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-659/Tezacaftor/Ivacaftor
Product Code: VX-659/TEZ/IVA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: VX-659
Current Sponsor code: VX-659
Other descriptive name: VX-659
C
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject (or his or her legally appointed and authorized representative) will sign and date an informed consent form (ICF), and, when appropriate, an assent form. 2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures. 3. Age 12 years or older, on the date of informed consent. 4. Confirmed diagnosis of CF as determined by the investigator. 5. Heterozygous for F508del and an MF mutation. If the screening CFTR genotype result is not received before randomization, a previous CFTR genotype laboratory report may be used to establish eligibility. Subjects who have been randomized and whose screening genotype does not confirm study eligibility must be discontinued from the study. 6. Forced expiratory volume in 1 second (FEV1) value =40% and =90% of predicted mean 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. 7. Stable CF disease as judged by the investigator. 8. Willing to remain on a stable CF treatment regimen through completion of study participation. Are the trial subjects under 18? yes Number of subjects for this age range: 120 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 240 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 illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This includes, but is not limited to, the following: • Clinically significant cirrhosis with or without portal hypertension • Solid organ or hematological transplantation. • Alcohol or drug abuse in the past year, including, but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator. • Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years) 2. Any of the following abnormal laboratory values at screening: • Hemoglobin <10 g/dL • Total bilirubin =2 × ULN • Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) =3 × ULN • Abnormal renal function defined as glomerular filtration rate =50 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease Study Equation) for subjects =18 years of age and =45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation) for subjects aged 12 to 17 years (inclusive) 3. An acute upper or lower respiratory infection, PEx, or changes in therapy (including antibiotics) for sinopulmonary disease within 28 days before the first dose of study drug (Day 1). 4. Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus). For subjects who have had a history of a positive culture, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms: • The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent. • The subject has had at least 2 respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent. 5. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug (Day 1). 6. Ongoing or prior participation in a study of an investigational treatment within 28 days or 5 terminal half-lives (whichever is longer) before screening. The duration of the elapsed time may be longer if required by local regulations. 7. Use of prohibited medications, within the specified window before the first dose of study drug (Day 1). 8. Pregnant or nursing females. Females of childbearing potential must have a negative pregnancy test at screening (serum test) and Day 1 (urine test). 9. The subject or a close relative of the subject is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site. However, an adult (aged 18 years or older) who is a relative of a study staff member may be randomized in the study provided that • the adult lives independently of and does not reside with the study staff member, and • the adult participates in the study at a site other than the site at which the family member is employed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects);Secondary Objective: • To evaluate the safety of VX-659 in TC with TEZ and IVA • To evaluate the pharmacodynamics (PD) of VX-659 in TC with TEZ and IVA • To evaluate the pharmacokinetics (PK) of VX-659, TEZ, and IVA when administered in TC;Primary end point(s): Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline through Week 24;Timepoint(s) of evaluation of this end point: At Week 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Absolute change in ppFEV1 from baseline at Week 4 2. Number of pulmonary exacerbations (PEx) through Week 24 3. Absolute change in SwCl from baseline through Week 24 4. Absolute change in Cystic Fibrosis Questionnaire - Revised (CFQ-R) respiratory domain score from baseline through Week 24 5. Absolute change in body mass index (BMI) from baseline at Week 24 6. Absolute change in SwCl from baseline at Week 4 7. Absolute change in CFQ-R respiratory domain score from baseline at Week 4 8. Time-to-first PEx through Week 24 9. Absolute change in BMI z-score from baseline at Week 24 10. Absolute change in body weight from baseline at Week 24 11. Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry 12. PK parameters of VX-659, TEZ, M1-TEZ, and IVA;Timepoint(s) of evaluation of this end point: 1. At Week 24 2. Through Week 24 3. Through Week 24 4. Through Week 24 5. At Week 24 6. At Week 4 7. At Week 4 8. Through Week 24 9. At Week 24 10. At Week 24 11. Day 1, 15, Weeks 4,8, 12, 16, 24, ETT Visit, Safety Follow up Visit 12. Day 1, Weeks 4, 8, 12, 16, ETT Visit | — |
Countries
Australia, Canada, Denmark, Germany, Ireland, Israel, Norway, Poland, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed