A Phase 2, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of VX-561 in Subjects Aged 18 Years and Older With Cystic Fibrosis

Phase 2

Withdrawn

Conditions: Cystic fibrosis

Registration Number: NL-OMON47983

Lead Sponsor: Vertex Pharmaceuticals

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 2

Inclusion Criteria

1. Subject will sign and date an informed consent form (ICF)., 2. Willing and
able to comply with scheduled visits, treatment plan, study restrictions,
laboratory tests, contraceptive guidelines, and other study procedures., 3.
Subjects (males and females) aged 18 years or older on the date of informed
consent., 4. Receiving IVA treatment with no interruptions for at least 28 days
before screening., 5. Tolerating IVA therapy as judged by the investigator., 6.
Female subjects must have a negative pregnancy test at Screening., 7. Body
weight *35 kg., 8. Subjects must be able to produce a valid
(quantity-sufficient) sweat sample at screening. If the initial screening
collection results in insufficient sweat volume, then the sweat chloride
collection may be repeated., 9. Confirmed diagnosis of CF as determined by the
investigator., 10. Has 1 of the following mutations in their CF gene: G551D,
G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R. If the screening
CFTR genotype result is not received before randomization, a previous CFTR
genotype laboratory report may be used to establish eligibility. Subjects who
have been enrolled and whose screening genotype does not confirm study
eligibility must be discontinued from the study., 11. Subjects must have a
forced expiratory volume in 1 second (FEV1) *40% and *100% of predicted normal
for age, sex, and height (equations of the Global Lung Function Initiative
[GLI])8 at the Screening Visit. Spirometry measurements must meet American
Thoracic Society/European Respiratory Society criteria9 for acceptability and
repeatability., 12. Stable CF disease as judged by the investigator., 13.
Willing to remain on a stable CF treatment regimen (other than
protocol-specified changes in CFTR modulator regimen) through the Safety
Follow-up Visit.

Exclusion Criteria

1. 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., 2. History of clinically significant cirrhosis with
or without portal hypertension., 3. 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)10,11 for subjects *18 years of age, 4. An acute upper or lower
respiratory infection, pulmonary exacerbation, or changes in therapy (including
antibiotics) for sinopulmonary disease within 28 days before the first dose of
study drug., 5. Lung infection with organisms associated with a more rapid
decline in pulmonary status (e.g., 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 1 within the 6 months
before the date of informed consent., 6. An acute illness not related to CF
(e.g., gastroenteritis) within 14 days before the first dose of study drug., 7.
Standard 12-lead ECG demonstrating QTcF >450 msec at screening. If QTcF
exceeds 450 msec, the ECG will be repeated 2 more times, and the average of the
3 QTcF values will be used to determine the subject*s eligibility., 8. History
of solid organ or hematological transplantation., 9. History of alcohol or drug
abuse in the past year, including, but not limited to, cannabis, cocaine, and
opiates, as deemed by the investigator., 10. Ongoing or prior participation in
a study of an investigational treatment with the exception of the following:, *
Ongoing or prior participation in an investigational study of a Vertex CFTR
modulator. A washout period of 28 days must elapse before Day 1., * For
prospective subjects with ongoing or prior participation in all other
interventional studies, a washout period of 28 days or 5 terminal half-lives
(whichever is longer) must elapse before screening. The duration of the elapsed
time may be longer if required by local regulations., * Ongoing participation
in a noninterventional study (including observational studies and studies
requiring assessments without administration of study drug or assignment to
other interventions) is permitted., 11. Use of prohibited medications as
defined in the protocol, within the specified window before the first dose of
study drug., 12. Pregnant or nursing female subjects., 13. Subject, or close
relative of the subject, is the investigator or a subinvestigator, research
assistant, pharmac

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Endpoint<br /><br>* Absolute change in percent predicted forced expiratory volume in 1 second<br /><br>(ppFEV1) from baseline at Week 12</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary Endpoints<br /><br>* Absolute change in sweat chloride concentrations from baseline at Week 12<br /><br>* PK parameters of VX-561, IVA, and relevant metabolites<br /><br>* Safety and tolerability, based on the assessment of adverse events (AEs),<br /><br>laboratory test results, standard 12-lead ECGs, vital signs, and pulse oximetry</p><br>