Trikafta for Cystic Fibrosis

No longer recruiting at 2 trial locations

Overseen By Rachel Linnemann, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must be taking: Trikafta

Must not be taking: CYP3A4 inhibitors/inducers

Disqualifiers: Drug/alcohol abuse, Transplant, 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: 35

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests Trikafta, a treatment designed to help people with cystic fibrosis (CF) who have specific gene mutations not currently approved for this medication. Researchers aim to assess Trikafta's effects on lung function and sweat chloride levels, both crucial in CF. They will also examine how the drug interacts with cells derived from participants' skin or blood to predict its effectiveness. The trial seeks individuals with CF who have either a partial function mutation or the N1303K variant and are stable without recent flare-ups. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must agree to adhere to all current medical therapies as designated by your CF care center physician. You should avoid certain medications that affect Trikafta, like CYP3A4 inhibitors or inducers, and grapefruit products.

Is there any evidence suggesting that Trikafta is likely to be safe for humans?

Research has shown that Trikafta has been tested in over 500 people with cystic fibrosis (CF) who have at least one F508del mutation. These studies, lasting up to 24 weeks, found that Trikafta is generally well-tolerated. Some participants experienced side effects, with the most serious being liver damage and liver failure, though these are rare.

Another study indicated that Trikafta is safe for children with CF and helps improve their lung function. While Trikafta is already a prescription medicine for CF, its safety for children under 2 years old remains unknown.

For those considering joining a trial, knowing that Trikafta has been tested in many people and is approved for CF can provide reassurance about its safety. However, it is crucial to be aware of possible side effects, especially those affecting the liver. ^{1 2 3 4 5}

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

Trikafta is unique because it targets the underlying cause of cystic fibrosis by using a combination of three medications—elexacaftor, tezacaftor, and ivacaftor—to improve the function of the CFTR protein. This is different from standard treatments that mainly manage symptoms without addressing the root problem. Researchers are excited because Trikafta has shown promise in improving lung function and quality of life for people with specific genetic mutations, potentially offering a more effective long-term solution for those with partial function or the N1303K variant.

What evidence suggests that Trikafta might be an effective treatment for cystic fibrosis?

Studies have shown that Trikafta greatly helps people with cystic fibrosis (CF). It reduces lung flare-ups by 63% and boosts lung function. People taking Trikafta also experience better overall health related to CF. In this trial, participants with specific CF gene mutations not yet approved for Trikafta will receive the treatment. The drug's success in other CF cases is encouraging, suggesting Trikafta might also help those with rare CF mutations. ^{6 7 8 9 10}

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 cystic fibrosis patients aged 12 or older who don't have the F508del mutation but may have partial function mutations or N1303K. They should be clinically stable, able to perform spirometry tests, and not on certain CFTR modulators. Participants must agree to use birth control and adhere to their current medical therapies.

Inclusion Criteria

Sweat Chloride < 80 mmol/L and/or pancreatic sufficiency (no exogenous pancreatic enzyme supplement therapy) or carrying the N1303K CFTR variant

You are capable of taking Trikafta medication.

You are willing to comply with all study procedures and are available for the duration of the study.

Exclusion Criteria

You have a record of drug or alcohol abuse in the past year.

You are allergic to Trikafta.

If the researchers believe that you may have a condition that could make it hard to study the drug or that could make taking the drug risky for you, you may not be able to participate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Trikafta for approximately four weeks to assess clinical endpoints such as FEV1 and sweat chloride

4 weeks

Baseline, Days 7, 14, 28

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life and weight

4 weeks

Days 28, 56

What Are the Treatments Tested in This Trial?

Interventions

• Trikafta

Trial Overview The study is testing Trikafta in a small group of cystic fibrosis patients with specific genetic profiles over four weeks. Researchers will monitor lung function and sweat chloride levels, as well as test patient-derived iPS cells in the lab to predict clinical response.

How Is the Trial Designed?

Group I: Substudy 2 - Participants who Encode the N1303K Variant Experimental Treatment 1 Intervention

Participants with CF who encode the N1303K variant will receive Trikafta for 28 days.

Group II: Substudy 1 - Participants With Evidence of Partial Function Experimental Treatment 1 Intervention

Participants with CF with evidence of partial function (sweat chloride \< 80 milliequivalents per liter (mEq/L) or pancreatic sufficiency) will receive Trikafta for 28 days.

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 University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Cystic Fibrosis Foundation

Collaborator

Trials

199

Recruited

37,800+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

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]

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]

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]

Elexacaftor/tezacaftor/ivacaftor, a triple-combination therapy, showed potential benefits for a 37-year-old cystic fibrosis patient with chronic lung allograft dysfunction, including improved pancreatic function and quality of life, despite no change in lung function as measured by forced expiratory volume.

The treatment was well-tolerated with no significant side effects, although careful monitoring of renal function and immunosuppressant levels is necessary, indicating that this therapy may be beneficial for select patients awaiting lung retransplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elexacaftor/Tezacaftor/Ivacaftor as a Bridge to Lung Retransplant in a Recipient With Cystic Fibrosis. FitzMaurice, TS., Nazareth, D., Iyer, K., et al.[2022]

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]

Citations

1. 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.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40379539/

LONGITUDE: An observational study of the long-term ... Conclusions: People with CF aged ≥12 years in the UK who initiated ELX/TEZ/IVA had sustained improvements in multiple CF-related health outcomes, consistent ...

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

Real-world safety and effectiveness of elexacaftor ... In this interim analysis, people with CF taking ELX/TEZ/IVA had a reduced frequency of PEx and improved lung function, with a lower frequency of all-cause ...

4. jmcp.org jmcp.org/doi/10.18553/jmcp.2023.29.6.599

Real-world outcomes and direct care cost before and after ... With the most recent approval of elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA), approximately 90% of the CF population is now eligible to ...

5. 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 ... ALYFTREK has shown greater reductions in sweat chloride compared to TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) in Phase 3 trials ...

6. trikafta.com trikafta.com/important-safety-information

Important Safety Information TRIKAFTA can cause serious liver damage and liver failure. Liver failure leading to transplantation and death has been seen in some people with or without a ...

7. trikaftahcp.com trikaftahcp.com/safety-profile

Safety Profile | TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor ... Safety data from 510 patients aged 12 years and older with CF with at least one F508del mutation in 2 double‑blind, controlled, Phase 3 trials of 24 weeks ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/212273s004lbl.pdf

TRIKAFTA® (elexacaftor, tezacaftor, and ivacaftor tablets The safety profile of TRIKAFTA is based on data from 510 CF patients aged 12 years and older in two double-blind, controlled trials of 24 weeks and 4 weeks.

9. trikafta.com trikafta.com/

TRIKAFTA® (elexacaftor/tezacaftor/ivacaftor and ivacaftor) TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) ... It is not known if TRIKAFTA is safe and effective in children under 2 years ...

10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38869349/

Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor ... Our data indicate that ETI therapy is well tolerated by children with CF and is effective in improving signs of lung function abnormalities from early ...