A study in people with cystic fibrosis (a rare hereditary lung disease) to assess the efficacy and safety of two experimental drugs: ivacaftor and VX-661 in combination with ivacaftor

• Register: EUCTR
• Last refreshed on: 19 February 2018
• Main ID: EUCTR2014-004788-18-IT
• Date of registration: 19/03/2015
• 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 two experimental drugs: ivacaftor and VX-661 in combination with ivacaftor
• Scientific title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy and Safety of Ivacaftor and VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Heterozygous for the F508del-CFTR Mutation, and a Second Allele With a CFTR Mutation Predicted to Have Residual Function
• Date of first enrolment: 15/07/2015
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-004788-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: yes; Other: no; Number of treatment arms in the trial: 6
• 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, France, Germany, Israel, Italy, Netherlands, 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 (males and females) will be aged 12 years or older on the date of informed consent or, where appropriate, assent.
• Heterozygous for F508del-CFTR and a second allele with a CFTR mutation predicted to have residual function ; genotype confirmed at the Screening Visit.
• Forced Expiratory Volume in 1 Second (FEV1) greater than or equal to (=) 40 percent (%) and less than or equal to (=) 90% of predicted normal for age, sex, and height during screening.
• Sweat chloride value = 60 mmol/L from test results obtained during screening OR as documented in the subject’s medical record.
• Sweat chloride value <60 mmol/L must have documented evidence of chronic sinopulmonary disease.
• Stable CF disease as judged by the investigator
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
• A 12-lead electrocardiogram (ECG) demonstrating corrected QT interval (QTc) greater than (>) 450 milliseconds (msec) at the Screening Visit
• History of solid organ or hematological transplantation
• History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination during the Screening Period
• Ongoing or prior participation in an investigational drug study (including studies investigating VX-661, lumacaftor [VX-809], and/or ivacaftor) within 30 days of screening
• Use of restricted medications or foods within the specified window before the first dose of study drug
• Pregnant and nursing females (females of childbearing potential must have a negative pregnancy test at Screening and Day 1).
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
• Colonization with organisms associated with a more rapid decline in pulmonary status



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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 17.1 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/150 mg
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: 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: Tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from study baseline to the average of the Week 4 and Week 8 measurements in each Treatment Period.

Main Objective: To evaluate the efficacy of VX-661 in combination with ivacaftor and ivacaftor monotherapy through 8 weeks of treatment in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene and a second allele with a CFTR mutation predicted to have residual function.

Secondary Objective: •To evaluate the safety of VX-661 in combination with ivacaftor through 8 weeks of treatment
•To evaluate the safety of ivacaftor monotherapy through 8 weeks of treatment
•To investigate the pharmacokinetics (PK) of VX-661 and its metabolite M1 (M1-661), and ivacaftor and its metabolite M1 (M1-ivacaftor)

Timepoint(s) of evaluation of this end point: Baseline, Week 4 and week 8 of each treatment period

Secondary Outcome(s)

Secondary end point(s): • Relative change in percent predicted FEV1 from study baseline to the average of the Week 4 and Week 8 measurements in each Treatment Period
• Absolute change in sweat chloride from study baseline to the average of the Week 4 and Week 8 measurements in each Treatment Period
• Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry
• Absolute Change From study Baseline to Average of Week 4 and Week 8 Measurements in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
• PK parameters of VX-661, M1-661, ivacaftor, and M1-ivacaftor

Timepoint(s) of evaluation of this end point: • Relative change in percent predicted FEV1 from study baseline: Baseline, Week 4 and Week 8 of each treatment period
• Absolute change in sweat chloride from study baseline: Baseline, Week 4 and Week 8 of each treatment period
•Safety and tolerability assessments based on adverse events (AEs), clinical laboratory values, standard digital electrocardiograms (ECGs), vital signs, and pulse oximetry: Baseline up to 28 days after last dose (up to 28 weeks)
•Absolute Change From study Baseline in CFQ-RRespiratory Domain Score: Baseline, Week 4 and Week 8 of each treatment period
• PK parameters of VX-661, M1-661, ivacaftor, and M1-ivacaftor: day 1 through week 24

Secondary ID(s)

VX14-661-108

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated