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

• Register: EUCTR
• Last refreshed on: 5 September 2016
• Main ID: EUCTR2014-004787-37-AT
• Date of registration: 18/06/2015
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A study in people with Cystic Fibrosis (a rare hereditary lung disease) to assess the efficacy and safety of a combination of two experimental drugs.
• Scientific title: A Phase 3, Randomized, Double-blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation and With a Second CFTR Mutation That Is Not Likely to Respond to VX-661 and/or Ivacaftor Therapy (F508del/NR)
• Date of first enrolment: 21/09/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004787-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• 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, Austria, Canada, France, Germany, Israel, Spain, 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:
Heterozygous for the F508del-CFTR mutation and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy. If the CFTR screening genotype result is not received before randomization, a previous CFTR genotype laboratory report may be used to establish eligibility.

Confirmed diagnosis of CF defined as a sweat chloride value =60 mmol/L by quantitative pilocarpine iontophoresis (as documented in the subject’s medical record OR from sweat chloride test result obtained at the Screening, if subject does not have a sweat chloride test result in the medical record).


FEV1 =40% and =90% of predicted normal for age, sex, and height at Screening Visit. Spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability.

Stable CF disease as judged by the investigator.

Willing to remain on a stable CF medication regimen through Week 12 or, if applicable, the Safety Follow-up Visit.
Are the trial subjects under 18? yes
Number of subjects for this age range: 150
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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.

An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug).

Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1.




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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 19.0 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 100mg/150mg
Product Code: VX-661/VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not yet assigned
CAS Number: 1152311-62-0
Current Sponsor code: VX-661
Other descriptive name: VRT-893661 VRT-0893661
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Week 12

Primary end point(s): Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline through Week 12.

Secondary Objective: To evaluate the safety of VX-661 in combination with ivacaftor and to investigate the pharmacokinetics (PK) of VX-661 and its metabolite M1-661, and ivacaftor and its metabolite M1-ivacaftor

Main Objective: To evaluate the efficacy of VX-661 in combination with ivacaftor through Week 12 in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and with a second CFTR mutation that is not likely to respond to VX-661 and/or ivacaftor therapy (F508del/not responsive [NR])

Secondary Outcome(s)

Secondary end point(s): Relative change in percent predicted FEV1 from baseline through Week 12

Absolute change in sweat chloride from baseline through Week 12

Absolute change in body mass index (BMI) from baseline at Week 12

Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline through Week 12

Number of pulmonary exacerbations through Week 12

Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values (i.e., hematology, coagulation studies, serum chemistry, vitamin levels, lipid panel, and urinalysis), standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry

Time-to-first pulmonary exacerbation through Week 12

Absolute change in BMI z-score from baseline at Week 12 (in subjects <20 years old at time of screening)

Absolute change in body weight from baseline at Week 12

PK parameters of VX-661, M1-661, ivacaftor, and M1 ivacaftor

Timepoint(s) of evaluation of this end point: Week 12

Secondary ID(s)

VX14-661-107

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated