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A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

Primary Purpose

Cystic Fibrosis

Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
LUM/IVA
LUM/IVA
Placebo
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 - 5 Years (Child)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

  • Subjects with confirmed diagnosis of CF.
  • Homozygous for F508del (F/F).
  • Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit.

Key Exclusion Criteria:

  • Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject.
  • Solid organ or hematological transplantation.
  • History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study.

Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • Charite Paediatric Pulmonology Department
  • Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
  • Hannover Medical School
  • Heidelberg Cystic Fibrosis Center
  • Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Part 1: Placebo

Part 1: LUM/IVA

Part 2: Overall LUM/IVA

Arm Description

Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks.

Participants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks.

Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks.

Outcomes

Primary Outcome Measures

Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = <50% of lobe involved and 2 = >=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.

Secondary Outcome Measures

Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48
LCI2.5 represents the number of lung turnovers required to reduce the end-tidal inert gas concentration to 1/40th of its starting value.
Part 1: Absolute Change in Weight-for-age Z-score at Week 48
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Part 1: Absolute Change in Stature-for-age Z-score at Week 48
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48
BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.

Full Information

First Posted
August 7, 2018
Last Updated
October 6, 2022
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT03625466
Brief Title
A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
Official Title
An Exploratory Phase 2, 2-part, Randomized, Double-blind, Placebo-controlled Study With a Long-term, Open-label Period to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
August 10, 2018 (Actual)
Primary Completion Date
October 9, 2020 (Actual)
Study Completion Date
October 7, 2021 (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

5. Study Description

Brief Summary
This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).

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 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double blinded in Part 1, and Open label in Part 2
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks.
Arm Title
Part 1: LUM/IVA
Arm Type
Experimental
Arm Description
Participants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks.
Arm Title
Part 2: Overall LUM/IVA
Arm Type
Experimental
Arm Description
Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
Lumacaftor/Ivacaftor, VX-809/VX-770
Intervention Description
FDC tablets or granules for oral administration.
Intervention Type
Drug
Intervention Name(s)
LUM/IVA
Other Intervention Name(s)
Lumacaftor/Ivacaftor, VX-809/VX-770
Intervention Description
FDC granules for oral administration.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo matched to LUM/IVA for oral administration.
Primary Outcome Measure Information:
Title
Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48
Description
MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = <50% of lobe involved and 2 = >=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement.
Time Frame
From Baseline at Week 48
Secondary Outcome Measure Information:
Title
Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48
Description
LCI2.5 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 Baseline Through Week 48
Title
Part 1: Absolute Change in Weight-for-age Z-score at Week 48
Description
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time Frame
From Baseline at Week 48
Title
Part 1: Absolute Change in Stature-for-age Z-score at Week 48
Description
The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time Frame
From Baseline at Week 48
Title
Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48
Description
BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard.
Time Frame
From Baseline at Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Subjects with confirmed diagnosis of CF. Homozygous for F508del (F/F). Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit. Key Exclusion Criteria: Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject. Solid organ or hematological transplantation. History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study. Other protocol defined Inclusion/Exclusion criteria may apply.
Facility Information:
Facility Name
Charite Paediatric Pulmonology Department
City
Berlin
Country
Germany
Facility Name
Justus-Leibig-Universitat Zentrum fur Kinderheilkunde und Jugendmedizin
City
Giessen
Country
Germany
Facility Name
Hannover Medical School
City
Hannover
Country
Germany
Facility Name
Heidelberg Cystic Fibrosis Center
City
Heidelberg
Country
Germany
Facility Name
Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
City
Lubeck
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

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