Symdeko for Cystic Fibrosis
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Alabama at Birmingham
Must not be taking: Antibiotics, Steroids, others
Disqualifiers: Smoking, Transplant, Cirrhosis, ESRD, others
No Placebo Group
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?The purpose of this study is to explore the use of off-label CFTR modulators that may affect CFTR function in patients with CFTR mutations that are not currently approved for these drugs.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop your current medications, but it excludes those taking medications with significant drug interactions with CFTR modulators. It's best to discuss your specific medications with the study team.
What data supports the effectiveness of the drug Symdeko for treating cystic fibrosis?
Research shows that the combination of tezacaftor and ivacaftor, which is part of Symdeko, is effective in improving lung function and quality of life in people with cystic fibrosis. It has a favorable safety profile and is particularly beneficial for those with specific genetic mutations related to cystic fibrosis.
12345Is Symdeko (tezacaftor/ivacaftor) safe for people with cystic fibrosis?
Symdeko (tezacaftor/ivacaftor) has been studied for safety in people with cystic fibrosis, especially those who had to stop another treatment due to breathing problems. It generally has a good safety profile, but some people may experience side effects like rash or headache, and liver function should be monitored.
45678How is the drug Symdeko different from other cystic fibrosis treatments?
Symdeko, which combines tezacaftor and ivacaftor, is unique because it targets the underlying cause of cystic fibrosis by helping the defective protein function better, specifically for those with certain genetic mutations. This approach is different from treatments that only manage symptoms, offering a more targeted therapy for improving lung function and overall health in eligible patients.
5791011Eligibility Criteria
This trial is for individuals with Cystic Fibrosis, aged 6 or older, who have specific CFTR mutations that might respond to certain drugs not yet approved for their condition. They must be on a stable CF treatment and able to give consent. People can't join if they have severe liver or kidney disease, had an organ transplant, are currently in another drug study, smoked recently, or take medications that don't mix well with the trial drugs.Inclusion Criteria
I am 6 years old or older.
My CFTR mutation could improve with specific approved treatments.
Informed Consent/Assent
+2 more
Exclusion Criteria
I cannot use CFTR modulators due to conditions like advanced cirrhosis or ESRD.
I am not taking any medications that interact badly with others.
You have smoked cigarettes within the last 6 months.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive off-label CFTR modulators such as Symdeko, Orkambi, or Ivacaftor based on their CFTR mutation response
32 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing Symdeko in patients with Cystic Fibrosis who have certain genetic mutations. It's designed to see if this medication can help even though it's not officially approved for these particular mutations.
3Treatment groups
Experimental Treatment
Group I: SymdekoExperimental Treatment1 Intervention
Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Symdeko, depending on the in vitro response pattern
Group II: OrkambiExperimental Treatment1 Intervention
Patients who have a mutation that responds to a CFTR corrector from in vitro study will be given Orkambi, depending on the in vitro response pattern
Group III: IvacaftorExperimental Treatment1 Intervention
Patients who have mutation response to a potentiator of CFTR function will be given Ivacaftor monotherapy.. Patients with a mutation equivalent to wild type will be given Ivacaftor.
Symdeko is already approved in United States, Canada, European Union for the following indications:
πΊπΈ Approved in United States as Symdeko for:
- Cystic fibrosis in people ages 12 and older with certain mutations in the CFTR gene
π¨π¦ Approved in Canada as Symdeko for:
- Cystic fibrosis in people with certain mutations in the CFTR gene
πͺπΊ Approved in European Union as Symkevi for:
- Cystic fibrosis in people with certain mutations in the CFTR gene
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Alabama at BirminghamBirmingham, AL
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Who Is Running the Clinical Trial?
University of Alabama at BirminghamLead Sponsor
References
Real-world data on the efficacy and safety of tezacaftor-ivacaftor in adults living with cystic fibrosis homozygous for F508del and heterozygous for F508del and a residual function mutation. [2023]To examine safety and efficacy of tezacaftor-ivacaftor (TEZ/IVA) in a real-life setting in adults living with cystic fibrosis.
Efficacy and safety of elexacaftor plus tezacaftor plus ivacaftor versus tezacaftor plus ivacaftor in people with cystic fibrosis homozygous for F508del-CFTR: a 24-week, multicentre, randomised, double-blind, active-controlled, phase 3b trial. [2022]Elexacaftor plus tezacaftor plus ivacaftor is a triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be generally safe and efficacious in people with cystic fibrosis aged 12 years or older with at least one F508del-CFTR allele. We aimed to assess the magnitude and durability of the clinical effects of this triple combination regimen in people with cystic fibrosis homozygous for the F508del-CFTR mutation.
Tezacaftor and ivacaftor for the treatment of cystic fibrosis. [2021]Introduction: Cystic fibrosis (CF) is a complex, multi-system, genetic disease affecting over 70,000 people worldwide. The underlying defect is a mutation in the CFTR gene. Dysfunctional CFTR protein results in abnormal anion movement across epithelial membranes in affected organs. There has been a paradigm shift in CF treatment over the last decade with the advent of CFTR modulation, treatments which target this underlying genetic defect and have the potential to change the course of CF clinical disease.Areas covered: Available CFTR modulators in current clinical practice are reviewed in this article, with a direct comparison and summary of relevant pivotal clinical trials. The approval of ivacaftor and subsequent development of lumacaftor and tezacaftor dual combinations represents an exciting development in CF management in recent years.Expert opinion: Tezacaftor/ivacaftor (tez/iva) appears to have a more favorable adverse event and drug-drug interaction profile than lumacaftor/ivacaftor. Tez/iva has been approved, alongside Phe508del, for a large number of 'residual function' CFTR mutations, with some based on response to in vitro culture. Dual therapy with tez/iva has paved the way for triple CFTR modulation currently in clinical trials with an ultimate view to provide modulation therapy to the majority of CF genotypes in the future.
Elexacaftor-Tezacaftor-Ivacaftor: The First Triple-Combination Cystic Fibrosis Transmembrane Conductance Regulator Modulating Therapy. [2020]Elexacaftor-tezacaftor-ivacaftor is a newly approved triple-combination cystic fibrosis transmembrane conductance regulator (CFTR) modulating therapy that contains 2 correctors and a potentiator of the CFTR channel. Its labeled indication for use is for persons 12 years of age and older with at least 1 F508del mutation for the CFTR gene. This drug combination provides potential therapy to many patients who had previously been excluded from CFTR modulation therapy due to the nature of their genetic mutations. The efficacy demonstrated in clinical trials surpasses the currently available therapies related to lung function, quality of life, sweat chloride reduction, and reducing exacerbations. The most common adverse events seen in clinical trials included rash and headache, and laboratory monitoring is recommended to evaluate liver function. Continued evaluation of patient data is needed to confirm its long-term safety and efficacy. Elexacaftor-tezacaftor-ivacaftor is a monumental and encouraging therapy for cystic fibrosis; however, approximately 10% of the CF population are not candidates for this or any other CFTR modulation therapy.
Real-life impact of highly effective CFTR modulator therapy in children with cystic fibrosis. [2023]Introduction: Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor/tezacaftor/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one F508del mutation. Objective: To assess the intermediate term effects of elexacaftor/tezacaftor/ivacaftor in children with cystic fibrosis in a real-world setting. Methods: We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor/tezacaftor/ivacaftor between 8/2020 and 10/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6 months after the start of elexacaftor/tezacaftor/ivacaftor respectively. Results: Elexacaftor/tezacaftor/ivacaftor was started in 22 children 6-11 years and in 24 children 12-17 years. Twenty-seven (59%) patients were homozygous for F508del (F/F) and 23 (50%) patients were transitioned from ivacaftor/lumacaftor (IVA/LUM) or tezacaftor/ivacaftor (TEZ/IVA) to elexacaftor/tezacaftor/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3 mmol/L (95% confidence interval: -65.0 to -53.7 mmol/L, p < 0.0001) under elexacaftor/tezacaftor/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA/LUM or TEZ/IVA to elexacaftor/tezacaftor/ivacaftor (-47.8 mmol/l; 95% confidence interval: -57.6 to -37.8 mmol/l, n = 14, p < 0.0001). Sweat chloride reduction was more marked in children with the F/F than in those with the F/MF genotype (69.4 vs 45.9 mmol/L, p < 0.0001). At 3 months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2-0.42, p < 0.0001) with no further increase at 6 months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV1) at 3 months follow-up increased by 11.4% (95% CI: 8.0-14.9, p < 0.0001) with no further significant change after 6 months. No significant differences were noted between the age groups. Children with the F/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F/F genotype. Adverse events led to elexacaftor/tezacaftor/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases. Conclusion: In a real-world setting, elexacaftor/tezacaftor/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3 months of elexacaftor/tezacaftor/ivacaftor therapy was sustained at 6 months follow-up.
Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events. [2022]Label="BACKGROUND">Increased rates of respiratory adverse events have been observed in people ≥12 years of age with cystic fibrosis homozygous for the Phe508del-CFTR mutation treated with lumacaftor/ivacaftor, particularly in those with percent predicted forced expiratory volume in 1 s (ppFEV1) of <40%. We evaluated the safety, tolerability, and efficacy of tezacaftor/ivacaftor in people with cystic fibrosis homozygous for Phe508del-CFTR who discontinued lumacaftor/ivacaftor due to treatment-related respiratory signs or symptoms.
Phase 1 Study to Assess the Safety and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor in Subjects Without Cystic Fibrosis With Moderate Hepatic Impairment. [2022]Elexacaftor/tezacaftor/ivacaftor is highly effective in treating people with cystic fibrosis (pwCF) who have β₯ 1 responsive mutation. Liver disease occurs in approximately 10%-20% of pwCF. The objective of this study was to assess the safety and pharmacokinetics of elexacaftor/tezacaftor/ivacaftor in people with moderate hepatic impairment, which is necessary to inform on its use and guide dosing recommendations.
If At First You Don't Succeed, Trikafta Again. [2022]Adverse reactions, including severe cutaneous reactions, to cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been described in the literature. Herein we present a drug eruption in response to elexacaftor/tezcaftor/ivacaftor (brand name, Trikafta) in a 7-year-old male with cystic fibrosis, followed by desensitization and successful continuation. A review of the literature outlining similar cases is provided. Attempting to mitigate and manage drug reactions to CFTR modulators is essential because they represent vital and irreplaceable therapies for individuals with cystic fibrosis (CF).
Patient perspectives following initiation of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis and advanced lung disease. [2022]Elexacaftor-tezacaftor-ivacaftor partially restores cystic fibrosis transmembrane conductance regulator function, and has been shown to induce significant clinical improvement in patients with at least one Phe508del allele. Yet little data exist on patient perspectives following elexacaftor-tezacaftor-ivacaftor initiation.
Elexacaftor/Tezacaftor/Ivacaftor as a Bridge to Lung Retransplant in a Recipient With Cystic Fibrosis. [2022]The triple-combination cystic fibrosis transmembrane conductance regulator modulator elexacaftor/- tezacaftor/ivacaftor is known to improve lung function and have extrapulmonary benefits in people with cystic fibrosis. However, there is limited evidence for its use in patients with cystic fibrosis after lung transplant, where the donor lung expresses normal levels of the cystic fibrosis transmembrane conductance regulator. We describe the use of elexacaftor/tezacaftor/ivacaftor as a bridge to potential lung retransplant in a 37-year-old man with cystic fibrosis and chronic lung allograft dysfunction. Although forced expiratory volume in 1 second did not improve, the patient had decreased sputum volume, no pulmonary exacerbations of cystic fibrosis, and no longer required continuous antibiotic therapy. Pancreatic function, revised Cystic Fibrosis Questionnaire scores, sinus symptoms, weight, and corticosteroid dependence significantly improved. There were no reported side effects attributable to elexacaftor/tezacaftor/ivacaftor. However, the patient exhibited declined renal function, which had been initially attributed to lability in cyclosporin levels but which were corrected after lithotripsy for renal calculi. Triple-combination modulators of the cystic fibrosis transmembrane conductance regulator may offer benefits to carefully selected individuals awaiting retransplant, balanced against the risk of worsened immunosuppressant level control.
Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations. [2021]Tezacaftor/ivacaftor is a CFTR modulator approved to treat people with cystic fibrosis (pwCF) who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function mutation (F/RF). This randomized, double-blind, placebo-controlled Phase 3 study evaluated the efficacy, safety, tolerability, and pharmacokinetics (PK) of tezacaftor/ivacaftor in participants β₯12 years of age heterozygous for the F508del-CFTR mutation and a minimal function mutation (F/MF), which produces no CFTR protein or a protein unresponsive to tezacaftor/ivacaftor in vitro.