A Phase 3b Open-label Study to Assess the Effect of Elexacaftor/Tezacaftor/Ivacaftor on Glucose Tolerance in Cystic Fibrosis Subjects with Abnormal Glucose Metabolism

Phase 3

Completed

Conditions: Cystic Fibrosis
10038686

Registration Number: NL-OMON52358

Lead Sponsor: Vertex Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 8

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 <200 mg/dL [>=7.77
to <11.10 mmol/L]) or CFRD (defined as either fasting hyperglycemia [blood
glucose level >=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

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 <10 g/dL
• Total bilirubin >=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 <=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 <18 years of age
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.
11. BMI >=30 kg/m2

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change from baseline in 2-hour blood glucose levels following an oral glucose<br /><br>tolerance test (OGTT) to the average of Week 36 and Week 48</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Proportion of subjects with improvement in dysglycemia categorization (CFRD,<br /><br>IGT, normal glucose tolerance [NGT]) at Week 48<br /><br>• Safety and tolerability of ELX/TEZ/IVA based on adverse events (AEs),<br /><br>clinical laboratory values, ECGs, vital signs, and pulse oximetry</p><br>