A study to assess the safety and pharmacodynamics of long-term ivacaftor treatment in children less than 24 months of age with cystic fibrosis (a rare hereditary disease that affects the lungs, digestive system and other organs).
- Conditions
- Cystic FibrosisMedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2017-001379-21-DE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 75
Ivacaftor Arm: Subjects From Study 124 Part B
1. Subjects transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B
Added guidance:
- Subjects who had a study drug interruption at the last scheduled visit of Study 124 Part B,
subjects who required study drug interruption that was to be continued or initiated at Day 1 in
Study 126, or subjects who resumed study drug in Study 124 Part B after a study drug
interruption due to elevated transaminases but who did not complete at least 4 weeks of
rechallenge with study drug (due to the timing of the rechallenge versus the time remaining
in Study 124 Part B) must meet eligibility criteria and have received approval from the
Vertex medical monitor.
2. For Gap Transition subjects: hematology and serum chemistry results at baseline with no
clinically significant abnormalities that would confound the study assessments or pose an
additional risk to administering ivacaftor to the study subject, as judged by the investigator.
3. As judged by the investigator, parent or legal guardian must be able to understand protocol
requirements, restrictions, and instructions; and must sign the informed consent form (ICF).
Ivacaftor Arm: Subjects Not From Study 124 Part B
1. Age <24 months at the Day 1 Visit
2. Confirmed diagnosis of CF, defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis or 2 CF-causing mutations
- If the results of the sweat chloride and/or the genotype test are documented in the subject’s
medical record, and the historic genotype result is approved by the Vertex medical monitor, the tests do not need to be performed at screening. A sweat chloride test must be performed if the sweat chloride value is not available in the subject’s medical records and the value is needed to establish eligibility.
3. An ivacaftor-responsive CFTR mutation on at least 1 allele. Subjects will be eligible in countries/regions where ivacaftor is approved for use in subjects 2 years of age and older.
- If a genotype test has been performed previously and is documented in the subject’s medical record, the subject's eligibility must be approved by the Vertex medical monitor. If a historic
genotype result is not available at screening or if the historic genotype result is not approved by the Vertex medical monitor, the subject will undergo CFTR genotype screening and the results must be reviewed before the first dose of ivacaftor. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility will not receive study drug.
4. Hematology, serum chemistry, and vital signs results have no clinically significant abnormalities that would confound the study assessments, as judged by the investigator.
5. Weight at screening must be within the weight limites as defined for the study drug dose levels or according to the dosing guidelines identified in the 'Justification for Dose Selection' memorandum effective at the time a subject is screened
6. For subjects <3 months of age only, gestational age =38 weeks.
7. As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF.
Observational Arm
1. Completed ivacaftor treatment in Study 124 Part B and elected not to enroll in the ivacaftor arm of Study 126, or received at least 1 dose of ivacaftor and prematurely discontinued ivacaftor treatment in Study 124 Part B and received a
Ivacaftor Arm: Subjects From Study 124 Part B
1. History of any illness or condition that, in the opinion of the investigator, might confound the
results of the study or pose an additional risk in administering ivacaftor to the subject.
Examples of subjects who may not be eligible include
- subjects with a history of allergy or hypersensitivity to the study drug; and
- subjects with severe or life-threatening reactions to the study drug in Study 124.
2. Subjects receiving commercially available ivacaftor treatment
Ivacaftor Arm: Subjects Not From Study 124 Part B
1. History of any illness or condition that, in the opinion of the investigator, might confound the
results of the study or pose an additional risk in administering ivacaftor to the subject
2. An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks of Day 1
3. Known colonization with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at screening. A subject is excluded if they have a positive culture of one of these organisms.
4. Abnormal liver function at screening or any prior history of clinically relevant elevated (>2 × upper limit of normal [ULN]) serum aspartate transaminase (AST), serum alanine transaminase (ALT), or bilirubin (excluding newborn hyperbilirubinemia, e.g., physiologic jaundice or breastmilk jaundice of the newborn)
5. Hemoglobin <9.5 g/dL at screening
6. History of solid organ or hematological transplantation
7. Any clinically significant non-CF-related” illness within 2 weeks of Day 1. Illness” is defined as an acute (serious or nonserious) condition (e.g., gastroenteritis)
8. Use of any moderate or strong inducers or inhibitors of cCYP3A within 2 weeks of Day 1
9. Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer or as determined by the local requirements) before screening. Note: Participation in a noninterventional study (including observational studies, registry studies, and studies requiring blood collections without administration of study drug) is permitted.
10. Chronic kidney disease of Stage 3 or above
11. Unable to undergo an adequate slit-lamp examination at screening
12. Presence of a lens opacity or cataract identified at the screening OE (excluding those
considered congenital and nonprogressive, such as a suture cataract)
Observational arm
1. Receiving ivacaftor treatment
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