A
- Conditions
- Cystic FibrosisMedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2020-003170-44-IT
- Lead Sponsor
- VERTEX PHARMACEUTICALS INCORPORATED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
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 (F/MF genotypes).
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
(Section 9.9).
5. Forced expiratory volume in 1 second (FEV1) value >o= 30% of predicted mean for age, sex, and height (equations of the Global Lung Function
Initiative [GLI])9 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 199
mg/dL) or CFRD (defined as either fasting hyperglycemia [blood glucose level >126 mg/dL after an 8-hour fast] or 2-hour post-OGTT blood
glucose level >200 mg/dL).
Are the trial subjects under 18? yes
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 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20
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, or a first degree relative with Type 2 diabetes.
3. Duration of CFRD > o = 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 <10 g/dL
- Total bilirubin >o= 2 x upper limit of normal (ULN)
- Aspartate transaminase (AST), alanine transaminase (ALT), gammaglutamyl transferase (GGT), or alkaline phosphatase (ALP) >0=3 xULN
- Abnormal renal function defined as glomerular filtration rate 6. 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).
7. 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.
8. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug (Day 1).
9. Ongoing or prior participation in an investigational drug study (including studies investigating ELX with or without coadministration of
other study drugs) within 28 days of the Screening Visit.
- A washout period of 5 terminal half-lives of the previous investigational
study drug, or 28 days, whichever is longer, must elapse before the Screening Visit.
- The duration of the elapsed time may be longer if required by local
regulations.
10. Use of restricted medication (including antidiabetic medication other
than insulin, which must be at a dose no greater than 0.3 units/kg/day)
within specified duration before the first dose of study drug as defined in
Table 9-1.
11. BMI >o=30 kg/m2 at the Screening Visit.
12. Pregnant and breast-feeding females. All female subjects regardless
of childbearing potential status (Section 11.4.6) must have a negative
pregnancy test at the Screening Visit and the Day 1 Visit.
13. The subject or a close relative of the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effect of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor<br>(IVA) on glucose tolerance in CF subjects with impaired glucose<br>tolerance (IGT) or CF-related diabetes (CFRD);Secondary Objective: To evaluate the safety and tolerability of ELX/TEZ/IVA;Primary end point(s): Change from baseline in 2-hour blood glucose levels following an oral glucose tolerance test<br>(OGTT) to the average of Week 36 and Week 48;Timepoint(s) of evaluation of this end point: Week 36 and Week 48
- Secondary Outcome Measures
Name Time Method Secondary end point(s): -Proportion of subjects with improvement in dysglycemia categorization (CFRD, IGT, normal glucose tolerance [NGT]) at Week 48<br>-Safety and tolerability of ELX/TEZ/IVA based on adverse events (AEs), clinical laboratory values, ECGs, vital signs, and pulse oximetry;Timepoint(s) of evaluation of this end point: Week 48