Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor

A Phase 3, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Lumacaftor in Combination With Ivacaftor in Subjects Aged 6 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Study 110 is a Phase 3, multicenter study in subjects aged 6 years and older with cystic fibrosis (CF) who are homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation and who participated in Study 109 (NCT02514473) or Study 011B (NCT01897233). Study 110 is designed to evaluate the safety and efficacy of long term treatment of lumacaftor in combination with ivacaftor.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: LUM/IVA; Drug: LUM/IVA

• Study Type: Interventional
• Enrollment (Actual): 246
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia
  • New Lambton Heights, Australia
  • Subiaco, Australia
  • Westmead, Australia
  • Victoria
    • Parkville, Victoria, Australia
• Belgium
  • Brussels, Belgium
  • Leuven, Belgium
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• Denmark
  • Copenhagen, Denmark
• France
  • Bordeaux Cedex, France
  • Paris, France
  • Paris Cedex 15, France
  • Cedex
    • Bron, Cedex, France
• Germany
  • Berlin, Germany
  • Giessen, Germany
  • Hanover, Germany
  • Koeln, Germany
• Sweden
  • Stockholm, Sweden
• United Kingdom
  • Belfast, United Kingdom
  • Edinburgh, United Kingdom
  • London, United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom
• United States
  • Alabama
    • Birmingham, Alabama, United States
  • Arizona
    • Tucson, Arizona, United States
  • California
    • Long Beach, California, United States
    • Palo Alto, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Delaware
    • Wilmington, Delaware, United States
  • Florida
    • Jacksonville, Florida, United States
    • Orlando, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Iowa
    • Iowa City, Iowa, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Minnesota
    • Minneapolis, Minnesota, United States
  • Missouri
    • Kansas City, Missouri, United States
    • Saint Louis, Missouri, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New Hampshire
    • Lebanon, New Hampshire, United States
  • New York
    • Buffalo, New York, United States
    • Syracuse, New York, United States
  • North Carolina
    • Chapel Hill, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Cleveland, Ohio, United States
    • Dayton, Ohio, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Texas
    • Austin, Texas, United States
    • Houston, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States
  • Vermont
    • Colchester, Vermont, United States
  • Virginia
    • Charlottesville, Virginia, United States
    • Norfolk, Virginia, United States
    • Richmond, Virginia, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Madison, Wisconsin, United States
    • Milwaukee, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects entering the Treatment Cohort must meet both of the following criteria:

• Completed study visits up to Week 24 of Study 109 or Week 26 of Study 011B and did not permanently discontinue treatment
• Willing to remain on a stable CF medication through the Safety Follow-up Visit.

Subjects entering the Observational Cohort must meet 1 of the following criteria:

• Completed 24 weeks of study drug treatment in Study 109 or completed 24 weeks of study drug treatment and the Week 26 Safety Follow up in Study 011B.
• Received at least 4 weeks of study drug and completed visits up to Week 24 of Study 109 or Week 26 of Study 011B.

Exclusion Criteria (Treatment Cohort Only):

• History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject (e.g., cirrhosis with portal hypertension).
• Pregnant and nursing females.
• Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
• History of drug intolerance in the prior study that would pose an additional risk to the subject in the opinion of investigator
• History of poor compliance with study drug and/or procedure in the previous study as deemed by the investigator.
• Participation in an investigational drug trial (including studies investigating lumacaftor and/or ivacaftor).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Period 1: LUM/IVA to LUM/IVA	Drug: LUM/IVA; Lumacaftor (LUM) 200 mg every 12 hours (q12h)/ivacaftor (IVA) 250 mg q12h (for 6 through 11 years of age). LUM 400 mg q12h/IVA 250 mg q12h (for 12 years and older).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770; Drug: LUM/IVA; LUM 200 mg q12h/IVA 250 mg q12h (for 6 through 11 years of age).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770
Experimental: Treatment Period 1: Placebo (PBO) to LUM/IVA	Drug: LUM/IVA; Lumacaftor (LUM) 200 mg every 12 hours (q12h)/ivacaftor (IVA) 250 mg q12h (for 6 through 11 years of age). LUM 400 mg q12h/IVA 250 mg q12h (for 12 years and older).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770; Drug: LUM/IVA; LUM 200 mg q12h/IVA 250 mg q12h (for 6 through 11 years of age).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770
No Intervention: Treatment Period 1: Observational Cohort
Experimental: Treatment Period 2: LUM/IVA	Drug: LUM/IVA; Lumacaftor (LUM) 200 mg every 12 hours (q12h)/ivacaftor (IVA) 250 mg q12h (for 6 through 11 years of age). LUM 400 mg q12h/IVA 250 mg q12h (for 12 years and older).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770; Drug: LUM/IVA; LUM 200 mg q12h/IVA 250 mg q12h (for 6 through 11 years of age).; Other Names: lumacaftor/ivacaftor; VX-809/VX-770

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment Period 1 (Treatment Cohorts): Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Lung Clearance Index (LCI) 2.5	LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.	From Parent Study Baseline at Week 96
Absolute Change in Sweat Chloride	Sweat samples were collected using an approved collection device.	From Parent Study Baseline at Week 96
Absolute Change in Body Mass Index (BMI)	BMI was defined as weight in kilograms divided by height in square meter (m^2).	From Parent Study Baseline at Week 96
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score	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.	From Parent Study Baseline at Week 96
Observational Cohort: Safety as Assessed by Serious Adverse Events (SAEs)		Day 1 up to Week 100
Absolute Change in LCI 5.0	LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.	From Parent Study Baseline at Week 96
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 Parent Study Baseline at Week 96
Relative Change in ppFEV1	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	From Parent Study Baseline at Week 96
Absolute Change in BMI-for-age Z-score	BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. 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.	From Parent Study Baseline at Week 96
Absolute Change in Weight		From Parent Study Baseline at Week 96
Absolute Change in Weight-for-age Z-score	z-score is a statistical measure to describe whether a mean was above or below the standard. 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.	From Parent Study Baseline at Week 96
Absolute Change in Height		From Parent Study Baseline at Week 96
Absolute Change in Height-for-age Z-score	z-score is a statistical measure to describe whether a mean was above or below the standard. 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.	From Parent Study Baseline at Week 96
Absolute Change in Treatment Satisfaction Questionnaire for Medication (TSQM) Total Domain Score	The TSQM measures participants' experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. For each dimension, responses are added and transformed in the total domain score, which ranges from 0 to 100, where higher scores indicate greater satisfaction.	From Parent Study Baseline at Week 96
Time-to-first Pulmonary Exacerbation	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.	From Parent Study Baseline through Week 96
Percentage of Participants Having At Least 1 Pulmonary Exacerbation Event	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.	From Parent Study Baseline through Week 96
Number of Pulmonary Exacerbation Events Per Patient-year	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.	From Parent Study Baseline through Week 96
Rate of Change in LCI 2.5	Rate of change analysis evaluates the change in LCI 2.5 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.	Day 15 after first dose of LUM/IVA through Week 96
Rate of Change in LCI 5.0	Rate of change analysis evaluates the change in LCI 5.0 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.	Day 15 after first dose of LUM/IVA through Week 96
Rate of Change in ppFEV1	Rate of change analysis evaluates the change in ppFEV1 after long term treatment with LUM/IVA. A rate of change equal to zero would indicate that treatment effects were stable.	Day 15 after first dose of LUM/IVA through Week 96
Treatment Period 2: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)		Day 1 up to Week 168

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Chilvers MA, Davies JC, Milla C, Tian S, Han Z, Cornell AG, Owen CA, Ratjen F. Long-term safety and efficacy of lumacaftor-ivacaftor therapy in children aged 6-11 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a phase 3, open-label, extension study. Lancet Respir Med. 2021 Jul;9(7):721-732. doi: 10.1016/S2213-2600(20)30517-8. Epub 2021 Jan 28. Erratum In: Lancet Respir Med. 2021 Apr;9(4):e38.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): April 1, 2020

Study Registration Dates

• First Submitted: September 1, 2015
• First Submitted That Met QC Criteria: September 4, 2015
• First Posted (Estimate): September 9, 2015

Study Record Updates

• Last Update Posted (Actual): May 24, 2021
• Last Update Submitted That Met QC Criteria: April 27, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX15-809-110