A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
1 other identifier
interventional
87
5 countries
26
Brief Summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Apr 2019
Shorter than P25 for phase_2
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 10, 2019
CompletedFirst Posted
Study publicly available on registry
April 11, 2019
CompletedStudy Start
First participant enrolled
April 30, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 10, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
December 10, 2019
CompletedResults Posted
Study results publicly available
April 20, 2023
CompletedApril 20, 2023
March 1, 2023
7 months
April 10, 2019
October 13, 2021
March 29, 2023
Conditions
Outcome Measures
Primary Outcomes (2)
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
From Baseline Through Day 29
Secondary Outcomes (3)
Absolute Change in Sweat Chloride (SwCl) Concentrations
From Baseline Through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
From Baseline at Day 29
Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)
Pre-dose at Day 15 and Day 29
Study Arms (6)
Part 1: Placebo
PLACEBO COMPARATORParticipants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period.
Part 1: VX-121/TEZ/VX-561 TC - Low Dose
EXPERIMENTALParticipants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period
Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
EXPERIMENTALParticipants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Part 1: VX-121/TEZ/VX-561 TC - High Dose
EXPERIMENTALParticipants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period.
Part 2: TEZ/IVA
ACTIVE COMPARATORFollowing run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period.
Part 2: VX-121/TEZ/VX-561 TC - High Dose
EXPERIMENTALFollowing run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period.
Interventions
Tablets for oral administration.
TEZ tablet for oral administration.
Tablets for oral administration.
Fixed-dose combination tablets for oral administration.
Eligibility Criteria
You may qualify if:
- Part 1: Heterozygous for F508del and an MF mutation (F/MF)
- Part 2: Homozygous for F508del (F/F)
- FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height
You may not qualify if:
- History of clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- History of solid organ or hematological transplantation
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
Keck Medical Center of University of Southern California
Los Angeles, California, 90033, United States
Kaiser Permanente
Oakland, California, 94611, United States
University of Kentucky.
Lexington, Kentucky, 40536, United States
Tulane Medical Center
New Orleans, Louisiana, 70112, United States
Boston Children's Hospital
Boston, Massachusetts, 02115, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Columbia University Medical Center
New York, New York, 10032, United States
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, 73112, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900, United States
Charite Paediatric Pulmonology Department
Berlin, Germany
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen, Germany
Pneumologisches Studienzentrum Muenchen-West
München, Germany
Academic Medical Center
Amsterdam, Netherlands
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan, Netherlands
UMC St. Radboud
Nijmegen, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
HagaZiekenhuis van den Haag
The Hague, Netherlands
Hospital de Santa Maria
Lisbon, Portugal
University Hospitals Birmingham NHS Foundation Trust
Birmingham, United Kingdom
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London, United Kingdom
Wythenshawe Hospital
Manchester, United Kingdom
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
Penarth, United Kingdom
Related Publications (1)
Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Rubenstein RC, Taylor-Cousar JL, Tullis E, Yonker LM, Chu C, Lam AP, Nair N, Sosnay PR, Tian S, Van Goor F, Viswanathan L, Waltz D, Wang LT, Xi Y, Billings J, Horsley A; VX18-121-101; VX18-561-101 Study Groups. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550-562. doi: 10.1016/S2213-2600(22)00504-5. Epub 2023 Feb 23.
PMID: 36842446DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Monitor
- Organization
- Vertex Pharmaceuticals Incorporated
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 10, 2019
First Posted
April 11, 2019
Study Start
April 30, 2019
Primary Completion
December 10, 2019
Study Completion
December 10, 2019
Last Updated
April 20, 2023
Results First Posted
April 20, 2023
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will not share
Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing