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’s legally appointed and authorized representative will sign and date an informed consent form (ICF) and the subject will sign and date an assent form (if applicable). 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) will be between the ages of 6 and 11 years, inclusive, on the date(s) of informed consent (and assent, if applicable). 4. Subjects who weigh =15 kg without shoes at the Screening Visit. 5. Genotypes as presented in Appendix 1 of the Protocol. Genotype is to be confirmed during screening. If the CFTR screening genotype result is not received before enrollment, a previous CFTR genotype lab 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 as described in Section 10.7 of the Protocol. Note: Additional mutations may be evaluated and updates to approved mutations will be communicated to investigative sites through a memorandum. 6. A confirmed diagnosis of CF4 as determined by the following criteria: a. For subjects who are F508del homozygous: confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis (as documented in the subject’s medical record OR from the sweat chloride test result obtained at the Screening Visit). b. For subjects who are F508del heterozygous: • Confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis (as documented in the subject’s medical record [this value may be obtained from a record collected prior to use of Kalydeco] OR from the sweat chloride test result obtained at the Screening Visit); OR • If the sweat chloride value is <60 mmol/L, there must be documented evidence of chronic sinopulmonary disease4 and/or gastrointestinal disease consistent with a diagnosis of CF as judged by the principal investigator, manifest by at least 1 of the following: o Persistent colonization/infection, defined as =2 positive respiratory cultures within a 6 month period, with 1 or more typical CF pathogens (e.g., Staphylococcus aureus, Haemophilus influenzae, mucoid and nonmucoid Pseudomonas aeruginosa) o Chronic cough and sputum production o Persistent chest radiograph abnormalities consistent with CF pulmonary disease (e.g., bronchiectasis, atelectasis, infiltrates, hyperinflation) o Nasal polyps, chronic sinusitis as manifest by radiographic or computed tomographic abnormalities of the paranasal sinuses o Evidence of gastrointestinal disease consistent with the diagnosis of CF o Significant delays in growth and/or weight gain consistent with the diagnosis of CF 9. Subjects with ppFEV1 of =70 percentage points adjusted for age, sex, height, and ethnicity using the Global Lung Function Initiative (GLI) equation5 at the Screening Visit (Section 11.4.2 of the Protocol). 10. Subjects with a screening LCI2.5 result =7.5. 11. Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
Exclusion criteria
Exclusion criteria: 1. History of any comorbidity reviewed at the Screening Visit 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. For example, history of cirrhosis with portal hypertension and/or history of risk factors for Torsades de Pointes (e.g., familial long QT syndrome, hypokalemia, heart failure, left ventricular hypertrophy, bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia [ventricular and atrial fibrillation], obesity, acute neurologic events [subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, intracranial trauma], and autonomic neuropathy). 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 the Screening Visit: • Hemoglobin 450 msec at the Screening Visit. If QTc exceeds 450 msec at the Screening Visit, the ECG should be repeated 2 more times during the Screening Period, and the average of the 3 QTc values should be used to determine the subject's eligibility. 7. History of solid organ or hematological transplantation at the Screening Visit. 8. Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator that does not align with the following requirements: • A washout period of 30 days or 5 terminal half-lives of the previous investigational study drug, whichever is longer, must elapse before screening. o The duration of the elapsed time may be longer if required by local regulations.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of tezacaftor in combination with ivacaftor (TEZ/IVA) in subjects with cystic fibrosis (CF) aged 6 through 11 years, homozygous or heterozygous for F508del;Secondary Objective: To evaluate the safety of TEZ/IVA in subjects with CF aged 6 through 11 years, homozygous or heterozygous for F508del;Primary end point(s): Absolute change in lung clearance index2.5 (LCI2.5) from baseline through Week 8;Timepoint(s) of evaluation of this end point: From Baseline through week 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Absolute change from baseline in sweat chloride at Week 8 • Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline through Week 8 • Safety and tolerability as measured by adverse events (AEs), clinically significant changes in laboratory values (serum chemistry, hematology, coagulation studies, lipids, vitamin levels, and urinalysis), standard 12-lead ECGs, vital signs, pulse oximetry, serial lung function measurement, and ophthalmologic examinations. ; Timepoint(s) of evaluation of this end point: From Baseline through week 8. Safety and tolerability will be measured thorough the study. | — |
Countries
Australia, Belgium, Denmark, France, Germany, Ireland, Poland, Switzerland, United Kingdom
Contacts
Public ContactClinical Trials and Medical Info
Vertex Pharmaceuticals Incorporated
Outcome results
None listed