Study of Lumacaftor in Combination With Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

NCT01897233 | Completed Phase 3 Results

• 1 other identifier: VX13-809-011
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 20

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (4)

• Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 1

  4 hours post-morning dose on Day 1

• Part A: Observed Plasma Concentration of Lumacaftor (LUM) and Ivacaftor (IVA) at Hour 4 Post-dose (C4h) on Day 14

  4 hours post-morning dose on Day 14

• Part A: Area Under the Plasma Concentration-Time Curve From Time 0 to End of Dosing Interval (AUCtau) of Lumacaftor (LUM) and Ivacaftor (IVA)

  The AUCtau is the area under the concentration versus time curve from time 0 to time tau, where tau is the time at the end of dosing interval.

  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)

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

  AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first study drug dose to Week 26 were considered treatment-emergent.

  Day 1 up to Week 26

Secondary Outcomes (13)

• 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

  Day 1, Day 14

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

  Day 1 up to Day 28

• Part B: Average Absolute Change From Baseline in Sweat Chloride at Day 15 and at Week 4

  Baseline, Day 15 and Week 4

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

  Week 24, Week 26

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

  Baseline, Week 24

Study Arms (1)

Lumacaftor/Ivacaftor (LUM/IVA)

EXPERIMENTAL

Part A Cohort 1: Participants aged 6 through 8 years will receive LUM 200 milligram (mg) in fixed-dose combination with IVA 250 mg orally every 12 hours (q12h) for 14 days. Part A Cohort 2: Participants aged 9 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 14 days. Part B: Participants aged 6 through 11 years will receive LUM 200 mg in fixed-dose combination with IVA 250 mg orally q12h for 24 weeks.

Drug: Lumacaftor; Drug: Ivacaftor

Interventions

Lumacaftor DRUG

Also known as: VX-809

Lumacaftor/Ivacaftor (LUM/IVA)

Ivacaftor DRUG

Also known as: VX-770

Lumacaftor/Ivacaftor (LUM/IVA)

Eligibility Criteria

• Age: 6 Years - 11 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (20)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Tucson, Arizona, United States

Location

Unknown Facility

Long Beach, California, United States

Location

Unknown Facility

Palo Alto, California, United States

Location

Unknown Facility

Aurora, Colorado, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Unknown Facility

Boston, Massachusetts, United States

Location

Unknown Facility

Kansas City, Missouri, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Buffalo, New York, United States

Location

Unknown Facility

Rochester, New York, United States

Location

Unknown Facility

Syracuse, New York, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Unknown Facility

Austin, Texas, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Norfolk, Virginia, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Milwaukee, Wisconsin, United States

Location

Unknown Facility

Toronto, Ontario, Canada

Location

Related Publications (4)

• 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.

  PMID: 8474788 BACKGROUND

• Heneghan M, 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. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.

  PMID: 37983082 DERIVED

• 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.

  PMID: 33331662 DERIVED

• 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.

  PMID: 27805836 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor; ivacaftor

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Due to limited sampling and instances of missing data, C4h was reported instead of Cmax as an approximation of maximum concentration. Sparse PK sampling scheme was optimized around parent compounds which limited the estimation of AUC for metabolites.

Results Point of Contact

• Title: Medical Monitor
• Organization: Vertex Pharmaceuticals Incorporated

medicalinfo@vrtx.com

617-341-6777

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: July 1, 2013
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: June 20, 2017
• Results First Posted: December 5, 2016

Record last verified: 2017-05

Locations

US (19); CA (1)