Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy

• ClinicalTrials.gov Identifier: NCT04058366
• Recruitment Status: Completed
• First Posted: August 15, 2019
• Last Update Posted: January 23, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: August 14, 2019
• First Posted Date: August 15, 2019
• Last Update Posted Date: January 23, 2023
• Actual Study Start Date: December 5, 2019
• Actual Primary Completion Date: December 16, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 14, 2019): Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From Baseline up to Week 100 ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 14, 2019)

• Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: From Baseline up to Week 96 ]
• Absolute change in sweat chloride (SwCl) [ Time Frame: From Baseline up to Week 96 ]
• Absolute change in body mass index (BMI) [ Time Frame: From Baseline up to Week 96 ]
• Absolute change in BMI z-score [ Time Frame: From Baseline up to Week 96 ]
• Absolute change in body weight [ Time Frame: From Baseline up to Week 96 ]
• Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: From Baseline up to Week 96 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy
• Official Title: A Phase 3, Open-label Study Evaluating the Long-term Safety and Efficacy of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
• Brief Summary: This study will evaluate the long-term safety, efficacy, and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a gating or residual function mutation (F/G and F/RF genotypes).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: ELX/TEZ/IVA
  Fixed-dose combination (FDC) tablet for oral administration.
  Other Names:

  • VX-445/VX-661/VX-770
  • elexacaftor/tezacaftor/ivacaftor
• Drug: IVA
  150-mg tablet for oral administration.
  Other Names:

  • VX-770
  • ivacaftor

Study Arms

Experimental: Triple Combination Arm

Subjects will receive ELX/TEZ/IVA TC in the morning and IVA as mono tablet in the evening.

Interventions:

• Drug: ELX/TEZ/IVA
• Drug: IVA

• Publications *: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 10, 2020): 251
• Original Estimated Enrollment (submitted: August 14, 2019): 250
• Actual Study Completion Date: December 16, 2022
• Actual Primary Completion Date: December 16, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Completed study drug treatment in parent study (VX18-445-104); or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study

Key Exclusion Criteria:

• History of study drug intolerance in parent study

Other protocol defined Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Denmark, France, Germany, Ireland, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04058366
• Other Study ID Numbers: VX18-445-110; 2019-000833-37 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: 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.

• Current Responsible Party: Vertex Pharmaceuticals Incorporated
• Original Responsible Party: Same as current
• Current Study Sponsor: Vertex Pharmaceuticals Incorporated
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vertex Pharmaceuticals Incorporated
• Verification Date: January 2023