A Phase 3 Study of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation (F/MF)

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2021-000712-31-SE
• Date of registration: 22/09/2021
• Prospective Registration: Yes
• Primary sponsor: Vertex Pharmaceuticals Incorporated
• Public title: A Phase 3 Study of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for F508del and a Minimal Function Mutation (F/MF)
• Scientific title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)
• Date of first enrolment: 18/01/2022
• Target sample size: 400
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2021-000712-31
• 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: yes 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, Czech Republic, Czechia, Germany, Hungary, Ireland, Israel, New Zealand, Portugal, Spain, 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:
1. Subject will sign and date an informed consent form, and when appropriate, an assent form.
2. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
3. Subjects aged 12 years or older, on the date of informed consent
4. Confirmed diagnosis of CF as determined by the investigator
5. Heterozygous for F508del and an MF mutation, defined as a mutation that either results in no translated CFTR protein or that is non-responsive to TEZ, IVA, or TEZ/IVA based on in vitro testing.
6. For subjects currently receiving ELX/TEZ/IVA, FEV1 value =40% and =90% of predicted mean for age, sex, and height at the Screening Visit. All subjects not currently receiving ELX/TEZ/IVA must have an FEV1 value =40% and =80% of predicted mean.
7. Stable CF disease as judged by the investigator.
8. Willing to remain on a stable CF treatment regimen through completion of study participation.

Are the trial subjects under 18? yes
Number of subjects for this age range: 72
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 328
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
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(s) to the subject.
2. History of intolerance to study drug that would pose an additional risk to the subject in the opinion of the investigator.
3. Any of the following abnormal laboratory values at screening:
• Hemoglobin <10 g/dL
• Total bilirubin =2 × upper limit of normal
• Aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, or alkaline phosphatase =3 × ULN
• Abnormal renal function defined as glomerular filtration rate =50 mL/min/1.73 m2 for subjects =18 years of age and =45 mL/min/1.73 m2 for subjects aged 12 to 17 years.
4. An acute upper or lower respiratory infection, PEx, or changes in therapy for sinopulmonary disease within 28 days before the first dose of ELX/TEZ/IVA in the Run-in Period.
5. Lung infection with organisms associated with a more rapid decline in pulmonary status. 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.
• 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 within 14 days before the first dose of ELX/TEZ/IVA in the Run-in Period.
7. Ongoing or prior participation in a study of an investigational treatment other than a Vertex CFTR modulator within 28 days or 5 terminal half-lives before screening, or participation in an interventional study of a non-investigational treatment from screening through end of study participation. The duration of the elapsed time may be longer if required by local regulations.
8. Use of prohibited medications as defined in Table 9 2, within the specified window before the first dose of ELX/TEZ/IVA in the Run-in Period.
9. Pregnant or breast-feeding females. Female subjects must have a negative pregnancy test at screening and Run-in Period/Day -28.
10. The subject or a 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 who is a relative of a study staff member may be enrolled in the study provided that
• the adult lives independently of and does not reside with the study staff member, and
• the adult participates in the study at a site other than the site at which the family member is employed.




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-121/tezacaftor/deutivacaftor
Product Code: VX-121/TEZ/D-IVA
Pharmaceutical Form: Film-coated tablet
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: deutivacaftor
CAS Number: 1413431-07-8
Current Sponsor code: VX-561
Other descriptive name: D-IVA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-
INN or Proposed INN: Not yet assigned
CAS Number: 2374124-50-0
Current Sponsor code: VX-121
Other descriptive name: VX-121
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: elexacaftor/tezacaftor/ivacaftor
Product Code: ELX/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: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: ivacaftor
Product Code: VX-770
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ivacaftor
CAS Number: 8

Primary Outcome(s)

Secondary Objective: To evaluate the safety of VX-121/TEZ/D-IVA
To evaluate the pharmacokinetics (PK) of VX-121/TEZ/D-IVA

Main Objective: To evaluate the efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in cystic fibrosis (CF) subjects who are heterozygous for F508del and a minimal function mutation (F/MF subjects)

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

Timepoint(s) of evaluation of this end point: Baseline through 24 weeks

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Baseline through 24 weeks

Secondary end point(s): • Absolute change from baseline in sweat chloride (SwCl) through Week 24
• Proportion of subjects with SwCl <60 mmol/L through Week 24 (pooled with data from Study VX20-121-103)
• Proportion of subjects with SwCl <30 mmol/L through Week 24 (pooled with data from Study VX20-121-103)

Secondary ID(s)

VX20-121-102

Source(s) of Monetary Support

Vertex Pharmaceuticals Incorporated

Ethics review

Status: Approved
Approval date: 18/01/2022
Contact: