Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: VX-121
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
Current Sponsor code: VX-121
Other descriptive name: VX-121
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject will sign and date an informed consent form (ICF). 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 3. Subjects (male and female) aged 18 years or older on the date of informed consent. 4. Female subjects must have a negative serum pregnancy test at the Screening Visit. 5. Body weight =35 kg. 6. Subjects must be able to produce a valid (quantity-sufficient) sweat sample at screening. If the initial screening collection results in insufficient sweat volume, then the sweat chloride collection may be repeated once. Subjects must have a sweat chloride value =60 mmol/L at screening or documented in the form of a laboratory report in the subject’s medical record. 7. Confirmed diagnosis of CF as determined by the investigator. 8. Subjects must have an eligible CFTR genotype as noted below. If the screening CFTR genotype result is not received before the Run-in Period (Part 2) or randomization (Parts 1 and 3), a previous CFTR genotype laboratory report may be used to establisheligibility. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility must be discontinued from the study • Parts 1 and 3: Heterozygous for F508del with a second CFTR allele carrying a mutation that does not produce a protein, or produces a protein that is not responsive to TEZ, IVA, or TEZ/IVA therapy • Part 2: Homozygous for F508del 9. Subjects must have a forced expiratory volume in 1 second (FEV1) =40% and =90% of predicted normal for age, sex, and height (equations of the Global Lung Function Initiative [GLI]) at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability. 10. Stable CF disease as judged by the investigator. 11. Willing to remain on a stable CF treatment regimen (other than protocol-specified changes in CFTR modulator regimen) through the Safety Follow-up Visit. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 108 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. 2. History of clinically significant cirrhosis with or without portal hypertension. 3. Risk factors for Torsade de Pointes and other ventricular arrhythmias, including but not limited to, history of any of the following: familial long QT syndrome, chronic hypokalemia, heart failure, left ventricular hypertrophy, chronic bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia (ventricular or atrial fibrillation), obesity, acute neurologic events (subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, or intracranial trauma), or autonomic neuropathy. 4. Any of the following abnormal laboratory values at screening: • Hemoglobin 450 msec at screening. If QTcF exceeds 450 msec, the ECG will be repeated 2 more times, and the average of the 3 QTcF values will be used to determine the subject’s eligibility. 9. History of solid organ or hematological transplantation. 10. History of alcohol or drug abuse in the past year, including, but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator. 11. Ongoing or prior participation in a study of an investigational treatment with the exception of the following: • Ongoing or prior participation in an investigational study of a Vertex CFTR modulator. A washout period of 28 days must elap
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 4 week; Main Objective: Parts 1 (Subjects with F/MF genotypes) and 2 (Optional; Subjects with the F/F genotype) • To evaluate the safety and tolerability of VX-121 in triple combination (TC) with tezacaftor (TEZ)/VX-561 (deuterated ivacaftor [IVA]) • To evaluate the efficacy of VX-121 in TC with TEZ/VX-561 Part 3 (Optional; Subjects with the F/MF genotype) • To evaluate the safety and tolerability of VX-121 in TC with TEZ/IVA • To evaluate the efficacy of VX-121 in TC with TEZ/IVA ; Secondary Objective: Parts 1 and 2 • To evaluate the pharmacodynamic (PD) effect of VX-121 in TC with TEZ/VX-561 • To evaluate the pharmacokinetics (PK) of VX-121 when administered in TC with TEZ/VX-561 • To evaluate the PK of TEZ, VX-561, and their respective metabolites when administered in TC with VX-121 Part 3 • To evaluate the PD effect of VX-121 in TC with TEZ/IVA • To evaluate the PK of VX-121 when administered in TC with TEZ/IVA • To evaluate the PK of TEZ, IVA, and their respective metabolites when administered in TC with VX-121 ; Primary end point(s): • Safety and tolerability, based on the assessment of adverse events (AEs), laboratory test results, standard 12-lead ECGs, vital signs, and spirometry • Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline through Day 29 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 4 weeks; Secondary end point(s): • Absolute change in sweat chloride concentrations from baseline through Day 29 • Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline at Day 29 • PK parameters of VX-121, TEZ, VX-561, IVA (Part 3), and relevant metabolites | — |
Countries
Germany, Netherlands, Portugal, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed