A study to assess the efficacy and safety of a combination of two experimental drugs in people with cystic fibrosis (a rare hereditary lung disease)

• Register: EUCTR
• Last refreshed on: 21 September 2015
• Main ID: EUCTR2014-004827-29-IT
• Date of registration: 08/07/2015
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A study to assess the efficacy and safety of a combination of two experimental drugs in people with cystic fibrosis (a rare hereditary lung disease)
• Scientific title: A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long term Treatment With VX 661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del CFTR Mutation
• Date of first enrolment: 01/09/2015
• Target sample size: 1375
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004827-29
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes 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

Countries of recruitment

Australia, Austria, Belgium, Canada, Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, 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 entering the Treatment Cohort must meet all of the following criteria:
•Elect to enroll in the Treatment Cohort.
•Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109) or study drug treatment and the Safety Follow up Visit for subjects from Study 111.
• Willing to remain on a stable CF medication (and supplement) regimen through the Safety Follow-up Visit.

Subjects entering the Observational Cohort must meet the following criteria:
• <18 years of age (age on the date of informed consent/assent in the parent study)
• Completed study drug treatment during the Treatment Period in a parent study (Studies 103, 106, 107, 108, or 109) or study drug treatment and the Safety Follow up Visit for subjects from Study 111, but do not elect to enroll in the Study 110 Treatment Cohort;
or
• Received at least 4 weeks of study drug treatment in a parent study, but do not meet eligibility criteria for enrollment into the Treatment Cohort.

Are the trial subjects under 18? yes
Number of subjects for this age range: 645
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 730
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Treatment Cohort only:
• History of any comorbidity 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.
• Pregnant and nursing females. Females of childbearing potential must have a negative urine pregnancy test at the Day 1 Visit and before receiving the first dose of study drug.
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
• History of drug intolerance in the parent study that would pose an additional risk to the subject.
• History of poor compliance with study drug and/or procedures in the parent study as deemed by the investigator.
• Participation in an investigational drug trial other than Studies 103, 106, 107, 108, 109, and 111 or use of a commercially available CFTR modulator (e.g., Kalydeco).


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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 18.0 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: VX-661/ivacaftor (VX-770) 100mg/150 mg
Product Code: VX-661/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: 150-
INN or Proposed INN: Not yet assigned
CAS Number: 1152311-62-0
Current Sponsor code: VX-661
Other descriptive name: VRT-893661
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Kalydeco
Product Name: Ivacaftor
Product Code: VX-770, VRT-813077
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: 150-

Primary Outcome(s)

Primary end point(s): For the Treatment Cohort:
Safety and tolerability of long-term treatment of VX-661 in combination with ivacaftor based on adverse events (AEs), ophthalmologic examinations (subjects <18 years of age, clinical laboratory values (serum chemistry, hematology, coagulation, lipids, vitamins, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry

Timepoint(s) of evaluation of this end point: 96 weeks

Main Objective: To evaluate the long-term safety and tolerability of VX-661 in combination with ivacaftor in subjects with CF, homozygous or heterozygous for the F508del-CFTR mutation who are in the Treatment Cohort.

Secondary Objective: To evaluate the long-term efficacy of VX-661 in combination with ivacaftor for subjects in the Treatment Cohort.

To evaluate the post-treatment safety of VX-661 in combination with ivacaftor for subjects in the Observational Cohort.

Secondary Outcome(s)

Secondary end point(s): For the Treatment Cohort:
• Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1)
• Relative change from baseline in ppFEV1
• Number of pulmonary exacerbations
• Absolute change from baseline in body mass index (BMI)
• Absolute change from baseline in BMI z score for subjects aged <20 years
• Absolute change from baseline in Cystic Fibrosis Questionnaire–Revised (CFQ R) respiratory domain score
• Absolute change from baseline in body weight
• Absolute change from baseline in body weight z-score for subjects aged <20 years
• Absolute change from baseline in height z-score for subjects aged <20 years
• Time to first pulmonary exacerbation,
• Pharmacokinetic (PK) parameters of VX 661, a VX-661 metabolite (M1 661), ivacaftor, and an ivacaftor metabolite (M1 ivacaftor)

For the Observational Cohort:
• Safety, as determined by related serious adverse events (SAEs)

Timepoint(s) of evaluation of this end point: Through 100 weeks (Week 24 for PK endpoint)

Secondary ID(s)

VX14-661-110

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated