VX15-809-110

Principal Investigator: Fadi Asfour
Keywords: cystic , Fibrosis , CF , Ivacaftor Department: Pediatric Pulmonology
IRB Number: 00083518 Co Investigator:  
Specialty: Pediatric Pulmonary Care
Sub Specialties: Cystic Fibrosis
Recruitment Status: Recruiting

Contact Information

Jane Vroom
jane.vroom@hsc.utah.edu
8015877458

Brief Summary

Vertex has established efficacy, safety, and pharmacokinetics (PK) profiles for lumacaftor and ivacaftor combination therapy in subjects 12 years of age and older, who are homozygous for the F508del-CFTR mutation (Studies VX12-809-103 [Study 103] and VX12-809-104 [Study 104]). In addition, preliminary safety and PK profiles for lumacaftor and ivacaftor combination therapy have been established in subjects 6 through 11 years of age, who are homozygous for the F508del-CFTR mutation (Study VX13-809-011 [Study 011] Part A). Ongoing Studies 011 Part B and VX14-809-109 [Study 109] are designed to obtain PK, safety, tolerability, pharmacodynamic (PD), and efficacy (Study 109 only) information to support an expanded indication for lumacaftor and ivacaftor combination therapy in the pediatric population (subjects 6 through 11 years of age, inclusive, who are homozygous for the F508del-CFTR mutation).

The long-term safety of lumacaftor in combination with ivacaftor has not yet been evaluated in subjects aged 6 through 11 years. Therefore, the primary objective of this study is to evaluate the long-term safety and tolerability of lumacaftor in combination with ivacaftor in subjects aged 6 years and older with CF, homozygous for the F508del-CFTR mutation.

Inclusion Criteria

1. Subject’s legally appointed and authorized representative (e.g., parent or legal guardian) will sign and date an ICF and the subject will sign and date an assent form (if applicable).

2. Subjects entering the Treatment Cohort must meet both of the following criteria: Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow-up in Study 011B (NOTE: the last dose of study drug is the evening dose administered the day before the Week 24 Visit in Study 109 or Study 011B)

o Subjects who had study drug interruptions, but completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B are eligible (this is Day 1 of Study 110 for subjects at Study 110 active sites). Subjects who are not taking study drug at the end of the Treatment Period (NOTE: subjects from Study 011B have a planned Washout Period from Week 24 to Week 26 and must still complete the Week 26 Safety Follow-up), including subjects who require study drug interruption to be either continued or initiated at Day 1 in Study 110, must have received Vertex approval for enrollment in the Treatment Cohort.

Elect to enroll in the Treatment Cohort

NOTE: Subjects who prematurely discontinued study drug treatment are not eligible for enrollment in the Treatment Cohort.

Subjects entering the Observational Cohort must meet 1 of the following criteria:

Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow-up in Study 011B (NOTE: the last dose of study drug is the evening dose administered the day before the Week 24 Visit in Study 109 or Study 011B), but do not elect to enroll in the Treatment Cohort

Subjects who received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B (this is Day 1 of Study 110 for subjects at Study 110 active sites) but are not taking study drug at the end of the Treatment Period (NOTE: subjects from Study 011B have a planned Washout Period from Week 24 to Week 26 and must still complete the Week 26 Safety Follow-up) because of a drug interruption and did not receive Vertex approval for enrollment into the Treatment Cohort (or elect not to enroll in the Treatment Cohort).

Subjects who permanently discontinued study drug after receiving at least 4 weeks of study drug and remained in the study from the time of discontinuation of study drug treatment through the Week 24 Visit in Study 109 or the Week 26 Visit of Study 011B.

3. Subjects who are willing to remain on a stable CF medication regimen through the Safety Follow-up Visit (Treatment Cohort only).

4. 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.

 

Exclusion Criteria

Subjects who meet any of the following exclusion criteria will not be eligible.

1. History of any comorbidity or laboratory abnormality 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 (e.g., cirrhosis with portal hypertension).

2. Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit before receiving the first dose of study drug.

3. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.

4. History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor. Examples of subjects who may not be eligible for the treatment cohort include (but are not limited to) the following:

Subjects with a history of allergy or hypersensitivity to the study drug

Liver function test (LFT) abnormality during study drug treatment in the previous study (Study 109 or Study 011B) for which a clear cause was not identified:

o Abnormal liver function defined as any 2 or more of the following:

  a. ≥3 × upper limit of normal (ULN) aspartate aminotransferase (AST)

  b. ≥ × ULN alanine aminotransferase (ALT)

  c. ≥ × ULN gamma-glutamyl transpeptidase

  d. ≥ × ULN alkaline phosphatase

o ALT or AST >5 × ULN

o Total bilirubin >2 × ULN

o Other LFT abnormalities that would pose an additional risk to the subject in the opinion of investigator or Vertex

Other severe or life-threatening reactions to the study drug in the previous study

5. History of poor compliance with study drug and/or procedures in the previous study as deemed by the investigator.

6. Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor). NOTE: participation in a noninterventional study (including observational studies, registry studies, and studies requiring blood collections without administration of study drug) is permitted.