Evaluation of Efficacy and Safety of ELX/TEZ/IVA in Subjects Without an F508del Mutation

• Register: EUCTR
• Last refreshed on: 24 January 2022
• Main ID: EUCTR2021-005320-38-ES
• Date of registration: 01/12/2021
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: Evaluation of Efficacy and Safety of ELX/TEZ/IVA in Subjects Without an F508del Mutation
• Scientific title: A Phase 3 Double-blind, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of ELX/TEZ/IVA in Cystic Fibrosis Subjects 6 Years of Age and Older With a Non-F508del ELX/TEZ/IVA-responsive CFTR Mutation
• Date of first enrolment: 21/01/2022
• Target sample size: 270
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-005320-38
• 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: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; 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

Austria, Belgium, France, Germany, Italy, Netherlands, Portugal, Spain, Switzerland

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 (or the subject's legally appointed and authorized representative) will sign and date an informed consent form (ICF) and, when appropriate, an assent form.
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines (as applicable), and other study procedures.
. For subjects <18 years of age: as judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions and the parent or legal guardian should be able to ensure that the subject will comply with and is likely to complete the study as planned.
3. Subjects (male or female) 6 years of age and older on the date of informed consent.
4. Subjects has an eligible ELX/TEZ/IVA-responsive CFTR mutation listed in Table 15-1 and none of the exclusionary mutations in Table 15-2.
5. Subject has stable CF disease, as deemed by the investigator, before randomization.
6. Forced expiratory volume in 1 second (FEV1) value .40% and .90% of predicted mean for age, sex, and height (equations of the Global Lung Function Initiative [GLI]) at the Screening Visit (spirometry measurements must meet American Thoracic Society/European Respiratory Society criteria for acceptability and repeatability).
7. Subject is able to swallow tablets.
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 120
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. History of any illness or any clinical condition that might confound the results of the study or pose an additional risk in administering study drug(s) to the subject. This may include, but is not limited to:
• Clinically significant liver cirrhosis with or without portal hypertension
• Solid organ or hematological transplantation
• Alcohol or drug abuse in the past year, including, but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator
Cancer, except for squamous cell skin cancer, basal cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no recurrence for the last 5 years).

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 screening:
. Hemoglobin <10 g/dL
. Total bilirubin .2 ~ upper limit of normal (ULN)
. AST, ALT, gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) = 3 x ULN
. Abnormal renal function defined as glomerular filtration rate .50 mL/min/1.73 m2 (calculated by the Modification of Diet in Renal Disease Study Equation)for subjects .18 years of age and .45 mL/min/1.73 m2 (calculated by the Counahan-Barratt equation) for subjects <18 years of age.

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

5. Lung infection with organisms associated with a more rapid decline in pulmonary status (including, but not limited to, Burkholderia cenocepacia, Burkholderia dolosa, and Mycobaterium abscessus). For subjects who have had a history of a positive culture, the investigator will apply the following criteria to establish whether the subject is free of infection with such organisms.
. The subject has not had a respiratory tract culture positive for these organisms within the 12 months before the date of informed consent, and
. The subject has had at least 2 respiratory tract cultures negative for such organisms within the 12 months before the date of informed consent, with the first and last of these separated by at least 3 months, and the most recent one within the 6 months before the date of informed consent.

6. An acute illness not related to CF (e.g., gastroenteritis) within 14 days before the first dose of study drug (Day 1).

7. Ongoing or prior participation in an investigational drug study within 28 days of the Screening Visit.
. A washout period of 5 terminal half-lives of the previous investigational study drug, or 28 days, whichever is longer, must elapse before the Screening Visit.
. The duration of the elapsed time may be longer if required by local regulations.

8. Pregnant and breast-feeding females. Female subjects of childbearing potential (Section 11.5.6.1) must have a negative pregnancy test at the Screening Visit and the Day 1 Visit.

9. Use of restricted medication within specified duration before the first dose of study drug as defined in Table 9-3.

10. Subject, or close relative of the subject, is the investigator or a subinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site. However, an adult (aged 18 years or older) who is a relative of a study staff member may be enrolled in the study provided that:
• the adult l

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: 100mg ELX/50mg TEZ /75mg IVA
Product Code: VX-445/TEZ/IVA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Elexacaftor
CAS Number: 2216712-66-0
Current Sponsor code: VX-445
Other descriptive name: ELX
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Tezacaftor
CAS Number: 1152311-62-0
Current Sponsor code: VX-661
Other descriptive name: TEZ
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Other descriptive name: IVA
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: 150mg IVACAFTOR
Product Code: VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Other descriptive name: IVA
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

Product Name: 75-mg IVACAFTOR
Product Code: VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-770
Other descriptive name: IVA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 75-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: 50 mg ELX/25 mg TEZ/37.5 mg IVA
Product Code: VX-445/TEZ/IVA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ivacaftor
CAS Number: 873054-44-5
Current Sponsor code: VX-

Primary Outcome(s)

Main Objective: To evaluate the efficacy and pharmacodynamics (PD) of ELX/TEZ/IVA

Primary end point(s): Absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) through Week 24

Secondary Objective: To evaluate safety and tolerability of ELX/TEZ/IVA

Timepoint(s) of evaluation of this end point: From signing of ICF until safety Follow up visit.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: From signing of ICF until safety Follow up visit.

Secondary end point(s): •Absolute change from baseline in SwCl through Week 24
• Absolute change from baseline in Cystic Fibrosis Questionnaire- Revised respiratory domain (CFQ-R RD) score through Week 24
• Absolute change from baseline in body mass index (BMI) at Week 24
• Absolute change from baseline in weight at Week 24
• Number of pulmonary exacerbations (PEx) through Week 24
• Safety and tolerability assessments based on AE, clinical laboratory values, ECGs, vital signs, and pulse oximetry

Secondary ID(s)

VX21-445-124

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date: 14/01/2022
Contact: