A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)

• ClinicalTrials.gov Identifier: NCT03460990
• Recruitment Status: Completed
• First Posted: March 9, 2018
• Results First Posted: October 17, 2019
• Last Update Posted: October 17, 2019
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: March 1, 2018
• First Posted Date: March 9, 2018
• Results First Submitted Date: September 26, 2019
• Results First Posted Date: October 17, 2019
• Last Update Posted Date: October 17, 2019
• Actual Study Start Date: May 1, 2018
• Actual Primary Completion Date: September 26, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 26, 2019)

Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) [ Time Frame: From Baseline at Week 4 ]

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

• Original Primary Outcome Measures (submitted: March 7, 2018): Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: from baseline at Week 4 ]

Current Secondary Outcome Measures (submitted: September 26, 2019)

• Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline at Week 4 ]
  Sweat samples were collected using an approved collection device.
• Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score [ Time Frame: From Baseline at Week 4 ]
  The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
• Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8) ]
• Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA [ Time Frame: From Day 1 and Week 4 ]

Original Secondary Outcome Measures (submitted: March 7, 2018)

• Absolute change in CF Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: from baseline at Week 4 ]
• Absolute change in Sweat Chloride (SwCl) [ Time Frame: from baseline at Week 4 ]
• Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: from baseline through 4-week safety follow-up (up to12 weeks) ]
• Observed pre-dose concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA [ Time Frame: from Day 1 through Week 4 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
• Official Title: A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous for the F508del Mutation (F/F)
• Brief Summary: This study will evaluate the efficacy of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F).
• 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: VX-659/TEZ/IVA
  Participants received VX-659/TEZ/IVA orally once daily in the morning.
  Other Names:

  • VX-659/VX-661/VX-770
  • VX-659/tezacaftor/ivacaftor
• Drug: TEZ/IVA
  Participants received TEZ/IVA orally once daily in the morning.
  Other Names:

  • VX-661/VX-770
  • tezacaftor/ivacaftor
• Drug: IVA
  Participants received IVA orally once daily in the evening.
  Other Names:

  • VX-770
  • ivacaftor
• Drug: Placebo
  Participants received placebo matched TEZ/IVA orally once daily in the morning.
• Drug: Placebo
  Participants received placebo matched to VX-659/TEZ/IVA orally once daily in the morning.

Study Arms

• Active Comparator: TEZ/IVA
  Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
  Interventions:

  • Drug: TEZ/IVA
  • Drug: IVA
  • Drug: Placebo
• Experimental: VX-659/TEZ/IVA TC
  Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
  Interventions:

  • Drug: VX-659/TEZ/IVA
  • Drug: IVA
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 3, 2018): 116
• Original Estimated Enrollment (submitted: March 7, 2018): 100
• Actual Study Completion Date: October 8, 2018
• Actual Primary Completion Date: September 26, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Homozygous for the F508del mutation (F/F)
• 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, Germany, Ireland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03460990
• Other Study ID Numbers: VX17-659-103; 2017-004133-82 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

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: Not Provided
• 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: September 2019