Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment with Lumacaftor in Combination with Ivacaftor.

• Register: EUCTR
• Last refreshed on: 2 June 2020
• Main ID: EUCTR2015-001644-11-GB
• Date of registration: 10/11/2015
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment with Lumacaftor in Combination with Ivacaftor.
• Scientific title: A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 6 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
• Date of first enrolment: 22/01/2016
• Target sample size: 256
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001644-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Denmark, France, Germany, Sweden, United Kingdom, United States

Contacts

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

• Name: Clinical Trials and Medical Info
• Affiliation: Vertex Pharmaceuticals Incorporated

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects who meet all of the following inclusion criteria will be eligible.
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
-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
•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
•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.
•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) 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.

Are the trial subjects under 18? yes
Number of subjects for this age range: 256
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

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:
oAbnormal liver function defined as any 2 or more of the following:
a.=3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
b.=3 × ULN alanine aminotransferase (ALT)
c.=3 × ULN gamma glutamyl transpeptidase
d.=3 × ULN alkaline phosphatase
oALT or AST >5 × ULN
oTotal bilirubin >2 × ULN
oOther 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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Intervention(s)

Product Name: lumacaftor/ivacaftor 100mg/125mg tablets
Product Code: VX-809 / VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: lumacaftor
CAS Number: 936727-05-8
Current Sponsor code: VX 809
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: lumacaftor/ivacaftor 200mg/125mg tablets
Product Code: VX-809 / VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: Lumacaftor
CAS Number: 936727-05-8
Current Sponsor code: VX 809
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): Treatment Cohort:
Safety and tolerability assessments of long term treatment of lumacaftor in combination with ivacaftor based on adverse events (AEs), clinical laboratory values (serum chemistry, hematology, coagulation studies, and urinalysis), standard 12 lead electrocardiograms (ECGs), vital signs, pulse oximetry, ophthalmological examinations, and spirometry
Observational Cohort:
Not applicable

Main Objective: To evaluate the long term safety and tolerability of lumacaftor in combination with ivacaftor in subjects aged 6 years and older with cystic fibrosis (CF), homozygous for the F508del CFTR mutation, who are in the Treatment Cohort

Timepoint(s) of evaluation of this end point: From baseline through week 96 with a Safety Follow up Visit 4 weeks [± 7 days] after the last dose).

Secondary Objective: •To evaluate the long term efficacy and durability of lumacaftor in combination with ivacaftor for subjects in the Treatment Cohort
•To evaluate the post treatment safety of lumacaftor in combination with ivacaftor for subjects in the Observational Cohort

Secondary Outcome(s)

Secondary end point(s): Treatment Cohort:
The following efficacy endpoints will be analyzed using baseline values in the previous study:
•Absolute change from baseline in LCI2.5 (subjects from Study 109 and the Study 011B LCI Substudy only)
•Absolute change from baseline in sweat chloride
•Absolute change from baseline in body mass index (BMI)
•Absolute change from baseline in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score
The following efficacy endpoints will be analyzed using baseline values in the current study:
•Absolute change from baseline in LCI2.5 (subjects from Study 109 and the Study 011B LCI Substudy only)
•Absolute change from baseline in sweat chloride
•Absolute change from baseline in BMI
•Absolute change from baseline in CFQ R respiratory domain score
Observational Cohort:
Safety, as determined by serious adverse events (SAEs)

Timepoint(s) of evaluation of this end point: From baseline through week 96 with a Safety Follow up Visit 4 weeks [± 7 days] after the last dose).

Secondary ID(s)

VX15-809-110

2015-001644-11-SE

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date: 22/01/2016
Contact: