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

Trial Summary

What is the purpose of this trial?

This trial will test Trikafta, a medication that helps lung proteins work better, on patients with non-cystic fibrosis bronchiectasis. These patients have lung issues similar to cystic fibrosis but do not respond to typical treatments. The goal is to see if Trikafta can improve their lung health by clearing mucus and bacteria from their airways.

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 data supports the effectiveness of the drug Trikafta for bronchiectasis?

Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, has been shown to improve lung function and quality of life in patients with cystic fibrosis, a condition that affects the lungs similarly to bronchiectasis. This suggests it might also help improve lung function in bronchiectasis patients. ^{1 2 3 4 5}

What safety information is available for Trikafta (elexacaftor/tezacaftor/ivacaftor)?

Trikafta, also known as elexacaftor/tezacaftor/ivacaftor, has been associated with some side effects like skin rashes and liver issues in people with cystic fibrosis. Some patients have managed these side effects by adjusting the dose, and in some cases, the rashes resolved without stopping the treatment. ^{1 6 7 8 9}

How is the drug Trikafta unique for treating bronchiectasis?

Trikafta is unique because it combines three components (elexacaftor, tezacaftor, and ivacaftor) that work together to improve lung function, originally developed for cystic fibrosis, a condition with similar lung issues. This combination targets the underlying cause of the disease, which is different from standard treatments that mainly address symptoms. ^{1 3 5 6 10}

Research Team

Eric Sorscher, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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, 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 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]

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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Novel reaction to new cystic fibrosis medication Trikafta. [2021]

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

Effect of highly effective modulator therapy on quality of life in adults with cystic fibrosis. [2021]

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

Elexacaftor/tezacaftor/ivacaftor and gastrointestinal outcomes in cystic fibrosis: Report of promise-GI. [2023]

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

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

5. Spain pubmed.ncbi.nlm.nih.gov

Experience With Elexacaftor/Tezacaftor/Ivacaftor in Patients With Cystic Fibrosis and Advanced Disease. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

If At First You Don't Succeed, Trikafta Again. [2022]

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

Safety of elexacaftor/tezacaftor/ivacaftor dose reduction: Mechanistic exploration through physiologically based pharmacokinetic modeling and a clinical case series. [2023]

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

Effects of elexacaftor/tezacaftor/ivacaftor on liver fibrosis markers in adults with cystic fibrosis. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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