A Study to Evaluate Efficacy and Safety of VX-561 in Subjects Aged 18 Years and Older With Cystic Fibrosis

Phase 1

Conditions: Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
Cystic Fibrosis
MedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders

Registration Number: EUCTR2018-003970-28-GB

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 88

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 88
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site. However, an adult (aged 18 years or older) who is a relative of a study staff m

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: • To evaluate the efficacy of VX-561;Secondary Objective: • To evaluate the PD effect of VX-561<br>• To evaluate the pharmacokinetics (PK) of VX-561, IVA, and relevant metabolites<br>• To evaluate the safety and tolerability of VX-561;Primary end point(s): • Absolute change in ppFEV1 from baseline at Week 12;Timepoint(s) of evaluation of this end point: week 12

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: week 12;Secondary end point(s): • Absolute change in sweat chloride concentrations from baseline at Week 12<br>• PK parameters of VX-561, IVA, and relevant metabolites<br>• Safety and tolerability, based on the assessment of adverse events (AEs), laboratory test results, standard 12-lead ECGs, vital signs, and pulse oximetry

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