Cystic Fibrosis MedDRA version: 20.0 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: Part A Subjects entering the Treatment Cohort must meet all of the following criteria: • Elect to enroll in the Treatment Cohort. • Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109), study drug treatment and the Safety Follow up Visit for subjects from Study 111 or study drug treatment and follow-up as specified in other Vertex studies investigating VX-661 in combination with ivacaftor • Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit. Subjects re-enrolling in the treatment cohort must meet all the following criteria: • Previously received at least 4 weeks of study drug before discontinuing Study 110 to participate in another qualified Vertex study • Completed the last required visit of another qualified Vertex study before or during the returning visit Part A in Study 110 • Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit of Part A • Subjects who discontinue Study 110 more than once to participate in another qualified Vertex study may not re-enroll in Part A a second time Subjects entering the Part A Observational Cohort must meet the following criteria: • <18 years of age (age on the date of informed consent/assent in the parent study) • Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109), study drug treatment and the Safety Follow up Visit for subjects from Study 111 or study drug treatment and follow-up as specified in other Vertex studies investigating VX-661 in combination with ivacaftor, but do not elect to enroll in the Study 110 Treatment Cohort; or • Received at least 4 weeks of study drug treatment in a parent study, but do not meet eligibility criteria for enrollment into the Part A Treatment Cohort. Part B • Completed study drug treatment during the Treatment Period in Part A of VX14 661 110, Studies VX15 661 112 or VX16 661 114, or other eligible Vertex studies • For subjects in the middle of an approved study drug interruption at the end of the Parent study or Part A, or who re-started study drug after an interruption <4 weeks before the end of the Parent study or Part A, criteria for study drug resumption must be met and safety monitoring following resumption or rechallenge must be performed • Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit Subjects re enrolling in Part B must meet all of the following criteria • Previously received at least 4 weeks of study drug before discontinuing Study VX14 661 110 to participate in another qualified Vertex study • Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B • Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B. Part C Subjects who meet all of the following inclusion criteria will be eligible for Part C. • Signed and dated an ICF, and where appropriate, signed and dated an assent form. • Did not withdraw consent from Part B of Study VX14-661-110. • Able to understand and comply with protocol requirements, restrictions, and instructions, and likely to complete the study as planned, as judged by the investigator and Vertex, based in part on study compliance in the parent study and Study VX14-661-110 (Part A and B). • Completed study drug treatment during the Treatment Period
Exclusion criteria
Exclusion criteria: Part A Treatment Cohort: • 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. • Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit (and at Returning Visit for subjects who re-enroll) and before receiving the first dose of study drug. • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. • History of drug intolerance in the parent study or other qualified Vertex Study that would pose an additional risk to the subject. • History of poor compliance with study drug and/or procedures in the parent study or other qualified Vertex Study as deemed by the investigator. • Participation in an investigational drug trial other than Studies 103, 106, 107, 108, 109, 111, other Vertex studies investigating VX-661 in combination with ivacaftor, or other qualified study, or use of a commercially available CFTR modulator (e.g., Kalydeco). • Previous re-enrollment in the Part A Treatment Cohort of Study 110, after participating in other qualified Vertex studies. Part B • 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. • Pregnant and nursing females • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements • Subjects who permanently discontinue study drug treatment during the parent study or Part A • History of drug intolerance in the parent study, Part A of study VX14-661-110, or other qualified Vertex study that would pose an additional risk to the subject in the opinion of investigator or Vertex • History of poor compliance with study drug and/or procedures in the parent study, Part A of Study VX14-661-110, or other qualified Vertex study as deemed by the investigator • Participation in an investigational drug trial (other than Studies VX13 661 103, VX14 661 106, VX14 661 107, VX14 661 108, VX14 661 109, VX14 661 111, VX15 661 112, VX16 661 114, Part A of Study VX14-661-110, or other eligible Vertex studies investigating VX 661 in combination with ivacaftor) or use of a commercially available CFTR modulator (e.g., Kalydeco) • Discontinued Study VX14 661 110 (either Part A or Part B) more than once to participate in another qualified Vertex study. Part C Subjects who meet any of the following exclusion criteria will NOT be eligible for this study. • 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. For example: • History of cirrhosis with portal hypertension, and/or history of risk factors for Torsade de Pointes (e.g., familial long QT syndrome, hypokalemia, heart failure, left ventricular hypertrophy, bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia [ventricular and atrial fibrillation], obesity, acute neurologic events [subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, and intracranial trauma], and autonomic neuropathy) • Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit of Part C and before receiving the first dose of study drug in Part C. • Sexua
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A To evaluate the long-term safety and tolerability of VX-661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation who are in the Treatment Cohort. Part B and Part C Not applicable;Secondary Objective: Treatment Cohort Part A To evaluate the long-term efficacy of VX-661 in combination with ivacaftor for subjects in the Treatment Cohort. Part B • To evaluate the long-term safety, tolerability, and efficacy of VX 661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation. Part C • To evaluate the long-term safety and tolerability of VX-661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation Observational Cohort (Part A only) • To evaluate the post-treatment safety of VX-661 in combination with ivacaftor for subjects in the Observational Cohort ;Primary end point(s): Treatment Cohort: Part A Safety and tolerability of long-term treatment of VX-661 in combination with ivacaftor based on adverse events (AEs), ophthalmologic examinations (subjects <18 years of age, clinical laboratory values (serum chemistry, hematology, coagulation, lipids, vitamins, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry ;Timepoint(s) of evaluation of this end point: 96 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Through 100 weeks (Week 24 for PK endpoint);Secondary end point(s): Treatment Cohort Part A • Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) • Relative change from baseline in ppFEV1 • Number of pulmonary exacerbations • Absolute change from baseline in body mass index (BMI) • Absolute change from baseline in BMI z score for subjects aged <20 years • Absolute change from baseline in Cystic Fibrosis Questionnaire–Revised (CFQ R) respiratory domain score • Absolute change from baseline in body weight • Absolute change from baseline in body weight z-score for subjects aged <20 years • Absolute change from baseline in height z-score for subjects aged <20 years • Time to first pulmonary exacerbation, • Pharmacokinetic (PK) parameters of VX 661, a VX-661 metabolite (M1 661), ivacaftor, and an ivacaftor metabolite (M1 ivacaftor) Part B The following safety endpoints will be analyzed: • AEs • Ophthalmologic examaminations (subjects <18 years of age [age on the date of informed consent/assent in the parent study]) • Serum liver function tests (LFTs) The following efficacy endpoints will be analyzed: • Absolute change from baseline in ppFEV1 • Absolute change from baseline in BMI • Absolute change from baseline in BMI z-score (for subjects aged <20 years) • Number of pulmonary exacerbations Part C The following safety endpoints will be analyzed: • AEs • Ophthalmologic examinations (for subjects <18 years of age [age on date of informed consent/assent in the parent study]) • Serum liver function tests (LFTs) Observational Cohort (Part A only) • Safety, as determined by related serious adverse events (SAEs) | — |
Countries
Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed