A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

• ClinicalTrials.gov Identifier: NCT04058353
• Recruitment Status: Completed
• First Posted: August 15, 2019
• Last Update Posted: July 13, 2020
• 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: July 13, 2020
• Actual Study Start Date: August 28, 2019
• Actual Primary Completion Date: June 12, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 14, 2019): Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) for ELX/TEZ/IVA group [ Time Frame: From Baseline through Week 8 ]
• Original Primary Outcome Measures: Same as current

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

• Absolute change in sweat chloride (SwCl) for ELX/TEZ/IVA group [ Time Frame: From Baseline through Week 8 ]
• Absolute change in ppFEV1 for ELX/TEZ/IVA group compared to the control group [ Time Frame: From Baseline through Week 8 ]
• Absolute change in SwCl for ELX/TEZ/IVA group compared to the control group [ Time Frame: From Baseline through Week 8 ]
• Absolute change from baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score for ELX/TEZ/IVA group [ Time Frame: From Baseline through Week 8 ]
• Absolute change in CFQ-R respiratory domain score for ELX/TEZ/IVA group compared to the control group [ Time Frame: From Baseline through Week 8 ]
• 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 12 ]

• 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: A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
• Official Title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety 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 efficacy, safety 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 F508del 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: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); 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
• Drug: TEZ/IVA
  FDC tablet for oral administration
  Other Names:

  • VX-661/VX-770
  • tezacaftor/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
• Active Comparator: Control Arm
  Subjects will receive either IVA as mono tablet OR TEZ/IVA as FDC in the morning and IVA as mono tablet in the evening.
  Interventions:

  • Drug: IVA
  • Drug: TEZ/IVA

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 14, 2020): 271
• Original Estimated Enrollment (submitted: August 14, 2019): 250
• Actual Study Completion Date: June 12, 2020
• Actual Primary Completion Date: June 12, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
• Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

Key Exclusion Criteria:

• Clinically significant cirrhosis with or without portal hypertension
• Lung infection with organisms associated with a more rapid decline in pulmonary status
• Solid organ or hematological transplantation

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, Israel, Italy, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04058353
• Other Study ID Numbers: VX18-445-104; 2018-002835-76 ( 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

• Responsible Party: Vertex Pharmaceuticals Incorporated
• Study Sponsor: Vertex Pharmaceuticals Incorporated
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vertex Pharmaceuticals Incorporated
• Verification Date: July 2020