A study in children aged 6 Through 11 Years With Cystic Fibrosis to assess the efficacy and safety of a combination of two experimental drugs
- Conditions
- Cystic FibrosisTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2015-000543-16-DE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- Subjects (males and females), will be between the ages of 6 and 11 years, inclusive, on the date of informed consent (and assent, if applicable).
- Subjects who weigh =15 kg without shoes at the Screening Visit.
- Subjects with confirmed diagnosis of CF at the Screening Visit. CF is defined as:
• 2 CF causing mutations (all as documented in the subject's medical record) AND
• chronic sinopulmonary disease OR gastrointestinal/nutritional abnormalities
- Subjects who are homozygous for the F508del CFTR mutation (genotype to be confirmed at the Screening Visit).
- Subjects with percent predicted FEV1 of =70 through =105 percentage points adjusted for age, sex, and height using the Wang equation at the Screening Visit.
- Subjects with a screening LCI 2.5 result greater than or equal to 7.5
- Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
- Subjects who are willing to remain on a stable CF medication regimen through Week 24 or, if applicable, through the Safety Follow up Visit.
- Subjects who are able to swallow tablets.
Are the trial subjects under 18? yes
Number of subjects for this age range: 200
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
- 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.
- 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).
- Any of the following abnormal laboratory values at the Screening Visit:
• Hemoglobin <10 g/dL
• Abnormal liver function defined as any 3 or more of the following:
• =3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
• =3 × ULN alanine aminotransferase (ALT)
• =3 × ULN gamma glutamyl transpeptidase
• =3 × ULN alkaline phosphatase
• ALT or AST >5 × ULN
• Total bilirubin >2 × ULN
• Abnormal renal function defined as glomerular filtration rate =45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)
- 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).
- A standard 12 lead ECG demonstrating QTc >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.
- History of solid organ or hematological transplantation at the Screening Visit.
- Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of the Screening Visit.
- Use of restricted medication or food within specified duration before the first dose of study drug
- History of cataract/lens opacity or evidence of cataract/lens opacity, as determined by the ophthalmologic examination at the Screening Visit. The Screening Visit ophthalmologic examination does not need to be repeated if there is documentation of an examination meeting protocol criteria that was conducted within 3 months before the Screening Visit. All subjects will have an eye exam performed by an ophthalmologist at the Screening Visit and at the Week 24 Visit OR the Week 28 Safety Follow up Visit
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 lumacaftor in combination with ivacaftor in subjects aged 6 Through 11 years with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene;Secondary Objective: - To evaluate the safety of lumacaftor in combination with ivacaftor<br>- To investigate the pharmacokinetics (PK) of lumacaftor and its metabolite (M28-lumacaftor) and ivacaftor and its metabolites (M1-ivacaftor and M6-ivacaftor);Primary end point(s): Absolute change in lung clearance index 2.5 (LCI2.5);Timepoint(s) of evaluation of this end point: From baseline through Week 24
- Secondary Outcome Measures
Name Time Method Secondary end point(s): - Average absolute change in sweat chloride from baseline at Day 15 and at Week 4<br>- Absolute change in body mass index (BMI) from baseline at Week 24<br>- Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score from baseline through Week 24<br>- Absolute change in LCI5.0 from baseline through Week 24<br>- Absolute change in sweat chloride from baseline at Week 24<br>- Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) from baseline through Week 24<br>- Relative change in ppFEV1 from baseline through Week 24<br>- Absolute change in BMI for age z score from baseline at Week 24<br>- Absolute change in weight from baseline at Week 24<br>- Absolute change in weight for age z score from baseline at Week 24<br><br><br>;Timepoint(s) of evaluation of this end point: Baseline through Week 24 or Baseline at week 24