Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

A Phase 1/2 Study of VX-121 in Healthy Subjects and in Subjects With Cystic Fibrosis

The purpose of this study is to evaluate safety and tolerability of VX-121 in healthy subjects and in subjects with cystic fibrosis (CF).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: IVA; Drug: Placebo (matched to IVA); Drug: Placebo (matched to VX-121 suspension); Drug: VX-121 (Suspension); Drug: VX-121 (Tablet); Drug: Placebo (matched to TEZ/IVA); Drug: TEZ/IVA; Drug: Placebo (matched to VX-121 tablet)

• Study Type: Interventional
• Enrollment (Actual): 115
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Academic Medical Center
  • Den Haag, Netherlands
    • HagaZiekenhuis van Den Haag
  • Groningen, Netherlands
    • PRA Health Sciences Onderzoekscentrum UMCG
  • Nijmegen, Netherlands
    • UMC St. Radboud
  • Rotterdam, Netherlands
    • Erasmus Medical Center
• United Kingdom
  • Birmingham, United Kingdom
    • Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
  • Manchester, United Kingdom
    • The Medicines Evaluation Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Part A, B, and C: Healthy Volunteers

  • Female subjects must be of non-childbearing potential
  • Between the ages of 18 and 55 years, inclusive
  • Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive, and a total body weight >50 kg

• Part D: Subjects with CF

  • Heterozygous for F508del and an MF mutation (F/MF)
  • FEV1 value ≥40% and ≤90% of predicted mean for age, sex, and height
  • Body weight ≥35 kg

Key Exclusion Criteria:

• Part A, B and C: Healthy Volunteers

  • Any condition possibly affecting drug absorption
  • History of febrile illness or other acute illness within 5 days before the first study drug dose

• Part D: Subjects with CF

  • History of clinically significant cirrhosis with or without portal hypertension
  • History of solid organ or hematological transplantation
  • Lung infection with organisms associated with a more rapid decline in pulmonary status

Other protocol defined Inclusion/Exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part A: Pooled Placebo (Cohorts A1-5; Except A3); Participants received single dose of placebo matched to VX-121.	Drug: Placebo (matched to VX-121 suspension); Placebo matched to VX-121 suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A1); Participants received single dose of VX-121 10 milligrams (mg).	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A2); Participants received single dose of VX-121 20 mg.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A3); Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.	Drug: Placebo (matched to VX-121 suspension); Placebo matched to VX-121 suspension for oral administration.; Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A4); Participants received single dose of VX-121 40 mg.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A5); Participants received single dose of VX-121 60 mg.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part A: VX-121 (Cohort A9); Participants received single dose of VX-121 10 mg suspension on Day 1, VX-121 10 mg tablet on Day 9, followed by VX-121 10 mg tablet with milk on Day 17.	Drug: VX-121 (Suspension); Suspension for oral administration.; Drug: VX-121 (Tablet); Tablet for oral administration.
Placebo Comparator: Part B: Pooled Placebo (Cohorts B1-4); Participants received placebo matched to VX-121 for 10 days.	Drug: Placebo (matched to VX-121 suspension); Placebo matched to VX-121 suspension for oral administration.
Experimental: Part B: VX-121 (Cohort B1); Participants received VX-121 10 mg once daily (qd) for 10 days.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part B: VX-121 (Cohort B2); Participants received VX-121 20 mg qd for 10 days.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part B: VX-121 (Cohort B3); Participants received VX-121 40 mg qd for 10 days.	Drug: VX-121 (Suspension); Suspension for oral administration.
Experimental: Part B: VX-121 (Cohort B4); Participants received VX-121 60 mg qd for 10 days.	Drug: VX-121 (Suspension); Suspension for oral administration.
Placebo Comparator: Part C: Pooled Placebo (Cohorts C1-3); Participants received placebo matched to VX-121/TEZ/IVA for 14 days.	Drug: Placebo (matched to IVA); Placebo matched to IVA for oral administration.; Drug: Placebo (matched to VX-121 suspension); Placebo matched to VX-121 suspension for oral administration.; Drug: Placebo (matched to TEZ/IVA); Placebo matched to TEZ/IVA for oral administration.
Experimental: Part C: VX-121 (Cohort C1); Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-121 (Suspension); Suspension for oral administration.; Drug: TEZ/IVA; Fixed-dose combination tablet for oral administration.; Other Names: VX-661/VX-770; tezacaftor/ivacaftor
Experimental: Part C: VX-121 (Cohort C2); Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-121 (Suspension); Suspension for oral administration.; Drug: TEZ/IVA; Fixed-dose combination tablet for oral administration.; Other Names: VX-661/VX-770; tezacaftor/ivacaftor
Experimental: Part C: VX-121 (Cohort C3); Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-121 (Suspension); Suspension for oral administration.; Drug: TEZ/IVA; Fixed-dose combination tablet for oral administration.; Other Names: VX-661/VX-770; tezacaftor/ivacaftor
Placebo Comparator: Part D: Placebo; Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.	Drug: Placebo (matched to IVA); Placebo matched to IVA for oral administration.; Drug: Placebo (matched to TEZ/IVA); Placebo matched to TEZ/IVA for oral administration.; Drug: Placebo (matched to VX-121 tablet); Placebo matched to VX-121 tablet for oral administration.
Experimental: Part D: VX-121/TEZ/IVA; Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.	Drug: IVA; Tablet for oral administration.; Other Names: VX-770; ivacaftor; Drug: VX-121 (Tablet); Tablet for oral administration.; Drug: TEZ/IVA; Fixed-dose combination tablet for oral administration.; Other Names: VX-661/VX-770; tezacaftor/ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	From Day 1 Through Safety Follow-up (up to Day 15 for Part A [except Cohorts A3 and A9], up to Day 26 for Cohort A3, up to Day 34 for Cohort A9, up to Day 20 for Part B, up to Day 24 for Part C and up to Week 9 for Part D)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Maximum Observed Concentration (Cmax) of VX-121		Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Part A: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121		Cohorts A1-5 (Except A3): Pre-dose up to 240 hours post-dose; Cohorts A3 and A9: Pre-dose up to 168 hours post-dose
Part B: Maximum Observed Concentration (Cmax) of VX-121		Day 1, Day 5, and Day 10
Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121		Day 1, Day 5, and Day 10
Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121		Pre-dose at Day 5 and Day 10
Part C: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and, IVA and Its Metabolites (M1-IVA and M6-IVA)		Day 1, Day 7, and Day 14
Part C: Area Under the Concentration Versus Time Curve During a Dosing Interval (AUCtau) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)		Day 1, Day 7, and Day 14
Part C: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)		Pre-dose at Day 7 and Day 14
Part D: Maximum Observed Concentration (Cmax) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)		Day 1 and Day 15
Part D: Area Under the Concentration Versus Time Curve From the Time of Dosing to the Last Measurable Concentration (AUC[0-last]) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)		Day 1 and Day 15
Part D: Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolites (M1-TEZ and M2-TEZ) and IVA and Its Metabolites (M1-IVA and M6-IVA)		Pre-dose at Day 8, Day 15, and Day 29
Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations	Sweat samples were collected using an approved collection device.	From Baseline Through Day 29
Part D: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Baseline Through Day 29

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Actual): May 3, 2019
• Study Completion (Actual): May 3, 2019

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 5, 2018
• First Posted (Actual): December 7, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX17-121-001; 2018-000126-55 (EudraCT Number)

Drug and device information, study documents

• 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