Cystic Fibrosis MedDRA version: 19.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy. If the CFTR screening genotype result is not received before randomization, a previous CFTR genotype laboratory report may be used to establish eligibility. Confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis (as documented in the subject’s medical record OR from sweat chloride test result obtained at the Screening, if subject does not have a sweat chloride test result in the medical record). FEV1 =40% and =90% of predicted normal for age, sex, and height at Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability. Stable CF disease as judged by the investigator. Willing to remain on a stable CF medication regimen through Week 12 or, if applicable, the Safety Follow-up Visit. Are the trial subjects under 18? yes Number of subjects for this age range: 150 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 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. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug). Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of VX-661 in combination with ivacaftor through Week 12 in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy (F508del/not responsive [NR]);Secondary Objective: To evaluate the safety of VX-661 in combination with ivacaftor and to investigate the pharmacokinetics (PK) of VX-661 and its metabolite M1-661, and ivacaftor and its metabolite M1-ivacaftor;Primary end point(s): Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline through Week 12.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Relative change in percent predicted FEV1 from baseline through Week 12 Absolute change in sweat chloride from baseline through Week 12 Absolute change in body mass index (BMI) from baseline at Week 12 Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline through Week 12 Number of pulmonary exacerbations through Week 12 Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values (i.e., hematology, coagulation studies, serum chemistry, vitamin levels, lipid panel, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry Time-to-first pulmonary exacerbation through Week 12 Absolute change in BMI z-score from baseline at Week 12 (in subjects <20 years old at time of screening) Absolute change in body weight from baseline at Week 12 PK parameters of VX-661, M1-661, ivacaftor, and M1 ivacaftor ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
Australia, Austria, Canada, France, Germany, Israel, Spain, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed