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

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
LUM/IVA
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University
  • Children's Hospital Colorado
  • Ann & Robert Lurie Children's Hospital of Chicago
  • Riley Hospital for Children at Indiana University Health
  • Boston Children's Hospital
  • Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
  • Children's Mercy Hospital
  • The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo
  • University of North Carolina Hospitals
  • Cincinnati Children's Hospital Medical Center
  • University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
  • Nationwide Children's Hospital
  • Children's Hospital of Philadelphia
  • Medical University of South Carolina
  • Texas Children's Hospital
  • Children's Hospital of the King's Daughters
  • Seattle Children's Hospital
  • British Columbia's Children's Hospital
  • The Hospital for Sick Children
  • McGill University Health Centre, Glen Site, Montreal Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LUM/IVA

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Absolute Change in Sweat Chloride
Sweat samples were collected using an approved collection device.
Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
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.
Absolute Change in Weight
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.
Absolute Change From Baseline in Stature (Height)
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.
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.
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.
Number of Cystic Fibrosis (CF) Related Hospitalizations
Absolute Change in Fecal Elastase-1 (FE-1) Levels
Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
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.
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.
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.

Full Information

First Posted
April 19, 2017
Last Updated
July 15, 2020
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03125395
Brief Title
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Completed
Study Start Date
May 12, 2017 (Actual)
Primary Completion Date
July 17, 2019 (Actual)
Study Completion Date
July 17, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LUM/IVA
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
VX-809/VX-770, lumacaftor/ivacaftor
Intervention Description
Participants received LUM/IVA every q12h.
Primary Outcome Measure Information:
Title
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
Day 1 up to Week 98
Secondary Outcome Measure Information:
Title
Absolute Change in Sweat Chloride
Description
Sweat samples were collected using an approved collection device.
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Body Mass Index (BMI)
Description
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in BMI-for-age Z-score
Description
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.
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Weight
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Weight-for-age Z-score
Description
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.
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change From Baseline in Stature (Height)
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Stature-for-age Z-score
Description
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.
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Time-to-first Pulmonary Exacerbation
Description
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
Time Frame
From Parent Study 115B Baseline through Week 96
Title
Number of Pulmonary Exacerbations (PEx)
Description
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
Time Frame
From Parent Study 115B Baseline through Week 96
Title
Number of Cystic Fibrosis (CF) Related Hospitalizations
Time Frame
From Parent Study 115B Baseline through Week 96
Title
Absolute Change in Fecal Elastase-1 (FE-1) Levels
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Number of Participants With Microbiology Culture Status (Positive or Negative)
Description
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.
Time Frame
Week 96
Title
Absolute Change in Lung Clearance Index (LCI) 2.5
Description
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.
Time Frame
From Parent Study 115B Baseline at Week 96
Title
Absolute Change in Lung Clearance Index (LCI) 5.0
Description
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.
Time Frame
From Parent Study 115B Baseline at Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Ann & Robert Lurie Children's Hospital of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Riley Hospital for Children at Indiana University Health
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo
City
Buffalo
State/Province
New York
ZIP/Postal Code
14222
Country
United States
Facility Name
University of North Carolina Hospitals
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
British Columbia's Children's Hospital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6H 3N1
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1X8
Country
Canada
Facility Name
McGill University Health Centre, Glen Site, Montreal Children's Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H4A 3J1
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
33965000
Citation
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.
Results Reference
derived

Learn more about this trial

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

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