Trikafta for Cystic Fibrosis

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

42 Participants Needed

Trial Summary

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 Trikafta safe for humans?

Trikafta, a combination of elexacaftor, tezacaftor, and ivacaftor, has been shown to be generally safe in clinical trials for people with cystic fibrosis aged 12 and older, though some may experience drug reactions like skin rashes. It's important to be aware of potential drug interactions and consult healthcare providers for personalized advice. ^{1 2 3 4 5}

What makes the drug Trikafta unique for treating cystic fibrosis?

Trikafta is unique because it combines three components—elexacaftor, tezacaftor, and ivacaftor—that work together to improve lung function and quality of life in cystic fibrosis patients with the F508del mutation. This combination targets the underlying cause of the disease more effectively than previous treatments, which often focused on managing symptoms rather than addressing the root problem. ^{2 4 6 7 8}

What is the purpose of this trial?

This trial will test Trikafta on cystic fibrosis patients with rare mutations not currently approved for this treatment. The study aims to see if lab-grown cells from these patients can predict how well they will respond to Trikafta. This could help more patients with rare mutations get effective treatments. Trikafta is a combination therapy consisting of elexacaftor, tezacaftor, and ivacaftor, which has shown effectiveness in treating certain CFTR mutations.

Research Team

Eric Sorscher, MD

Principal Investigator

Emory University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: 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: Participants With Evidence of Partial Function (sweat chloride < 80 mEq/L or pancreatic sufficiency) 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+

Findings from Research

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]

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]

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]

References

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

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

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

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

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

Drug-drug interactions with CFTR modulator therapy in cystic fibrosis: Focus on Trikafta®/Kaftrio®. [2023]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Physiologically Based Pharmacokinetic Modeling of CFTR Modulation in People with Cystic Fibrosis Transitioning from Mono or Dual Regimens to Triple-Combination Elexacaftor/Tezacaftor/Ivacaftor. [2021]

6. Turkey pubmed.ncbi.nlm.nih.gov

Elexacaftor/Tezacaftor/Ivacaftor as a Bridge to Lung Retransplant in a Recipient With Cystic Fibrosis. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

CFTR modulator use in post lung transplant recipients. [2022]