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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 28 February 2019
Main ID:  EUCTR2016-004479-35-IE
Date of registration: 19/02/2018
Prospective Registration: Yes
Primary sponsor: Vertex Pharmaceuticals Incorporated
Public title: A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 through 11 Years With Cystic Fibrosis
Scientific title: A Phase 3, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of Tezacaftor in Combination With Ivacaftor in Subjects Aged 6 Through 11 Years With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation
Date of first enrolment:
Target sample size: 65
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004479-35
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: yes Placebo: yes Other: no Number of treatment arms in the trial: 4  
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 Denmark France Germany Ireland Poland Switzerland
United Kingdom
Contacts
Name: Clinical Trials and Medical Info   
Address:  50 Northern Avenue MA 02210 Boston United States
Telephone: 001 877 634 8789
Email: medicalinfo@vrtx.com
Affiliation:  Vertex Pharmaceuticals Incorporated
Name: Clinical Trials and Medical Info   
Address:  50 Northern Avenue MA 02210 Boston United States
Telephone: 001 877 634 8789
Email: medicalinfo@vrtx.com
Affiliation:  Vertex Pharmaceuticals Incorporated
Key inclusion & exclusion criteria
Inclusion criteria:
1. Subject’s legally appointed and authorized representative will sign and date an informed consent form (ICF) and the subject will sign and date an assent form (if applicable).
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
3. Subjects (male and female) will be between the ages of 6 and 11 years, inclusive, on the date(s) of informed consent (and assent, if applicable).
4. Subjects who weigh =15 kg without shoes at the Screening Visit.
5. Genotypes as presented in Appendix 1 of the Protocol. Genotype is to be confirmed during screening. If the CFTR screening genotype result is not received before enrollment, a previous CFTR genotype lab report may be used to establish eligibility. Subjects who have been enrolled and whose screening genotype does not confirm study eligibility must be discontinued from the study as described in Section 10.7 of the Protocol. Note: Additional mutations may be evaluated and updates to approved mutations will be communicated to investigative sites through a memorandum.
6. A confirmed diagnosis of CF4 as determined by the following criteria:
a. For subjects who are F508del homozygous: 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 the sweat chloride test result obtained at the Screening Visit).
b. For subjects who are F508del heterozygous:
• 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 [this value may be obtained from a record collected prior to use of Kalydeco] OR from the sweat chloride test result obtained at the Screening Visit); OR
• If the sweat chloride value is <60 mmol/L, there must be documented evidence of chronic sinopulmonary disease4 and/or gastrointestinal disease consistent with a diagnosis of CF as judged by the principal investigator, manifest by at least 1 of the following:
o Persistent colonization/infection, defined as =2 positive respiratory cultures within a 6 month period, with 1 or more typical CF pathogens (e.g., Staphylococcus aureus, Haemophilus influenzae, mucoid and nonmucoid Pseudomonas aeruginosa)
o Chronic cough and sputum production
o Persistent chest radiograph abnormalities consistent with CF pulmonary disease (e.g., bronchiectasis, atelectasis, infiltrates, hyperinflation)
o Nasal polyps, chronic sinusitis as manifest by radiographic or computed tomographic abnormalities of the paranasal sinuses
o Evidence of gastrointestinal disease consistent with the diagnosis of CF
o Significant delays in growth and/or weight gain consistent with the diagnosis of CF
9. Subjects with ppFEV1 of =70 percentage points adjusted for age, sex, height, and ethnicity using the Global Lung Function Initiative (GLI) equation5 at the Screening Visit (Section 11.4.2 of the Protocol).
10. Subjects with a screening LCI2.5 result =7.5.
11. Subjects with stable CF disease as deemed by the investigator at the Screening Visit.

Exclusion criteria:
1. History of any comorbidity reviewed at the Screening Visit 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.
For example, history of cirrhosis with portal hypertension and/or history of risk factors for Torsades de Pointes (e.g., familial long QT syndrome, hypokalemia, heart failure, left ventricular hypertrophy, bradycardia, myocardial infarction, cardiomyopathy, history of arrhythmia [ventricular and atrial fibrillation], obesity, acute neurologic events [subarachnoid hemorrhage, intracranial hemorrhage, cerebrovascular accident, intracranial trauma], and autonomic neuropathy).
2. Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject (as deemed by the investigator).
3. Any of the following abnormal laboratory values at the Screening Visit:
• Hemoglobin <10 g/dL
• Abnormal liver function defined as any 2 or more of the following:
o =3 × upper limit of normal (ULN) aspartate aminotransferase (AST)
o =3 × ULN alanine aminotransferase (ALT)
o =3 × ULN gamma-glutamyl transpeptidase (GGT)
o =3 × ULN alkaline phosphatase (ALP)
o =2 × ULN total bilirubin
• Abnormal liver function defined as any increase of =5 × ULN ALT or AST
• Abnormal renal function defined as glomerular filtration rate =45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation)6
4. 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).
5. Colonization with organisms associated with a more rapid decline in pulmonary status (e.g., Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus) at the Screening Visit. The investigator could be guided by the following suggested criteria for a subject to be considered free of colonization:
• The subject should have had at least 2 respiratory tract cultures negative for these organisms within the past 12 months, with no subsequent positive cultures.
• These 2 respiratory tract cultures should have been separated by at least 3 months.
• One of these 2 respiratory tract cultures should have been obtained within the past 6 months.
6. A standard 12-lead ECG demonstrating QTc >450 msec at the Screening Visit. If QTc exceeds 450 msec at the Screening Visit, the ECG should be repeated 2 more times during the Screening Period, and the average of the 3 QTc values should be used to determine the subject's eligibility.
7. History of solid organ or hematological transplantation at the Screening Visit.
8. Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator that does not align with the following requirements:
• A washout period of 30 days or 5 terminal half-lives of the previous investigational study drug, whichever is longer, must elapse before screening.
o The duration of the elapsed time may be longer if required by local regulations.


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

Product Name: VX-661/ivacaftor 50 mg/ 75 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TEZACAFTOR
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: 50-
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Other descriptive name: VX-770
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use

Product Name: VX-661/ivacaftor 100 mg/ 150 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TEZACAFTOR
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-
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Other descriptive name: 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

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)
Primary Outcome(s)
Main Objective: To evaluate the efficacy of tezacaftor in combination with ivacaftor (TEZ/IVA) in subjects with cystic fibrosis (CF) aged 6 through 11 years, homozygous or heterozygous for F508del
Primary end point(s): Absolute change in lung clearance index2.5 (LCI2.5) from baseline through Week 8
Secondary Objective: To evaluate the safety of TEZ/IVA in subjects with CF aged 6 through 11 years, homozygous or heterozygous for F508del
Timepoint(s) of evaluation of this end point: From Baseline through week 8
Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From Baseline through week 8.
Safety and tolerability will be measured thorough the study.

Secondary end point(s): •Absolute change from baseline in sweat chloride at Week 8
• Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score from baseline through Week 8
• Safety and tolerability as measured by adverse events (AEs), clinically significant changes in laboratory values (serum chemistry, hematology, coagulation studies, lipids, vitamin levels, and urinalysis), standard 12-lead ECGs, vital signs, pulse oximetry, serial lung function measurement, and ophthalmologic examinations.
Secondary ID(s)
VX16-661-115
Source(s) of Monetary Support
Vertex Pharmaceuticals Incorporated
Secondary Sponsor(s)
Ethics review
Status:
Approval date:
Contact:
Results
Results available: Yes
Date Posted: 09/07/2019
Date Completed: 21/12/2018
URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-004479-35/results
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