A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of VX-661/Ivacaftor in Pediatric Subjects With Cystic Fibrosis (CF)

NCT ID: NCT02953314

Last Updated: 2020-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-09-30

Brief Summary

This is a Phase 3, 2-part (Part A and Part B), open label, multicenter study evaluating the pharmacokinetic (PK), safety, and tolerability of multiple doses of tezacaftor (TEZ) in combination with ivacaftor (IVA) in subjects 6 through 11 years of age with CF who are homozygous or heterozygous for the F508del- CF transmembrane conductance regulator protein (CFTR) mutation.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A

Participants weighing <25 kg received TEZ 50 mg once daily/IVA 75 mg q12h orally for 14 days.

Participants weighing ≥25 kg received TEZ 50 mg once daily/IVA 150 mg q12h orally for 14 days.

Group Type: EXPERIMENTAL

TEZ

Intervention Type: DRUG

IVA

Intervention Type: DRUG

Part B

Participants weighing <40 kg received TEZ 50 mg/IVA 75 mg as fixed dose combination orally once daily in the morning and IVA 75 mg orally once daily in the evening for 24 weeks.

Participants weighing ≥40 kg received TEZ 100 mg/IVA 150 mg as fixed dose combination orally once daily in the morning and IVA 150 mg orally once daily in the evening for 24 weeks.

Group Type: EXPERIMENTAL

TEZ/IVA

Intervention Type: DRUG

IVA

Intervention Type: DRUG

Interventions

TEZ

Intervention Type: DRUG

TEZ/IVA

Intervention Type: DRUG

IVA

Intervention Type: DRUG

Other Intervention Names

tezacaftor; VX-661; tezacaftor/ivacaftor; VX-661/VX-770; ivacaftor; VX-770

Eligibility Criteria

Inclusion Criteria

• Subjects who weigh ≥15 kg without shoes at the Screening Visit.
• All genotypes as specified by the study protocol are eligible in Part A.
• The following genotypes are eligible in Part B:

• homozygous for the F508del CFTR mutation
• heterozygous for the F508del CFTR mutation and with a second allele with a CFTR mutation predicted to have residual function.
• heterozygous for the F508del CFTR mutation and with a second CFTR allele with a gating defect that is clinically demonstrated to be ivacaftor responsive
• Subjects with a confirmed diagnosis of CF defined as a sweat chloride value ≥60 mmol/L or chronic sinopulmonary and/or gastrointestinal disease consistent with a diagnosis of CF. Subjects who are homozygous for the F508del-CFTR mutation must have a sweat chloride value ≥60 mmol/L.
• Subjects with ppFEV1 of ≥40 percentage points at the Screening Visit
• Subjects with stable CF disease as deemed by the investigator at the Screening Visit.
• Subjects who are willing to remain on their stable CF medication regimen through Day 14 (Part A) or through Week 24 (Part B) or, if applicable, through the Safety Follow up Visit.
• Subjects who are able to swallow tablets.
• Female subjects of childbearing potential must have a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at the Day 1 Visit before receiving the first dose of study drug.
• Subjects of childbearing potential who are sexually active must meet the contraception requirements

Exclusion Criteria

• History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
• 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 for pulmonary disease within 28 days before Day 1
• Colonization with organisms associated with a more rapid decline in pulmonary status.
• A standard 12 lead ECG demonstrating QTc >450 msec at the Screening Visit.
• History of solid organ or hematological transplantation at the Screening Visit.
• Ongoing or prior participation in an investigational drug study or use of commercially available CFTR modulator (except physician-prescribed Kalydeco for approved indications) within 30 days of screening.
• Use of restricted medication or food within a specified duration before the Screening Visit or first dose of study drug and/or unwillingness to maintain the restrictions.
• History or evidence of cataract, lens opacity, Y-suture, or lamellar rings determined to be clinically significant by the ophthalmologist during the ophthalmologic examination at the Screening Visit.
• Pregnant and nursing females.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 11 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Birmingham, Alabama, United States

Anchorage, Alaska, United States

Little Rock, Arkansas, United States

Los Angeles, California, United States

Palo Alto, California, United States

Aurora, Colorado, United States

Wilmington, Delaware, United States

Orlando, Florida, United States

St. Petersburg, Florida, United States

Atlanta, Georgia, United States

Boise, Idaho, United States

Indianapolis, Indiana, United States

Boston, Massachusetts, United States

Minneapolis, Minnesota, United States

Kansas City, Missouri, United States

Manchester, New Hampshire, United States

Buffalo, New York, United States

New York, New York, United States

Syracuse, New York, United States

Winston-Salem, North Carolina, United States

Cleveland, Ohio, United States

Pittsburgh, Pennsylvania, United States

Charleston, South Carolina, United States

Sioux Falls, South Dakota, United States

Austin, Texas, United States

Fort Worth, Texas, United States

Houston, Texas, United States

Norfolk, Virginia, United States

Seattle, Washington, United States

Milwaukee, Wisconsin, United States

Vancouver, British Columbia, Canada

Toronto, Ontario, Canada

Montreal, Quebec, Canada

Countries

United States; Canada

References

Walker S, Flume P, McNamara J, Solomon M, Chilvers M, Chmiel J, Harris RS, Haseltine E, Stiles D, Li C, Ahluwalia N, Zhou H, Owen CA, Sawicki G; VX15-661-113 Investigator Group. A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis. J Cyst Fibros. 2019 Sep;18(5):708-713. doi: 10.1016/j.jcf.2019.06.009. Epub 2019 Jun 26.

Reference Type: DERIVED

PMID: 31253540 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001164-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX15-661-113

Identifier Type: -

Identifier Source: org_study_id