand how the body processes these drugs, assess their safety, and evaluate their effectiveness. The trial consists of two parts: participants receive the treatment in the morning and an additional drug in the evening, with adjustments based on early results. It suits children with a specific genetic mutation linked to CF. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering a promising opportunity for children to access potentially life-changing therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinator or your doctor for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that ELX/TEZ/IVA is generally easy for people to tolerate. Studies have found that those taking this treatment experience fewer lung flare-ups, improved lung function, and fewer hospital visits. Long-term research confirms that ELX/TEZ/IVA is safe and provides lasting benefits for people with cystic fibrosis (CF).

Research indicates that IVA, or ivacaftor, helps improve lung function and weight in people with CF. Ivacaftor is approved for use in babies as young as one month who have specific CF gene mutations, suggesting it is safe for young children. Studies in older patients also support its safety and effectiveness.

In summary, both treatments have strong safety records. They are well-researched and considered safe for people with CF, including young children. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ELX/TEZ/IVA for cystic fibrosis because it targets the underlying cause of the condition rather than just managing symptoms. Unlike standard treatments that primarily address the symptoms or improve lung function, ELX/TEZ/IVA works by correcting the defective CFTR protein, which is the root cause of cystic fibrosis. This approach has the potential to significantly improve lung function and overall health, offering a more comprehensive solution for patients. Additionally, the combination of three active ingredients in ELX/TEZ/IVA provides a more robust treatment, potentially benefiting a broader range of cystic fibrosis patients compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for cystic fibrosis?

Research has shown that Trikafta (ELX/TEZ/IVA) effectively treats cystic fibrosis. Studies found it improved lung function and lowered sweat chloride levels, both key disease markers. Patients experienced 63% fewer lung flare-ups and required fewer hospital visits. In this trial, participants will take ELX/TEZ/IVA in the morning and Ivacaftor (IVA) in the evening. Previous studies demonstrated that Ivacaftor reduced lung flare-ups by about 42% and hospital stays by 30%. Both treatments have provided lasting improvements in lung health and overall well-being for people with cystic fibrosis. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for young children aged 12 to less than 24 months with Cystic Fibrosis who have at least one F508del mutation or another mutation responsive to the study drugs. Children should not have other illnesses that could confuse the results or increase risks from the study drugs.

Inclusion Criteria

I have a specific mutation in my CF gene that responds to certain treatments.

Exclusion Criteria

History of any illness or any clinical condition that, in the opinion of the investigator, might either confound the results of the study or pose an additional risk in administering study drug(s) to the participant

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

8 weeks

Treatment Part B

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

• ELX/TEZ/IVA
• IVA

Trial Overview

The trial is testing ELX/TEZ/IVA, a combination of medications for Cystic Fibrosis, in very young children. It aims to understand how this medication works in their bodies and its safety, tolerability, and effectiveness.

How Is the Trial Designed?

Group I: Part B Experimental Treatment 2 Interventions

Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening with the dose(s) to be based on the outcome of Part A.

Group II: Part A 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 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 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 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 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 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]

Citations

1.

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 ...

2.

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- ...

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.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK603345/

Clinical Review - Elexacaftor-Tezacaftor-Ivacaftor ... - NCBI - NIH

The objective of this review was to evaluate the beneficial and harmful effects of ELX-TEZ-IVA at recommended dosages for the treatment of patients aged 6 years ...