A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • British Columbia's Children's Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre, Glen Site, Montreal Children's Hospital
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children at Indiana University Health
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • Buffalo, New York, United States, 14222
      • The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Hospitals
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects entering the Treatment Cohort must meet the following criteria:

• Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)
• Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit

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

• Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.
• Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.
• Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.

Exclusion Criteria (Treatment Cohort Only):

• Prematurely discontinued LUM/IVA treatment in Study 115B.
• 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 LUM/IVA to the subject
• History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.
• Subjects with a history of allergy or hypersensitivity to LUM/IVA.
• Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.
• QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor
• History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator.
• Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LUM/IVA; LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age.	Drug: LUM/IVA; Participants received LUM/IVA every q12h.; Other Names: lumacaftor/ivacaftor; VX-809/VX-770

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Day 1 up to Week 98

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change in Sweat Chloride	Sweat samples were collected using an approved collection device.	From Parent Study 115B Baseline at Week 96
Absolute Change in Body Mass Index (BMI)	BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).	From Parent Study 115B 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 115B Baseline at Week 96
Absolute Change in Weight		From Parent Study 115B 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 115B Baseline at Week 96
Absolute Change From Baseline in Stature (Height)		From Parent Study 115B Baseline at Week 96
Absolute Change in Stature-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 115B Baseline at Week 96
Time-to-first Pulmonary Exacerbation	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.	From Parent Study 115B Baseline through Week 96
Number of Pulmonary Exacerbations (PEx)	Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.	From Parent Study 115B Baseline through Week 96
Number of Cystic Fibrosis (CF) Related Hospitalizations		From Parent Study 115B Baseline through Week 96
Absolute Change in Fecal Elastase-1 (FE-1) Levels		From Parent Study 115B Baseline at Week 96
Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels		From Parent Study 115B Baseline at Week 96
Number of Participants With Microbiology Culture Status (Positive or Negative)	Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.	Week 96
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 115B Baseline at Week 96
Absolute Change in Lung Clearance Index (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 115B Baseline at Week 96

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• Hoppe JE, Chilvers M, Ratjen F, McNamara JJ, Owen CA, Tian S, Zahigian R, Cornell AG, McColley SA. Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. 2021 Sep;9(9):977-988. doi: 10.1016/S2213-2600(21)00069-2. Epub 2021 May 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 12, 2017
• Primary Completion (ACTUAL): July 17, 2019
• Study Completion (ACTUAL): July 17, 2019

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 21, 2017
• First Posted (ACTUAL): April 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

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: VX16-809-116; 2019-003112-31 (EUDRACT_NUMBER)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No