Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)
Brief Summary: This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).


Options:
A: Key Inclusion Criteria:

* Heterozygous for the F508del mutation (F/MF)
* Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

* Clinically significant cirrhosis with or without portal hypertension
* Lung infection with organisms associated with a more rapid decline in pulmonary status
* Solid organ or hematological transplantation

Other protocol defined Inclusion/Exclusion criteria may apply
B: Inclusion Criteria:

* CF as diagnosed by:

  1. Documented sweat chloride greater than or equal to 60 mEq/L by quantitative pilocarpine iontophoresis test; or
  2. Two well-characterized genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene; or
  3. Abnormal nasal potential difference with accompanying symptoms characteristic of CF.
* PA present in expectorated sputum or throat swab culture at Screening.
* Participants must have received three or more courses of TIS within the previous 12 months.
* Participants on chronic azithromycin must have had no change in regimen in the previous 3 months and must have had a need for TIS and/or additional antipseudomonal therapy since initiation of azithromycin.
* Forced expiratory volume in 1 second (FEV1) between (and including) 25% and 75% predicted at Screening.
* Ability to perform reproducible pulmonary function tests.
* Arterial oxygen saturation (SaO2) greater than or equal to 90% on room air at Screening.

Exclusion Criteria:

* Current use of oral corticosteroids in doses exceeding the equivalent of 10 mg prednisone a day or 20 mg prednisone every other day.
* History of sputum or throat culture swab yielding Burkholderia cepacia in the past 2 years.
* History of daily continuous oxygen supplementation or requirement for more than 2 liters/minute at night.
* Administration of any investigational drug or device within 28 days of Screening (Visit 1) or within 6 half-lives of the investigational drug (whichever was longer).
* Known local or systemic hypersensitivity to monobactam antibiotics.
* Inability to tolerate inhalation of a short acting Beta-2 agonist.
* Changes in antimicrobial, bronchodilator, anti-inflammatory, or corticosteroid medications within 7 days before Screening or between Screening and the next visit.
* Changes in physiotherapy technique or schedule within 7 days before Screening or between Screening and the next visit.
* History of lung transplantation.
* A chest X-ray indicating abnormal findings at Screening or within the previous 90 days.
* Abnormal renal or hepatic function or serum chemistry at Screening (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] greater than 5 times the upper limit of normal range; Creatinine greater than 2 times the upper limit of normal range).
* Positive pregnancy test at Screening.
* Female of childbearing potential who was lactating or in the opinion of the investigator was not practicing acceptable birth control.
* Any serious or active medical or psychiatric illness, which in the opinion of the investigator would have interfered with participant treatment, assessment, or compliance with the protocol.
C: Inclusion Criteria:

* Confirmed diagnosis of Cystic Fibrosis
* Age ≥12 years
* Forced expiratory volume in 1 second (FEV1) ≥ 35% predicted
* Access to the internet

Exclusion Criteria:

* Participation in another clinical trial up to 4 weeks prior to the first baseline visit
* Pregnancy/Breastfeeding
* Inability to exercise
* More than 4 hours of reported strenuous physical activities per week currently or up to 3 months prior to baseline measurements and not already planned within the coming 6 months.
* Unstable condition precluding exercise (major hemoptysis or pneumothorax within the last 3 months, acute exacerbation and iv-antibiotics during the last 4 weeks, planned surgery, listed for lung transplantation, major musculoskeletal injuries such as fractures or sprains during the last 2 months, others according to the impression of the doctor)
* Cardiac arrhythmias with exercise
* Requiring additional oxygen with exercise
* Recent diagnosis of diabetes 3 months prior to screening or at screening
* Recent changes in medication 1 month or less prior to screening (systemic steroids, ibuprofen, inhaled antibiotics, mannitol, DNAse, hypertonic saline)
* At least one G551D mutation and not on ivacaftor (VX770) yet but planned start or planned stop of ivacaftor during the trial
* Colonization with Burkholderia cenocepacia
D: Inclusion Criteria:

* CF diagnosis confirmed with sweat test, abnormal nasal potential difference and/or genetic testing
* Age 14 and older
* Able to perform spirometry
* Clinically stable without antibiotic treatment for a pulmonary exacerbation in the two weeks prior to the screening visit
* Forced expiratory volume in the first second (FEV1) greater than 25% of predicted at screening

Exclusion Criteria:

* History of solid organ transplant
* Participation in any interventional trial within the last 30 days
* Inability to speak and read the English language well enough to complete questionnaires
* Colonization with Burkholderia cepacia genomovar III within the last 24 months
* Currently receiving antimicrobial treatment specifically used to treat active non-tuberculosis mycobacterium
* Confirmed diagnosis of allergic bronchopulmonary aspergillosis (ABPA) as defined by the Cystic Fibrosis Foundation (CFF) guidance document that is being actively treated

Answer: A