Trikafta for Bronchiectasis

Overseen By Randy Hunt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Cystic fibrosis, Cirrhosis, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Trikafta, a medication, to determine if it can improve symptoms and quality of life for individuals with non-cystic fibrosis bronchiectasis, a lung condition causing persistent cough and mucus buildup. Participants will take Trikafta for four weeks while researchers monitor health improvements and quality of life. The trial targets those with a specific genetic mutation related to cystic fibrosis who have remained stable without worsening symptoms for the past four weeks. Participants must have radiologic and clinical evidence of bronchiectasis and be able to perform certain lung function tests. As a Phase 4 trial, Trikafta is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications, but you must agree to adhere to all current medical therapies as designated by the study physician. Some medications, like those affecting CYP3A4, may not be allowed.

What is the safety track record for Trikafta?

Research shows that Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, is generally well-tolerated by patients. In studies with cystic fibrosis patients, Trikafta has significantly improved lung function. These studies also closely monitor safety.

Most side effects were mild, such as headaches and stomach issues. However, some patients experienced more serious effects, like liver problems, highlighting the importance of regular check-ups. This treatment is already approved for cystic fibrosis, providing reassurance about its safety. The current trial examines its effectiveness for non-cystic fibrosis bronchiectasis, a condition where the airways are widened and inflamed.

Since this trial is in a later stage, extensive safety data is already available. This indicates the treatment has undergone multiple tests to ensure safety for more people. As always, those considering joining a trial should consult a healthcare professional about any concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Trikafta is unique because it targets the underlying cause of bronchiectasis in people with certain CFTR mutations, which is not addressed by standard treatments like antibiotics or mucus thinners. Most current treatments focus on managing symptoms by clearing mucus or fighting infections, but Trikafta works by improving the function of the faulty protein caused by CFTR mutations. Researchers are excited about Trikafta because it offers a more precise approach, potentially improving lung function and quality of life for patients with bronchiectasis linked to these genetic mutations.

What is the effectiveness track record for Trikafta in treating non-cystic fibrosis bronchiectasis?

Research shows that Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, effectively treats lung conditions. In this trial, participants with non-cystic fibrosis bronchiectasis (NCFBE) and either one known CFTR mutation or mildly elevated sweat chloride measurements will receive Trikafta for four weeks. Studies have found that Trikafta improves lung function, reduces symptoms, and enhances quality of life. Patients in these studies experienced fewer flare-ups of lung symptoms after using this treatment. Additionally, reports indicate better weight management and slower symptom progression with Trikafta. These findings strongly suggest that Trikafta could be effective for those with NCFBE. ^{1 2 4 6 7}

Who Is on the Research Team?

Eric Sorscher, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with non-cystic fibrosis bronchiectasis who can perform spirometry tests and have a certain level of lung function. Participants must not be pregnant, breastfeeding, or have used CFTR modulators in the last 6 months. They should agree to use birth control during the study and remain clinically stable without exacerbations for 4 weeks prior.

Inclusion Criteria

I have a CF mutation or my sweat chloride test shows 30-59 mEq/L.

My lung function test meets specific standards and my FEV1 score is between 40-90% of the expected value.

I can take Trikafta without any issues.

Exclusion Criteria

I am not taking any medications or consuming products that affect Trikafta.

You are allergic to Trikafta.

I haven't had worsening lung symptoms or changes in my lung treatment in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Trikafta for four weeks to assess clinical endpoints, quality of life, and weight.

4 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in FEV1, sweat chloride, and quality of life.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Trikafta

Trial Overview

The trial is testing Trikafta on patients with non-cystic fibrosis bronchiectasis over four weeks, monitoring clinical outcomes, quality of life, and weight changes. It also involves collecting skin samples to examine cellular responses to the medication.

How Is the Trial Designed?

Group I: Trikafta Experimental Treatment 1 Intervention

Participants with NCFBE and one known CFTR mutation and/or mildly elevated sweat chloride measurements (i.e., 30-60 mEq/L) receiving Trikafta for four weeks.

Trikafta 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 who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data

Approved in European Union as Trikafta/Kaftrio for:

• Cystic fibrosis in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data

Approved in Canada as Trikafta for:

• Cystic fibrosis in patients aged 2 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or a mutation in the CFTR gene that is responsive based on in vitro data

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

The Marcus Foundation

Collaborator

Trials

19

Recruited

2,200+

The Marcus Foundation, Inc.

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 74 adults with cystic fibrosis, the initiation of elexacaftor/tezacaftor/ivacaftor (E/T/I) therapy showed no significant changes in liver fibrosis markers, except for an increase in the AST-to-platelet-ratio index (APRI).

Notably, patients with higher baseline liver stiffness measurements (LSM) experienced a significant reduction in LSM after starting E/T/I, suggesting a potential positive effect of the treatment in those with severe cystic fibrosis liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of elexacaftor/tezacaftor/ivacaftor on liver fibrosis markers in adults with cystic fibrosis. Tewkesbury, DH., Scott, J., Barry, PJ., 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]

A 7-year-old boy with cystic fibrosis experienced a severe skin reaction to the CFTR modulator elexacaftor/tezcaftor/ivacaftor (Trikafta), highlighting the potential for adverse reactions to these important medications.

Desensitization was successfully implemented, allowing the patient to continue treatment, which underscores the importance of managing drug reactions to maintain access to essential therapies for cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

If At First You Don't Succeed, Trikafta Again. Loyd, I., Papac, N., Hirshburg, J., et al.[2022]

In a case series of 15 adults with cystic fibrosis who experienced adverse effects from elexacaftor/tezacaftor/ivacaftor (ETI), dose reduction led to clinical stability and resolution or improvement of adverse effects in 13 patients, indicating that lower doses can maintain therapeutic efficacy.

Pharmacokinetic modeling predicted that lung concentrations of the reduced ETI doses remained above the effective concentration needed for drug efficacy, supporting the idea that dose reduction can be a viable strategy for managing side effects while still providing benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of elexacaftor/tezacaftor/ivacaftor dose reduction: Mechanistic exploration through physiologically based pharmacokinetic modeling and a clinical case series. Hong, E., Li, R., Shi, A., et al.[2023]

In a study of 114 cystic fibrosis patients treated with elexacaftor/tezacaftor/ivacaftor (ETI) for 30 months, lung function significantly improved from an average FEV1% of 37.5 to 48.6, indicating enhanced respiratory health.

ETI treatment also led to a substantial reduction in the number of exacerbations from 3.9 to 0.9 per year, improved body mass index (BMI), and was well-tolerated with minimal side effects, demonstrating its efficacy and safety in managing advanced cystic fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease. Carrasco Hernández, L., Girón Moreno, RM., Balaguer Cartagena, MN., et al.[2023]

In a study of 438 participants with cystic fibrosis, treatment with elexacaftor/tezacaftor/ivacaftor (ETI) led to small but statistically significant improvements in gastrointestinal symptoms after 6 months, as measured by validated questionnaires.

While there was a notable decrease in fecal calprotectin, indicating reduced inflammation, other markers of pancreatic function did not show meaningful improvement, suggesting that ETI primarily benefits pulmonary health rather than gastrointestinal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. Schwarzenberg, SJ., Vu, PT., Skalland, M., 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 43 cystic fibrosis patients, treatment with elexacaftor/tezacaftor/ivacaftor led to significant improvements in lung function, with FEV-1 increasing from 65% to 76% predicted after 3 months (p = 0.0000005).

Patients also reported enhanced sinonasal health and overall quality of life, as indicated by improvements in the SNOT-22 and CFQ-R scores, demonstrating a strong correlation between respiratory health and sinonasal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of highly effective modulator therapy on quality of life in adults with cystic fibrosis. DiMango, E., Spielman, DB., Overdevest, J., et al.[2021]

A new case of urticaria multiforme-type drug reaction was identified in a patient taking Trikafta, a medication for cystic fibrosis, highlighting a potential side effect of this treatment.

This information can help clinicians better prepare to recognize and manage similar adverse reactions in patients starting Trikafta.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel reaction to new cystic fibrosis medication Trikafta. Stashower, J., Carr, P., Miller, V., et al.[2021]

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]

Citations

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publications.ersnet.org

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Treatment with ETI improved lung function, symptoms, quality of life and lead to a significant reduction in annual pulmonary exacerbations.

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Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) ...

Evaluating elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta™) for treatment of patients with non-cystic fibrosis bronchiectasis (NCFBE): A ...

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clinicaltrials.gov

clinicaltrials.gov/study/NCT05743946

Trikafta for Patients With Non-cystic Fibrosis Bronchiectasis

This study is an open-label, single center trial of orally administered elexacaftor, tezacaftor and ivacaftor (Trikafta) that will enroll 30 patients with NCFBE ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S2213007125001005

Clinical efficacy of elexacaftor-tezacaftor-ivacaftor in two ...

Clinical data were collected before and after Trikafta initiation, including pulmonary function, weight, microbiological status, and symptom progression.

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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.

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12548744/

Real-World Outcomes of Elexacaftor/Tezacaftor/Ivacaftor in ...

These data highlight the need for future studies in children to determine whether residual infection continues to drive inflammation and, ...

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Multisystemic Effects of Elexacaftor–Tezacaftor–Ivacaftor in ...

Data from randomized clinical trials (4–6) revealed improvement in respiratory outcomes (respiratory symptoms, lung function, and exacerbations) ...