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

• Register: EUCTR
• Last refreshed on: 24 July 2017
• Main ID: EUCTR2012-003989-40-SE
• Date of registration: 18/03/2013
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A study in people with Cystic Fibrosis ( a rare hereditary pulmonary 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 Lumacaftor in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation
• Date of first enrolment: 07/05/2013
• Target sample size: 501
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003989-40
• 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: 3
• 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, Canada, Czech Republic, France, Germany, Ireland, Italy, Netherlands, 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:
• Males and females, aged 12 years or older on the date of informed consent or, where appropriate, date of assent
• Confirmed diagnosis of CF
• Homozygous for the F508del CFTR mutation
• FEV1 =40% and =90% of predicted normal for age, sex, and height
• Willing to remain on a stable CF medication regimen through Week 24 or, if applicable, the Safety Follow up Visit

Are the trial subjects under 18? yes
Number of subjects for this age range: 264
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 349
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before first dose of study drug
• History of solid organ or hematological transplantation
• History of alcohol or drug abuse in the past year
• Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening
• Use of strong inhibitors, moderate inducers, or strong inducers of
CYP3A, including consumption of certain herbal medications (e.g., St.
John's Wort) and certain fruit and fruit juices within 14 days before Day
1


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

Health Condition(s) or Problem(s) studied

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

Cystic fibrosis in patients homozygous for the F508del-CFTR Mutation
MedDRA version: 16.1 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders

Intervention(s)

Product Name: lumacaftor/ivacaftor 200mg/125mg tablets
Product Code: VX-809 / VX-770
Pharmaceutical Form: Film-coated tablet
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-
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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: lumacaftor/ivacaftor 200mg/83mg tablet
Pharmaceutical Form: Film-coated tablet
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-
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: 83-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: ivacaftor 125mg tablet
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-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of lumacaftor in combination with ivacaftor at
Week 24 in subjects with cystic fibrosis (CF) who are homozygous for
the F508del mutation on the CF transmembrane conductance regulator
(CFTR) gene

Primary end point(s): Absolute change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline at Week 24

Secondary Objective: To evaluate the safety of lumacaftor in combination with ivacaftor through Week 24

To investigate the pharmacokinetics (PK) of lumacaftor and its metabolite, M28 (M28 lumacaftor) and ivacaftor and its metabolites M1 and M6 (M1 ivacaftor and M6 ivacaftor)

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Weeks 24 and 28

Secondary end point(s): Relative change in percent predicted forced expiratory volume in 1 second (FEV1) from baseline at Week 24

Absolute change in body mass index (BMI) from baseline at Week 24

Number of pulmonary exacerbations from baseline through Week 24

Absolute change in Cystic Fibrosis Questionnaire – Revised (CFQ-R) respiratory domain score from baseline at Week 24

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

Secondary ID(s)

VX12-809-103

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated