Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

Vertex Pharmaceuticals Incorporated62 enrolled

Overview

This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cystic Fibrosis

Interventions

LUM/IVADRUG

Eligibility

Sex: ALLMin age: 2 YearsMax age: 5 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit * Subjects with confirmed diagnosis of CF at the Screening Visit * Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation 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 * An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 * A standard 12-lead ECG demonstrating QTc \>450 millisecond (msec) at the Screening Visit. * History of solid organ or hematological transplantation. * Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit. * History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit

Locations (20)

Unnamed facility

Palo Alto, California, United States

Unnamed facility

Aurora, Colorado, United States

Unnamed facility

Chicago, Illinois, United States

Outcomes

Primary Outcomes

Part A: Pre-dose Concentration (Ctrough) of LUM and IVA

Time frame: Day 15

Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 up to Week 26

Secondary Outcomes

Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites

Time frame: Day 15

Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time frame: Day 1 up to Day 25

Part B: Absolute Change From Baseline in Sweat Chloride at Week 24

Sweat samples were collected using an approved collection device.

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24

BMI was defined as weight in kilograms (kg) divided by height in square meter (m\^2).

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24

BMI was defined as weight in kg divided by height in m\^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Weight at Week 24

Time frame: Baseline, Week 24

Data from ClinicalTrials.gov

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Unnamed facility

Indianapolis, Indiana, United States

Unnamed facility

Boston, Massachusetts, United States

Unnamed facility

Minneapolis, Minnesota, United States

Unnamed facility

Kansas City, Missouri, United States

Unnamed facility

Buffalo, New York, United States

Unnamed facility

Chapel Hill, North Carolina, United States

Unnamed facility

Cincinnati, Ohio, United States

...and 10 more locations

Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24

z-score is a statistical measure to describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (Weight z-score).

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Stature (Height) at Week 24

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Stature-for-Age Z-Score

z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score).

Time frame: Baseline, Week 24

Part B: Number of Pulmonary Exacerbations

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: Through Week 24

Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24

Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.

Time frame: Through Week 24

Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations

Time frame: Through Week 24

Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24

Time frame: Baseline, Week 24

Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24

Time frame: Baseline, Through Week 24

Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24

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: Baseline and Week 24

Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Time frame: Baseline, Week 24

Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26

Sweat samples were collected using an approved collection device.

Time frame: Week 24, Week 26

Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale

The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2).

Time frame: Day 1

Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24

Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). 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: Baseline, Week 24

Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24

LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). 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: Baseline, Week 24

Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites

Time frame: Week 24