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Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease

Primary Purpose

Cystic Fibrosis, Advanced Lung Disease

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Lumacaftor
Ivacaftor
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

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

Inclusion Criteria:

  • Homozygous for the F508del-CFTR mutation; historical genotype must be documented in the participant's source documents.
  • Percent predicted FEV1 <40 of adjusted for age, sex, and height at Screening

Exclusion Criteria:

  • Participant currently receiving invasive mechanical ventilation.
  • History of any comorbidity 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 participant
  • Any clinically significant laboratory abnormalities at screening that would interfere with the study assessments or pose an undue risk for the subject
  • A 12-lead electrocardiograms (ECG) demonstrating QTcF >450 msec at Screening
  • History of solid organ or hematological transplantation
  • History of alcohol or drug abuse in the past year
  • Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening.
  • Use of strong inhibitors, moderate inducers, or strong inducers of CYP3A
  • Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1.
  • Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements
  • Use of beta blockers or the equivalent at Screening.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lumacaftor/Ivacaftor combination

Arm Description

Lumacaftor 400 milligram (mg) and ivacaftor 250 mg combination tablet orally twice daily for 24 weeks.

Outcomes

Primary Outcome Measures

Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; event does not necessarily have a causal relationship with treatment. This includes any newly occurring event/previous condition that has increased in severity/frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs: AEs that started/ worsened on/after the start of study drug through the Safety Follow up Visit (4 weeks after the last dose of study drug). Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Secondary Outcome Measures

Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Duration For Which Participants Received Intravenous (IV) Antibiotics
The duration for which participants received IV antibiotics for sinopulmonary signs and symptoms were reported. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Number of Hospitalizations
Number of hospitalizations (all causes) through Week 24 was summarized. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Absolute Change From Baseline in Sweat Chloride at Average of Day 15 and Week 4
Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. The average absolute change from baseline in sweat chloride was derived as: (Average of Day 15 and Week 4 value) minus Baseline value. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score 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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.

Full Information

First Posted
March 11, 2015
Last Updated
October 31, 2017
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT02390219
Brief Title
Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease
Official Title
A Phase 3b, Open-Label Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Cystic Fibrosis and Advanced Lung Disease, Homozygous for the F508del-CFTR Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
March 2015 (undefined)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety and tolerability of LUM/IVA combination therapy in subjects 12 years and older with CF and advanced lung disease and who are homozygous for the F508del CFTR mutation

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Lumacaftor/Ivacaftor combination
Arm Type
Experimental
Arm Description
Lumacaftor 400 milligram (mg) and ivacaftor 250 mg combination tablet orally twice daily for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Lumacaftor
Other Intervention Name(s)
VX-809
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
VX-770
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
Description
AE: any untoward medical occurrence in a participant during the study; event does not necessarily have a causal relationship with treatment. This includes any newly occurring event/previous condition that has increased in severity/frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event, which falls into any of the following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. TEAEs: AEs that started/ worsened on/after the start of study drug through the Safety Follow up Visit (4 weeks after the last dose of study drug). Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Day 1 up to Week 28
Secondary Outcome Measure Information:
Title
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline, Up to Week 24
Title
Absolute Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Up to Week 24
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate FEV1 (for age, gender, race, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline, Up to Week 24
Title
Duration For Which Participants Received Intravenous (IV) Antibiotics
Description
The duration for which participants received IV antibiotics for sinopulmonary signs and symptoms were reported. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline through Week 24
Title
Number of Hospitalizations
Description
Number of hospitalizations (all causes) through Week 24 was summarized. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline through Week 24
Title
Absolute Change From Baseline in Sweat Chloride at Average of Day 15 and Week 4
Description
Sweat samples were collected using an approved collection device. Baseline was defined as the average of the measurements at screening and on Day 1 pre-dose. The average absolute change from baseline in sweat chloride was derived as: (Average of Day 15 and Week 4 value) minus Baseline value. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline, Day 15 and Week 4
Title
Absolute Change From Baseline in Cystic Fibrosis Questionnaire - Revised (CFQ-R) Respiratory Domain Score Through Week 24
Description
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 (for example, coughing, congestion, wheezing), the scaled score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Results were reported as planned, as a combined single LUM/IVA arm irrespective of permitted dose modification.
Time Frame
Baseline, Through Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Homozygous for the F508del-CFTR mutation; historical genotype must be documented in the participant's source documents. Percent predicted FEV1 <40 of adjusted for age, sex, and height at Screening Exclusion Criteria: Participant currently receiving invasive mechanical ventilation. History of any comorbidity 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 participant Any clinically significant laboratory abnormalities at screening that would interfere with the study assessments or pose an undue risk for the subject A 12-lead electrocardiograms (ECG) demonstrating QTcF >450 msec at Screening History of solid organ or hematological transplantation History of alcohol or drug abuse in the past year Ongoing or prior participation in an investigational drug study (including studies investigating lumacaftor and/or ivacaftor) within 30 days of screening. Use of strong inhibitors, moderate inducers, or strong inducers of CYP3A Pregnant and nursing females: Females of childbearing potential must have a negative pregnancy test at Screening and Day 1. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements Use of beta blockers or the equivalent at Screening.
Facility Information:
City
Denver
State/Province
Colorado
Country
United States
City
Tampa
State/Province
Florida
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
Houston
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
29126871
Citation
Taylor-Cousar JL, Jain M, Barto TL, Haddad T, Atkinson J, Tian S, Tang R, Marigowda G, Waltz D, Pilewski J; VX14-809-106 Investigator Group. Lumacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease homozygous for F508del-CFTR. J Cyst Fibros. 2018 Mar;17(2):228-235. doi: 10.1016/j.jcf.2017.09.012. Epub 2017 Nov 8.
Results Reference
derived

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Study to Evaluate Lumacaftor and Ivacaftor Combination Therapy in Subjects 12 Years and Older With Advanced Lung Disease

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