Clinical trial NCT01897233: Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Official title: A Phase 3, Open-label Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2013-07-11
Enrollment: 62
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
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 to evaluate the pharmacokinetics, safety, and tolerability of lumacaftor in combination with ivacaftor in subjects with cystic fibrosis aged 6 to 11 years who have the F508del-mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of CF defined as: with 2 CF-causing mutations, chronic sinopulmonary disease or gastrointestinal/nutritional abnormalities
* Subjects who weigh ≥15 kg without shoes at Screening Visit
* Subjects who are homozygous for the F508del-CFTR mutation
* Subjects with percent predicted forced expiratory volume in 1 second (FEV1) of 70% to 105% (inclusive) (Part A) or ≥40% (Part B) at Screening Visit where the predicted values are adjusted for age, sex, and height using the Wang equation
* Subjects with stable CF disease and who are willing to remain on stable CF medication regimen
* Able to swallow tablets

Exclusion Criteria:

* History of any illness or condition that might confound the results of the study or pose an additional risk in administering study drug to the subject
* Acute respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before Day 1 of the study
* Abnormal liver function as defined in the protocol at Screening Visit
* Abnormal renal function as defined in the protocol at Screening Visit
* History of solid organ or hematological transplantation
* Ongoing participation in an investigational drug study or prior participation in an investigational drug study within 30 days prior of Screening Visit
* History or evidence of lens opacity or cataract at Screening Visit
* Colonization with organisms associated with a more rapid decline in pulmonary status at Screening Visit (Part A only)
* A standard 12-lead ECG demonstrating QTcF \>450 msec at Screening Visit

Primary outcomes:
measure: Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1
timeFrame: 4 hours post-morning dose on Day 1
measure: Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14
timeFrame: 4 hours post-morning dose on Day 14
measure: Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA)
timeFrame: Day 14 (pre-morning dose, 4, 6, 12, and 24 hours post-morning dose for LUM; pre-morning dose, 2, 4, 6, 12 hours post-morning dose for IVA)
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: Observed Plasma Concentration of Lumacaftor Metabolite (M28-LUM) and Ivacaftor Metabolites (M1-IVA and M6-IVA) at Hour 4 Post-dose (C4h) on Day 1 and 14
timeFrame: Day 1, Day 14
measure: Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Day 1 up to Day 28
measure: Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4
timeFrame: Baseline, Day 15 and Week 4
measure: Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26
timeFrame: Week 24, Week 26
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 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 Height at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Height-for-age Z-score at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Absolute Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM) Domains at Week 24
timeFrame: Baseline, Week 24
measure: Part B: Pre-dose Concentration (Ctrough) and 3 to 6 Hours Post-dose Concentration (C3-6hr) of Lumacaftor, Lumacaftor Metabolite (M28-LUM), Ivacaftor and Ivacaftor Metabolites (M1-IVA and M6-IVA)
timeFrame: For Ctrough: pre-morning dose on Week 4, Week 6 and Week 24; For C3-6hr: 3 to 6 hours post-morning dose on Day 1, 15 and Week 4
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tucson
country: United States
state: Arizona
city: Long Beach
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Boston
country: United States
state: Massachusetts
city: Kansas City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Buffalo
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Syracuse
country: United States
state: New York
city: Charleston
country: United States
state: South Carolina
city: Austin
country: United States
state: Texas
city: Salt Lake City
country: United States
state: Utah
city: Norfolk
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Milwaukee
country: United States
state: Wisconsin
city: Toronto
country: Canada
state: Ontario
Study officials:
References:
citation: Wang X, Dockery DW, Wypij D, Fay ME, Ferris BG Jr. Pulmonary function between 6 and 18 years of age. Pediatr Pulmonol. 1993 Feb;15(2):75-88. doi: 10.1002/ppul.1950150204.
citation: Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
citation: Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M; VX13-809-011 Part B Investigator Group *. Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2017 Apr 1;195(7):912-920. doi: 10.1164/rccm.201608-1754OC.