Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Sponsor:

Collaborators:

Information provided by (Responsible Party):

，

Tracking Information

First Submitted Date ^ICMJE

September 28, 2018

First Posted Date ^ICMJE

October 2, 2018

Last Update Posted Date

October 2, 2018

Actual Study Start Date ^ICMJE

October 2018

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

Part A: Observed pre-dose concentration (Ctrough) of VX-445, TEZ, and IVA[ Time Frame: Day 1 through 15 ]

Part A: Maximum Observed Concentration (Cmax) of VX-445, TEZ, and IVA[ Time Frame: Day 1 through 15 ]

Part A: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ, and IVA[ Time Frame: Day 1 through 15 ]

Part B: Safety and tolerability as assessed by number of subjects with adverse events and serious adverse events[ Time Frame: from baseline through safety follow-up (28 Weeks) ]

Original Primary Outcome Measures ^ICMJE

Same as current

Current Secondary Outcome Measures ^ICMJE

Part A: Maximum observed concentration (Cmax) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
Part A: Observed pre-dose concentration (Ctrough) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
Part A: Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-445, TEZ, and IVA metabolites[ Time Frame: from Day 1 through 15 ]
Part A: Safety and tolerability as assessed by number of subjects with adverse events (AEs) and serious adverse events (SAEs)[ Time Frame: from baseline through safety follow-up (28 Weeks) ]
Part B: Absolute change in percent predicted forced expiratory volume in 1 second (ppFEV1)[ Time Frame: from baseline through Weeks 12 and 24 ]
Part B: Absolute change in sweat chloride[ Time Frame: from baseline through Weeks 12 and 24 ]
Part B: Absolute change in Cystic Fibrosis Questionnaire Revised (CFQ R) respiratory domain score[ Time Frame: from baseline through Weeks 12 and 24 ]
Part B: Absolute change in body mass index (BMI) and BMI for age-z-score[ Time Frame: from baseline at Week 24 ]
Part B: Absolute change in weight and weight for age-z-score[ Time Frame: from baseline at Week 24 ]
Part B: Absolute change in height and height for age-z-score[ Time Frame: from baseline at Week 24 ]
Part B: Absolute change in the Modified Facial Hedonic Scale[ Time Frame: from baseline at Week 24 ]
Parts B: Ctrough of VX-445, TEZ, IVA, and IVA metabolites[ Time Frame: Day 1 through Week 24 ]
Part B: Absolute change in lung clearance index2.5 (LCI2.5)[ Time Frame: from baseline through Week 24 ]

Descriptive Information

Brief Title ^ICMJE

Evaluation of VX 445/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Official Title ^ICMJE

A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-445/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Brief Summary

This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-445, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects 6 through 11 years of age with F/F and F/MF genotypes.

Detailed Description

Study Type ^ICMJE

Interventional

Study Phase

Phase 3

Study Design ^ICMJE

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:
Masking: Interventional
Masking Description:
Primary Purpose: Treatment

Condition ^ICMJE

Intervention ^ICMJE

Drug: VX-445
Fixed dose combination (FDC) tablet (VX-445/TEZ/IVA)
Drug: TEZ
FDC tablet (VX-445/TEZ/IVA)
Drug: IVA
FDC tablet (VX-445/TEZ/IVA) and IVA mono tablet

Study Arms

Experimental: Part A: Triple Combination
Subjects will receive 100 mg VX-445/ 50 mg TEZ/ 75 mg IVA as an FDC tablet in the morning and 75 mg IVA as mono tablet in the evening.
Experimental: Part B: Triple Combination
Subjects will receive VX-445/TEZ/IVA as FDC tablet in the morning and IVA as mono tablet in the evening with the dose to be based on the outcome of Part A.

Recruitment Information

Recruitment Status ^ICMJE

Not yet recruiting

Estimated Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Same as current

Estimated Study Completion Date

January 2020

Estimated Primary Completion Date

January 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

Key Inclusion Criteria: - Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes) - Forced expiratory volume in 1 second (FEV1) value ≥40% of predicted mean for age, sex, and height. Key Exclusion Criteria: - Clinically significant cirrhosis with or without portal hypertension - Glucose-6-phosphate dehydrogenase (G6PD) deficiency - 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

6 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Listed Location Countries ^ICMJE

Removed Location Countries

Administrative Information

Has Data Monitoring Committee

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:

Responsible Party

，

Study Sponsor ^ICMJE

Vertex Pharmaceuticals Incorporated

Collaborators ^ICMJE

Investigators ^ICMJE

PRS Account

Verification Date

September 2018

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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