Cystic Fibrosis
Conditions
Interventions
Active substance: ELX (VX-445)/TEZ (VX-661)/IVA (VX-770)
Activity: CFTR correctors (ELX and TEZ) and potentiator (IVA)
Strength and route of administration: ELX 100-mg/TEZ 50-mg/IVA 75-mg fixed dose
Sponsors
Vertex Pharmaceuticals
Eligibility
Age
12 Years to 64 Years
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. Subjects (male and female) 12 years of age or older on the date of informed consent. 4. Subjects heterozygous for F508del and an MF mutation. a. Genotype should be confirmed at the Screening Visit. b. If the screening CFTR genotype result is not received before the first dose of study drug, a previous CFTR genotype laboratory report may be used to establish eligibility. c. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility must be discontinued from the study. 5. Forced expiratory volume in 1 second (FEV1) value >=30% 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) and stable CF disease as judged by the investigator. 6. Willing to remain on a stable CF treatment regimen (other than CFTR modulators) through completion of study participation. 7. Abnormal glucose tolerance as determined by an OGTT, classified as either IGT (defined as 2-hour post-OGTT blood glucose level >= 140 to =7.77 to =126 mg/dL (>=7.00 mmol/L) after an 8-hour fast] or 2-hour post-OGTT blood glucose level >=200 mg/dL [>=11.10 mmol/L]).
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 liver 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. Type 1 or Type 2 diabetes 3. Duration of CFRD >=5 years. 4. Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (as deemed by the investigator). 5. Any of the following abnormal laboratory values at screening: • Hemoglobin =2 × upper limit of normal (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 =18 years of age and =30 kg/m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in 2-hour blood glucose levels following an oral glucose tolerance test (OGTT) to the average of Week 36 and Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| • Proportion of subjects with improvement in dysglycemia categorization (CFRD, IGT, normal glucose tolerance [NGT]) at Week 48 • Safety and tolerability of ELX/TEZ/IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry | — |
Countries
Netherlands
Outcome results
None listed