A Phase 3 Study of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

Phase 3

Completed

• Conditions: Cystic Fibrosis
• Interventions: Drug: Placebo; Drug: VX-445/TEZ/IVA; Drug: IVA

• Registration Number: NCT03525444
• Lead Sponsor: Vertex Pharmaceuticals Incorporated

Brief Summary

This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function mutation (F/MF subjects).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-05-02
• Study First Submitted QC: 2018-05-02
• Study First Posted: 2018-05-15
• Study Start: 2018-06-15
• Primary Completion: 2019-04-24
• Study Completion: 2019-04-24
• Results First Submitted: 2020-04-22
• Status Verified: 2020-05
• Results First Submitted QC: 2020-05-06
• Last Update Submitted: 2020-05-06
• Results First Posted: 2020-05-19
• Last Update Posted: 2020-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 405

Inclusion Criteria

• Heterozygous for the F508del mutation (F/MF)
• Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants who received placebo matched to VX-445/TEZ/IVA for 24 weeks in the TC treatment period.
VX-445/TEZ/IVA TC	IVA	Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
VX-445/TEZ/IVA TC	VX-445/TEZ/IVA	Participants who received VX-445 200 mg/TEZ 100 mg/IVA150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.

Primary Outcome Measures

Name	Time	Method
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline at Week 4	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in Sweat Chloride (SwCl)	From Baseline through Week 24	Sweat samples were collected using an approved collection device.
Number of Pulmonary Exacerbations (PEx)	From Baseline through Week 24	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time-to-first Pulmonary Exacerbation (PEx)	From Baseline through Week 24	Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Absolute Change in Body Weight	From Baseline at Week 24
Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score	From Baseline at Week 4	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Absolute Change in Sweat Chloride	From Baseline at Week 4	Sweat samples were collected using an approved collection device.
Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline	From Baseline at Week 24	BMI was defined as weight in kg divided by height in m\^2. Z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	From Baseline through Week 24	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Body Mass Index (BMI)	From Baseline at Week 24	BMI was defined as weight in kilogram (kg) divided by height in square meter (m\^2).
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 28 weeks)
Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA	Pre-dose on Week 4, 8, 12, and 16

Trial Locations

Locations (115)

Banner University of Arizona Medical Center; 🇺🇸 Tucson, Arizona, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Miller Children's Hospital/ Long Beach Memorial; 🇺🇸 Long Beach, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Valley Children's Hospital/ Children's Hospital of Central California; 🇺🇸 Madera, California, United States

Kaiser Permanente; 🇺🇸 Oakland, California, United States

University of California Davis Medical Center; 🇺🇸 Sacramento, California, United States

UCSF Gateway Medical Center; 🇺🇸 San Francisco, California, United States

National Jewish Health; 🇺🇸 Denver, Colorado, United States

University of Florida, Shands Hospital; 🇺🇸 Gainesville, Florida, United States

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