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Completed

NCT Number: NCT02797132

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

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.

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Key information

Conditions

Cystic Fibrosis Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Infant, Newborn, Diseases Lung Diseases Pancreatic Diseases Respiratory Tract Diseases

Age range

2 year–5 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Vancouver, British Columbia, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

LUM/IVA

Drug

Other names: Orkambi, VX-809+VX-770

Primary outcomes

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

    Time frame: Day 15

  2. 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

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

    Time frame: Day 15

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

    Time frame: Day 1 up to Day 25

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

    Time frame: Baseline, Week 24

    Sweat samples were collected using an approved collection device.

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

    Time frame: Baseline, Week 24

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

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

    Time frame: Baseline, 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).

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, 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).

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Week 24

    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).

  10. Part B: Number of Pulmonary Exacerbations

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: Through Week 24

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

    Time frame: Baseline, Week 24

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

    Time frame: Baseline, Through Week 24

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

    Time frame: Baseline and 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.

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

    Time frame: Baseline, Week 24

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

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

    Time frame: Week 24, Week 26

    Sweat samples were collected using an approved collection device.

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

    Time frame: Day 1

    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).

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

    Time frame: Baseline, 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.

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

    Time frame: Baseline, 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.

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

    Time frame: Week 24

Sponsors and collaborators

Lead sponsor

Vertex Pharmaceuticals Incorporated

Industry

Registry information

Official study title

A Phase 3, 2-Part, Open-label Study to Evaluate the Safety and Pharmacokinetics of Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Jun 13, 2016
Registry last updated
Oct 30, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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