A study lasting 96 weeks to assess a combined treatment called Tezacaftor and Ivacaftor in children aged 6 to 11 years who have Cystic Fibrosis

• Register: EUCTR
• Last refreshed on: 12 December 2023
• Main ID: EUCTR2017-002968-40-IE
• Date of registration: 08/03/2018
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A study lasting 96 weeks to assess a combined treatment called Tezacaftor and Ivacaftor in children aged 6 to 11 years who have Cystic Fibrosis
• Scientific title: A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation
• Date of first enrolment: 27/04/2018
• Target sample size: 121
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002968-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: no Placebo: no 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, Belgium, Canada, Denmark, France, Germany, Ireland, Poland, 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:
1. Subject’s legally appointed and authorized representative will sign and date an informed consent form (ICF) and the subject will sign 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. Completed the Week 24 Visit in Study 113B or the Week 8 Visit in Study 115.
4. Did not withdraw consent from the parent study.
5. Subjects must have a genotype listed in Appendix 1: CFTR Mutations.
6. Willing to remain on a stable CF medication regimen through the Safety Follow up Visit
Part B
1. Subject’s legally appointed and authorized representative will sign and date an informed consent form (ICF) and the subject will sign 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. Completed the Week 96 Visit in Part A
4. Did not withdraw consent from Part A.
5. Willing to remain on a stable CF medication regimen through the Safety Follow up Visit.

Are the trial subjects under 18? yes
Number of subjects for this age range: 121
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Part A
1. 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.
For example, history of cirrhosis with portal hypertension, and/or history of risk factors for Torsade 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, and intracranial trauma], and autonomic neuropathy).
2. Pregnant and nursing females. Females who have achieved menarche must have a negative pregnancy test at the Day 1 Visit before receiving the first dose of study drug (Section 11.4.2).
3. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements outlined in Section 11.4.8.
4. History of drug intolerance in the parent study that would pose an additional risk to the subject in the opinion of the investigator, and which should be discussed with the Vertex medical monitor. Examples of subjects who may not be eligible for the study include (but are not limited to) the following:
• Subjects with a history of allergy or hypersensitivity to the study drug
• (LFT) abnormality during study drug treatment in the parent study or other qualified Vertex study that required permanent study drug discontinuation
• Other severe or life-threatening reactions to the study drug in the previous study
5. History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator.
6. Ongoing participation in another study with investigational drug. Ongoing participation in a non-interventional study (including observational studies) is permitted. During the Part A Treatment Period, subjects may screen for another Vertex-sponsored study of CFTR modulators, excluding studies of IVA monotherapy and lumacaftor in combination with IVA. If a subject chooses to enroll in the other Vertex-sponsored study, they will be terminated from Study 116 and will not be allowed to re-enroll in Study 116 Part A.
Part B
1. 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.
For example, history of cirrhosis with portal hypertension, and/or history of risk factors for Torsade de Pointes (e.g., familial long QT syndrome, hypokalemia, heart failure, left ventricular hypertrophy, bradycardia, cardiomyopathy, history of arrhythmia [ventricular and atrial fibrillation], obesity, acute neurologic events [subarachnoid hemorrhage, intracranial hemorrhage, and intracranial trauma], and autonomic neuropathy).
2. Pregnant and nursing females. All female subjects must have a negative pregnancy test at the Day 1 Visit of Part B before receiving the first dose of study drug (Section 11.4.2).
3. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements outlined in Section 11.4.8.
4. History of drug intolerance in the parent study or Part A that would pose an additional risk to the subject in the opinion of the investigator, and which should be discussed with the Vertex medical monitor. Examples of subjects who may not be eligible for the study include (but are not

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

Health Condition(s) or Problem(s) studied

Cystic Fibrosis
MedDRA version: 20.0 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 50 mg/ 75 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TEZACAFTOR
CAS Number: 1152311-62-0
Current Sponsor code: VX661
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-

Trade Name: Symkevi
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/g milligram(s)/gram
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-

Product Name: Ivacaftor
Product Code: VX-770, VRT-813077
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-

Trade Name: Kalydeco 150mg
Product Name: Ivacaftor
Product Code: VX-770, VRT-813077
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IVACAFTOR
CAS Number: 873054-44-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From Baseline through week 96

Main Objective: To evaluate the long-term safety and tolerability of TEZ/IVA in subjects with CF aged 6 years and older, who are homozygous or heterozygous for F508del in Part A

Secondary Objective: To evaluate the long-term efficacy of TEZ/IVA in subjects with CF aged 6 years and older, who are homozygous or heterozygous for F508del in Part A

To evaluate the long-term safety and tolerability of TEZ/IVA in subjects with CF aged 6 years and older, homozygous or heterozygous for the F508del mutation in Part B.

Primary end point(s): Part A: Safety and tolerability of long-term TEZ/IVA treatment based on adverse events (AEs), clinical laboratory values (serum chemistry, hematology, lipids, and vitamins), standard 12-lead ECGs, physical examinations (PEs), vital signs, ophthalmologic examinations, and pulse oximetry.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From Baseline through week 96

Secondary end point(s): Part A
- Absolute change from baseline in lung clearance index2.5 (LCI2.5; for subjects from Study 115 and the Study 113 Part B LCI Substudy only)
- Absolute change from baseline in sweat chloride
- Absolute change from baseline in Cystic Fibrosis Questionnaire–Revised (CFQ-R) respiratory domain score
- Absolute change from baseline in body mass index (BMI)
Part B
Safety and tolerability of long-term TEZ/IVA treatment based on AEs, serum liver function tests (LFTs), and ophthalmologic examinations.

Secondary ID(s)

2017-002968-40-GB

VX17-661-116

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date: 06/04/2018
Contact: