Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years

• ClinicalTrials.gov Identifier: NCT04537793
• Recruitment Status: Completed
• First Posted: September 3, 2020
• Results First Posted: June 28, 2023
• Last Update Posted: June 28, 2023
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Tracking Information

• First Submitted Date: August 28, 2020
• First Posted Date: September 3, 2020
• Results First Submitted Date: June 2, 2023
• Results First Posted Date: June 28, 2023
• Last Update Posted Date: June 28, 2023
• Actual Study Start Date: November 19, 2020
• Actual Primary Completion Date: June 3, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 2, 2023)

• Part A: Observed Pre-dose Concentration (Ctrough) of ELX,TEZ,IVA, and Relevant Metabolites [ Time Frame: From Day 1 through Day 15 ]
• Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 up to Day 43 ]
• Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From Day 1 up to Week 28 ]

Original Primary Outcome Measures (submitted: August 28, 2020)

• Part A: Observed pre-dose concentration (Ctrough) of ELX, TEZ, IVA, and relevant metabolites [ Time Frame: From Day 1 through Day 15 ]
• Part A: Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From Day 1 up to Day 43 ]
• Part B: Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: From Day 1 up to Week 28 ]

Current Secondary Outcome Measures (submitted: June 2, 2023)

• Part B: Observed Pre-dose Plasma Concentration (Ctrough) of ELX,TEZ,IVA and Relevant Metabolites [ Time Frame: From Day 1 through Week 16 ]
• Part B: Absolute Change in Sweat Chloride (SwCl) [ Time Frame: From Baseline through Week 24 ]
  Sweat samples were collected using an approved collection device.
• Part B: Absolute Change in Lung Clearance Index 2.5 (LCI 2.5) [ Time Frame: From Baseline through Week 24 ]
  The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry.

Original Secondary Outcome Measures (submitted: August 28, 2020)

• Part B: Observed pre-dose plasma concentration (Ctrough) of ELX, TEZ, IVA, and relevant metabolites [ Time Frame: From Day 1 through Week 16 ]
• Part B: Absolute change in sweat chloride (SwCl) [ Time Frame: From Baseline through Week 24 ]
• Part B: Absolute change in lung clearance index 2.5 (LCI 2.5) [ Time Frame: From Baseline through Week 24 ]

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

Descriptive Information

• Brief Title: Evaluation of ELX/TEZ/IVA in Cystic Fibrosis (CF) Subjects 2 Through 5 Years
• Official Title: A Phase 3 Study Evaluating the Safety, Tolerability, and Pharmacokinetics of Elexacaftor/Tezacaftor/Ivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 2 Through 5 Years of Age
• Brief Summary: This study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) triple combination therapy in CF subjects 2 through 5 years of age.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cystic Fibrosis

Intervention

• Drug: ELX/TEZ/IVA
  Fixed dose combination granules for oral administration.
  Other Names:

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

  • VX-770
  • ivacaftor

Study Arms

• Experimental: Part A: ELX/TEZ/IVA
  Participants weighing greater than or equal to (>=)14 kilograms (kg) at screening received elexacaftor (ELX) 100 milligrams (mg) once daily (qd)/tezacaftor (TEZ) 50 mg qd/ivacaftor (IVA) 75 mg every 12 hours (q12h) in the treatment period for 15 days.
  Interventions:

  • Drug: ELX/TEZ/IVA
  • Drug: IVA
• Experimental: Part B: ELX/TEZ/IVA
  Participants weighing (>=)14 kg at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg q12h. Participants weighing (>=)10 kg to less than (<)14 kg received ELX 80 mg qd/TEZ 40 mg qd/IVA 60 mg once every morning (qAM) and 59.5 mg once every evening (qPM) in the treatment period for 24 weeks.
  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: June 2, 2023): 83
• Original Estimated Enrollment (submitted: August 28, 2020): 84
• Actual Study Completion Date: June 3, 2022
• Actual Primary Completion Date: June 3, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Homozygous for the F508del mutation or heterozygous for F508del and a minimal function (MF) mutation (F/F or F/MF genotypes)

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: 2 Years to 5 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, United Kingdom, United States

Administrative Information

• NCT Number: NCT04537793
• Other Study ID Numbers: VX20-445-111; 2020-002251-38 ( 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: June 2023