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

Phase 1

Completed

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

• Registration Number: NCT03768089
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2018-03-20
• Study First Submitted: 2018-12-05
• Study First Submitted QC: 2018-12-05
• Study First Posted: 2018-12-07
• Primary Completion: 2019-05-03
• Study Completion: 2019-05-03
• Disposition First Submitted: 2020-05-01
• Results First Submitted: 2022-04-29
• Status Verified: 2022-06
• Results First Submitted QC: 2022-06-17
• Disposition First Submitted QC: 2022-06-17
• Last Update Submitted: 2022-06-17
• Results First Posted: 2022-07-14
• Disposition First Posted: 2022-07-14
• Last Update Posted: 2022-07-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 115

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: VX-121 (Cohort A4)	VX-121 (Suspension)	Participants received single dose of VX-121 40 mg.
Part A: VX-121 (Cohort A1)	VX-121 (Suspension)	Participants received single dose of VX-121 10 milligrams (mg).
Part A: VX-121 (Cohort A3)	VX-121 (Suspension)	Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
Part C: VX-121 (Cohort C2)	VX-121 (Suspension)	Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part A: VX-121 (Cohort A9)	VX-121 (Suspension)	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.
Part A: VX-121 (Cohort A9)	VX-121 (Tablet)	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.
Part B: VX-121 (Cohort B1)	VX-121 (Suspension)	Participants received VX-121 10 mg once daily (qd) for 10 days.
Part C: VX-121 (Cohort C3)	VX-121 (Suspension)	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part D: VX-121/TEZ/IVA	VX-121 (Tablet)	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
Part D: VX-121/TEZ/IVA	TEZ/IVA	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.
Part B: Pooled Placebo (Cohorts B1-4)	Placebo (matched to VX-121 suspension)	Participants received placebo matched to VX-121 for 10 days.
Part B: VX-121 (Cohort B2)	VX-121 (Suspension)	Participants received VX-121 20 mg qd for 10 days.
Part C: Pooled Placebo (Cohorts C1-3)	Placebo (matched to VX-121 suspension)	Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
Part A: VX-121 (Cohort A2)	VX-121 (Suspension)	Participants received single dose of VX-121 20 mg.
Part C: VX-121 (Cohort C1)	TEZ/IVA	Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
Part C: VX-121 (Cohort C2)	IVA	Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part C: VX-121 (Cohort C3)	TEZ/IVA	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part D: Placebo	Placebo (matched to TEZ/IVA)	Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
Part D: Placebo	Placebo (matched to IVA)	Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
Part D: Placebo	Placebo (matched to VX-121 tablet)	Participants received placebo matched to VX-121/TEZ/IVA for 4 weeks.
Part A: VX-121 (Cohort A3)	Placebo (matched to VX-121 suspension)	Participants received single dose of VX-121 5 mg or matched placebo without milk, followed by open label VX-121 5 mg with milk.
Part A: Pooled Placebo (Cohorts A1-5; Except A3)	Placebo (matched to VX-121 suspension)	Participants received single dose of placebo matched to VX-121.
Part A: VX-121 (Cohort A5)	VX-121 (Suspension)	Participants received single dose of VX-121 60 mg.
Part B: VX-121 (Cohort B3)	VX-121 (Suspension)	Participants received VX-121 40 mg qd for 10 days.
Part B: VX-121 (Cohort B4)	VX-121 (Suspension)	Participants received VX-121 60 mg qd for 10 days.
Part C: Pooled Placebo (Cohorts C1-3)	Placebo (matched to TEZ/IVA)	Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
Part C: Pooled Placebo (Cohorts C1-3)	Placebo (matched to IVA)	Participants received placebo matched to VX-121/TEZ/IVA for 14 days.
Part C: VX-121 (Cohort C1)	VX-121 (Suspension)	Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
Part C: VX-121 (Cohort C1)	IVA	Participants received VX-121 10 mg qd/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 14 days.
Part C: VX-121 (Cohort C3)	IVA	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part C: VX-121 (Cohort C2)	TEZ/IVA	Participants received VX-121 20 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 14 days.
Part D: VX-121/TEZ/IVA	IVA	Participants received VX-121 5 mg qd/TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline Through Day 29	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Part B: Maximum Observed Concentration (Cmax) of VX-121	Day 1, Day 5, and Day 10
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 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 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 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: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121	Pre-dose at Day 5 and Day 10
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 B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121	Day 1, Day 5, and Day 10
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 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	From Baseline Through Day 29	Sweat samples were collected using an approved collection device.

Trial Locations

Locations (7)

HagaZiekenhuis van den Haag; 🇳🇱 Den Haag, Netherlands

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands

UMC St. Radboud; 🇳🇱 Nijmegen, Netherlands

PRA Health Sciences Onderzoekscentrum UMCG; 🇳🇱 Groningen, Netherlands

Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

Erasmus Medical Center; 🇳🇱 Rotterdam, Netherlands

The Medicines Evaluation Unit; 🇬🇧 Manchester, United Kingdom