A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
Condition: Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Fibrosis
Intervention: VX-152; TEZ/IVA; IVA; Placebo; Placebo
Intervention description: Tablet for oral administration.; Fixed-dose combination tablet for oral administration.; Tablet for oral administration.; Placebo matched to VX-152.; Placebo matched to VX-152/TEZ/IVA triple combination (TC).
Intervention MeSH terms: Ivacaftor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.