A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis

• ClinicalTrials.gov Identifier: NCT03912233
• Recruitment Status: Completed
• First Posted: April 11, 2019
• Results First Posted: April 20, 2023
• Last Update Posted: April 20, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: April 10, 2019
• First Posted Date: April 11, 2019
• Results First Submitted Date: October 13, 2021
• Results First Posted Date: April 20, 2023
• Last Update Posted Date: April 20, 2023
• Actual Study Start Date: April 30, 2019
• Actual Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 29, 2023)

• Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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) [ Time Frame: From Baseline Through Day 29 ]
  FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Original Primary Outcome Measures (submitted: April 10, 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 Day 75 ]
• Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1) [ Time Frame: From baseline through Day 29 ]

Current Secondary Outcome Measures (submitted: March 29, 2023)

• Absolute Change in Sweat Chloride (SwCl) Concentrations [ Time Frame: From Baseline Through Day 29 ]
  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 Day 29 ]
  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.
• 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) [ Time Frame: Pre-dose at Day 15 and Day 29 ]

Original Secondary Outcome Measures (submitted: April 10, 2019)

• Absolute change in sweat chloride concentrations [ Time Frame: From baseline through Day 29 ]
• Absolute change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score [ Time Frame: From baseline at Day 29 ]
• Maximum observed concentration (Cmax) of VX-121, TEZ, VX-561, IVA (Part 2), and relevant metabolites [ Time Frame: From Day 1 up to Day 29 ]
• Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-121, TEZ, VX-561, IVA (Part 2), and relevant metabolites [ Time Frame: From Day 1 up to Day 29 ]
• Observed pre-dose concentration (Ctrough) of VX-121, TEZ, VX-561, IVA (Part 2), and relevant metabolites [ Time Frame: From Day 1 up to Day 29 ]

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

Descriptive Information

• Brief Title: A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
• Official Title: 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
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: VX-121
  Tablets for oral administration.
• Drug: TEZ
  TEZ tablet for oral administration.
  Other Names:

  • VX-661
  • Tezacaftor
• Drug: VX-561
  Tablets for oral administration.
  Other Names:

  • CTP-656
  • Deutivacaftor (D-IVA)
• Drug: TEZ/IVA
  Fixed-dose combination tablets for oral administration.
  Other Names:

  • VX-661/VX-770
  • Tezacaftor/Ivacaftor
• Drug: IVA
  Tablets for oral administration.
  Other Names:

  • VX-770
  • Ivacaftor
• Drug: Placebo
  Placebos matched to VX-121, TEZ, and VX-561 for oral administration.

Study Arms

• Placebo Comparator: Part 1: Placebo
  Participants 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.
  Intervention: Drug: Placebo
• Experimental: Part 1: VX-121/TEZ/VX-561 TC - Low Dose
  Participants 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
  Interventions:

  • Drug: VX-121
  • Drug: TEZ
  • Drug: VX-561
• Experimental: Part 1: VX-121/TEZ/VX-561 TC - Medium Dose
  Participants 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.
  Interventions:

  • Drug: VX-121
  • Drug: TEZ
  • Drug: VX-561
• Experimental: Part 1: VX-121/TEZ/VX-561 TC - High Dose
  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/VX-561 150 mg qd for 18 days in the washout period.
  Interventions:

  • Drug: VX-121
  • Drug: TEZ
  • Drug: VX-561
• Active Comparator: Part 2: TEZ/IVA
  Following 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.
  Interventions:

  • Drug: TEZ/IVA
  • Drug: IVA
• Experimental: Part 2: VX-121/TEZ/VX-561 TC - High Dose
  Following 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:

  • Drug: VX-121
  • Drug: TEZ
  • Drug: VX-561

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2019): 87
• Original Estimated Enrollment (submitted: April 10, 2019): 81
• Actual Study Completion Date: December 10, 2019
• Actual Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• 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

Key Exclusion Criteria:

• 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

Other protocol-defined Inclusion/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany, Netherlands, Portugal, United Kingdom, United States

Administrative Information

• NCT Number: NCT03912233
• Other Study ID Numbers: VX18-121-101
• 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
• Product Manufactured in and Exported from the U.S.: Yes

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: March 2023