Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Vertex Pharmaceuticals Incorporated
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject (or his or her legally appointed and authorized representative) will sign and date an informed consent form (ICF), and 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.Subjects (male and female) 6 through 11 years of age, inclusive, on the date of informed consent. 4.Subjects who weigh =15 kg without shoes at the Screening Visit. 5.Confirmed diagnosis of CF as determined by the investigator. 6.Subjects heterozygous for F508del and an MF mutation that is not responsive to IVA and TEZ/IVA (F/MF genotypes, Protocol Appendix A). •Genotype should be confirmed at the Screening Visit. •If the screening CFTR genotype result is not received before the first dose of study drug, 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 (Protocol Section 9.9). 7.Subjects with FEV1 value =70% of predicted normal for age, sex, and height using equations of the Global Lung Function Initiative (GLI)11 as determined by spirometry at screening (Protocol Section 11.3.1). 8.Subjects with a screening LCI2.5 result = 7.5 (Protocol Section 11.3.2). 9.Subjects with stable CF disease at the start of the Treatment Period as deemed by the investigator. 10.Subjects who are willing to remain on a stable CF medication regimen (other than CFTR modulators) through Week 24 or, if applicable, through the Safety Follow up Visit 11.Subjects who are able to swallow tablets. 12. As deemed by the investigator, the subject’s legally appointed and authorized representative (e.g., parent or legal guardian) AND the subject must be able to understand protocol requirements, restrictions, and instructions. The subject’s legally appointed and authorized representative should be able to ensure that the subject will comply with and is likely to complete the study as planned. Are the trial subjects under 18? yes Number of subjects for this age range: 108 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 liver 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 with no recurrence for the last 5 years) 2.Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (as deemed by the investigator). 3.Any of the following abnormal laboratory values at screening: •Hemoglobin <10 g/dL •Total bilirubin =2 × 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 =45?mL/min/1.73?m2 (calculated by the Counahan-Barratt equation)12 4.An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug). 5.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 one 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 (Day 1). 7.Ongoing or prior participation in an investigational drug study (including studies investigating ELX with or without coadministration of other study drugs) within 28 days of the Screening Visit. •A washout period of 5 terminal half lives of the previous investigational study drug, or 28 days, whichever is longer, must elapse before the Screening Visit. •The duration of the elapsed time may be longer if required by local regulations. 8.Use of restricted medication within specified duration before the first dose of study drug as defined in Protocol Table 9 2. 9.Pregnant and breast-feeding females. Female subjects of childbearing potential status (Protocol Section 11.5.6) must have a negative pregnancy test at the Screening Visit and the Day 1 Visit. 10.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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of elexacaftor (VX-445; ELX)/tezacaftor (TEZ)/ivacaftor (IVA) in subjects 6 through 11 years old with cystic fibrosis (CF), heterozygous for F508del and a minimal function (MF) mutation (F/MF);Secondary Objective: •To evaluate the pharmacodynamics (PD) of ELX/TEZ/IVA •To evaluate the safety of ELX/TEZ/IVA ;Primary end point(s): Absolute change in lung clearance index 2.5 (LCI2.5) from baseline through Week 24;Timepoint(s) of evaluation of this end point: From Baseline at each post-baseline visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Absolute change in sweat chloride (SwCl) from baseline through Week 24 •Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard 12 lead electrocardiograms (ECGs), vital signs, and pulse oximetry ;Timepoint(s) of evaluation of this end point: From Baseline at each post-baseline visit. | — |
Countries
Australia, Canada, Denmark, France, Germany, Israel, Netherlands, Spain, Switzerland, United Kingdom
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed