Clinical trial NCT02797132: Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Keywords: CF
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2016-06-13
Enrollment: 62
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Part A: Pre-dose Concentration (Ctrough) of LUM and IVA
timeFrame: Day 15
measure: Part B: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Week 26
Secondary outcomes:
measure: Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites
timeFrame: Day 15
measure: Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 25
measure: Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Weight at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Stature (Height) at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Stature-for-Age Z-Score
timeFrame: Baseline, Week 24
measure: Part B: Number of Pulmonary Exacerbations
timeFrame: Through Week 24
measure: Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24
timeFrame: Through Week 24
measure: Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations
timeFrame: Through Week 24
measure: Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24
timeFrame: Baseline, Through Week 24
measure: Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24
timeFrame: Baseline and Week 24
measure: Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26
timeFrame: Week 24, Week 26
measure: Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale
timeFrame: Day 1
measure: Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites
timeFrame: Week 24
Other outcomes:
Locations:
city: Palo Alto
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Minneapolis
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Buffalo
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Philadelphia
country: United States
state: Pennsylvania
city: Charleston
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: Norfolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Vancouver
country: Canada
state: British Columbia
city: Toronto
country: Canada
state: Ontario
city: Montréal
country: Canada
Study officials:
References:
citation: McNamara JJ, McColley SA, Marigowda G, Liu F, Tian S, Owen CA, Stiles D, Li C, Waltz D, Wang LT, Sawicki GS. Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study. Lancet Respir Med. 2019 Apr;7(4):325-335. doi: 10.1016/S2213-2600(18)30460-0. Epub 2019 Jan 24.