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Completed

NCT Number: NCT03525444

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)

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).

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

12 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Women & Children's Hospital, North Adelaide, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key 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

Treatment and study plan

VX-445/TEZ/IVA

Drug

Participants received VX-445/TEZ/IVA orally once daily in the morning.

Other names: VX-445/VX-661/VX-770, VX-445/tezacaftor/ivacaftor

IVA

Drug

Participants received IVA orally once daily in the evening

Other names: VX-770, ivacaftor

Placebo

Drug

Participants received placebo matched VX-445/TEZ/IVA orally once daily in the morning and placebo matched to IVA orally once daily in the evening.

Primary outcomes

  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline at Week 4

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Secondary outcomes

  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

    Time frame: From Baseline through Week 24

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

  2. Number of Pulmonary Exacerbations (PEx)

    Time frame: 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.

  3. Absolute Change in Sweat Chloride (SwCl)

    Time frame: From Baseline through Week 24

    Sweat samples were collected using an approved collection device.

  4. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score

    Time frame: From Baseline through Week 24

    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.

  5. Absolute Change in Body Mass Index (BMI)

    Time frame: From Baseline at Week 24

    BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

  6. Absolute Change in Sweat Chloride

    Time frame: From Baseline at Week 4

    Sweat samples were collected using an approved collection device.

  7. Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score

    Time frame: 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.

  8. Time-to-first Pulmonary Exacerbation (PEx)

    Time frame: 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.

  9. Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline

    Time frame: 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.

  10. Absolute Change in Body Weight

    Time frame: From Baseline at Week 24

  11. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: 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)

  12. Observed Pre-dose Concentration (Ctrough) of VX-445, TEZ, M1-TEZ, and IVA

    Time frame: Pre-dose on Week 4, 8, 12, and 16

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Registry information

Official study title

A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
May 15, 2018
Registry last updated
May 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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