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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03768089
• Other study ID #: VX17-121-001
• Secondary ID: 2018-000126-55
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 20, 2018
• Est. completion date: May 3, 2019

Study information

• Verified date: June 2022
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 115
• Est. completion date: May 3, 2019
• Est. primary completion date: May 3, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• Placebo (matched to VX-121 suspension)
Placebo matched to VX-121 suspension for oral administration.
• VX-121 (Suspension)
Suspension for oral administration.
• TEZ/IVA
Fixed-dose combination tablet for oral administration.
• IVA
Tablet for oral administration.
• Placebo (matched to TEZ/IVA)
Placebo matched to TEZ/IVA for oral administration.
• Placebo (matched to IVA)
Placebo matched to IVA for oral administration.
• VX-121 (Tablet)
Tablet for oral administration.
• Placebo (matched to VX-121 tablet)
Placebo matched to VX-121 tablet for oral administration.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Part B: Maximum Observed Concentration (Cmax) of VX-121		Day 1, Day 5, and Day 10
Secondary	Part B: Area Under the Concentration Versus Time Curve During the Dosing Interval (AUCtau) of VX-121		Day 1, Day 5, and Day 10
Secondary	Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121		Pre-dose at Day 5 and Day 10
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part D: Absolute Change in Sweat Chloride (SwCl) Concentrations	Sweat samples were collected using an approved collection device.	From Baseline Through Day 29
Secondary	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