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

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

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).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 51
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Part 1: Placebo; Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks.	Drug: Placebo; Placebo matched to LUM/IVA for oral administration.
Experimental: Part 1: LUM/IVA; 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.	Drug: LUM/IVA; FDC tablets or granules for oral administration.; Other Names: VX-809/VX-770; Lumacaftor/Ivacaftor; Drug: LUM/IVA; FDC granules for oral administration.; Other Names: VX-809/VX-770; Lumacaftor/Ivacaftor
Experimental: Part 2: Overall LUM/IVA; 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.	Drug: LUM/IVA; FDC tablets or granules for oral administration.; Other Names: VX-809/VX-770; Lumacaftor/Ivacaftor; Drug: LUM/IVA; FDC granules for oral administration.; Other Names: VX-809/VX-770; Lumacaftor/Ivacaftor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline at Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From Baseline Through Week 48
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.	From Baseline at Week 48
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.	From Baseline at Week 48
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.	From Baseline at Week 48

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2018
• Primary Completion (Actual): October 9, 2020
• Study Completion (Actual): October 7, 2021

Study Registration Dates

• First Submitted: August 7, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): November 2, 2022
• Last Update Submitted That Met QC Criteria: October 6, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Disease Progression; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX16-809-121; 2017-003761-99 (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