Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years
- Conditions
- Cystic FibrosisMedDRA version: 20.0Level: PTClassification code 10011762Term: Cystic fibrosisSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2020-002251-38-DE
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 70
1. Subject’s legally appointed and authorized representative will sign and date an informed consent form (ICF).
2. Subjects (males and females), 2 through 5 years of age, inclusive, on the date of informed consent (and assent, as applicable).
3. In Part A, subjects must weigh =14 kg at Day 1. In Part B, subjects must weigh =10 kg at the Screening Visit.
4. Confirmed diagnosis of CF as determined by the investigator.
5. In Part A, subjects who are homozygous for F508del (F/F genotype) or heterozygous for F508del and an MF mutation that is not responsive to IVA and TEZ/IVA (F/MF genotypes). In Part B, subjects who have at least 1 F508del mutation in the CFTR gene or an ELX/TEZ/IVA-responsive CFTR mutation.
• Genotype should be confirmed at the Screening Visit. This assessment does not need to be repeated for confirmed subjects in Part A who wish to participate in Part B.
• 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.
6. Subjects with stable CF disease at the start of the Treatment Period as deemed by the investigator.
7. Subjects who are willing to remain on a stable CF medication regimen (other than CFTR modulators) through Day 15 (Part A) or through Week 24 (Part B) or, if applicable, through the Safety Follow-up Visit.
8. As judged by the investigator, the parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions and the parent or legal guardian 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: 70
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
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
• Cancer
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, aspartate transaminase (AST), or alanine transaminase (ALT) =2 × upper limit of normal (ULN)
• Alkaline phosphatase (ALP) or gamma-glutamyl transferase (GGT) =3 × ULN
• Abnormal renal function defined as glomerular filtration rate =45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)8
4. An acute upper or lower respiratory infection, PEx, 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 with 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.
Note: Ongoing participation in a noninterventional study (including observational studies) is permitted.
8. Use of restricted medication within specified duration before the first dose of study drug as defined in Table 9-2.
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
10. Part B only: Elevated serum ALT or AST =3 × ULN or total bilirubin = 2 × ULN in the previous year.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: evaluate the safety and tolerability of ELX/TEZ/IVA;Secondary Objective: • To evaluate the PK of ELX, TEZ, and IVA<br>• To evaluate the pharmacodynamics (PD) of ELX/TEZ/IVA<br>• To evaluate the efficacy of ELX/TEZ/IVA;Primary end point(s): Safety and tolerability assessments as determined by AEs, clinical laboratory<br>values, standard 12-lead ECGs, vital signs, and pulse oximetry;Timepoint(s) of evaluation of this end point: From signing of ICF until the safety FU visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • PK parameters of ELX, TEZ, IVA, and relevant metabolites<br>• Absolute change in sweat chloride (SwCl) from baseline through Week 24<br>• Absolute change in lung clearance index (LCI)2.5 from baseline through<br>Week 24;Timepoint(s) of evaluation of this end point: From signing of ICF until the safety FU visit