A study to evaluate the safety and efficacy of VX-445 / Tezacaftor / Ivacaftor in patients suffering from Cystic Fibrosis

Phase 1

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

Registration Number: EUCTR2019-001735-31-BE

Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 158

Inclusion Criteria

1. Subject (or his or her legally appointed and authorized representative) will sign and date an informed consent form (ICF), and, when appropriate, an assent form.
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
3. Age 12 years or older, on the date of informed consent.
4. Confirmed diagnosis of CF as determined by the investigator.
5. Subject has the F/F genotype. Note: If the screening CFTR genotype result is not received before Day -28, a previous CFTR genotype laboratory report may be used to establish eligibility to enter the Run-in Period. Subjects who have been enrolled and whose screening genotype is not confirmed to be F/F must be discontinued from the study.
6. Forced expiratory volume in 1 second (FEV1) value =40% and =90% of predicted mean for age, sex, and height (equations of the Global Lung Function Initiative [GLI])11 at the Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria12 for acceptability and repeatability.
7. Stable CF disease as judged by the investigator.
8. Willing to remain on a stable CF treatment regimen through completion of study participation.

Are the trial subjects under 18? yes
Number of subjects for this age range: 32
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 126
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. History of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This includes, but is not limited to, the following:
• Clinically significant cirrhosis with or without portal hypertension.
• Solid organ or hematological transplantation.
• Alcohol or drug abuse in the past year, including, but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
• Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 having occurred more than 5 years before screening with no recurrence for the last 5 years).
2. 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)13, 14 for subjects =18 years of age and =45 mL/min/1.73 m2 (calculated by the Counahan Barratt equation)15 for subjects aged 12 to 17 years (inclusive)
3. An acute upper or lower respiratory infection, pulmonary exacerbation(s) (PEx), or changes in therapy (including antibiotics) for sinopulmonary disease within 28 days before the first dose of TEZ/IVA in the Run-in Period (Day 28).
4. Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, 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.
5. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of TEZ/IVA in the Run-in Period (Day 28).
6. Ongoing or prior participation in a study of an investigational treatment other than a Vertex CFTR modulator within 28 days or 5 terminal half lives (whichever is longer) before screening. The duration of the elapsed time may be longer if required by local regulations.
7. Use of prohibited medications as defined in Table 9 2, within the specified window before the first dose of TEZ/IVA in the Run-in Period (Day 28).
8. Pregnant or nursing females. All female subjects must have a negative pregnancy test at Screening/Day -56 (serum test) and TEZ/IVA Run-in Period/Day -28 (urine test).
9. The subject or a 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 member may be enrolled in the study provided that
• the adult lives independently of a

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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