A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group,
 multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple
 Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with
 cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function
 (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are
 homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene
 (F508del/F508del).
Inclusion Criteria:

 -  Willing and able to comply with scheduled visits, treatment pan, study restrictions,
 laboratory tests, contraceptive guidelines, and other study procedures.

 -  Body weight ≥35 kg.

 -  Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.

 -  Subjects must have an eligible CFTR genotype:

 -  Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation
 known or predicted not to respond to TEZ and/or IVA.

 -  Cohorts 2A, 2B: Homozygous for F508del.

 -  Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height
 at the Screening Visit.

 -  Stable CF disease as judged by the investigator.

 -  Willing to remain on a stable CF medication regimen through the planned end of
 treatment or if applicable the Safety Follow-up Visit.

 Exclusion Criteria:

 -  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.

 -  History of cirrhosis with portal hypertension.

 -  Risk factors for Torsade de Pointes.

 -  History of hemolysis.

 -  Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.

 -  Clinically significant abnormal laboratory values at screening.

 -  An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in
 therapy for pulmonary disease within 28 days before the first dose of study drug.

 -  Lung infection with organisms associated with a more rapid decline in pulmonary
 status.

 -  An acute illness not related to CF within 14 days before the first dose of study drug.

 -  A standard digital ECG demonstrating QTc >450 msec at screening.

 -  History of solid organ or hematological transplantation.

 -  History or evidence of cataract or lens opacity determined to be clinically
 significant by the ophthalmologist or optometrist, based on the ophthalmologic
 examination during the Screening Period.

 -  History of alcohol or drug abuse in the past year, including but not limited to,
 cannabis, cocaine, and opiates, as deemed by the investigator.

 -  Ongoing or prior participation in an investigational drug study with certain
 exceptions.

 -  Use of commercially available CFTR modulator within 14 days before screening (applies
 only to Cohorts 1A, 1B, and 1C).

 -  Pregnant or nursing females: Females of childbearing potential must have a negative
 pregnancy test at screening and Day 1.