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

NCT02953314 | Completed Phase 3 Results DMC

• 2 other identifiers: VX15-661-1132017-001164-38
• Study Type: interventional
• Target: 83
• Locations: 2 countries
• Sites: 33

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

Outcome Measures

Primary Outcomes (3)

• Part A: Maximum Observed Concentration (Cmax) of TEZ and IVA

  Day 1 and Day 14

• Part A: Area Under the Concentration Versus Time Curve During Dosing Interval (AUCtau) of TEZ and IVA

  Day 1 and Day 14

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

  Day 1 up to Week 28

Secondary Outcomes (16)

• Part A: Cmax of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

  Day 1 and Day 14

• Part A: AUCtau of TEZ Metabolites (M1-TEZ, M2-TEZ) and IVA Metabolites (M1-IVA, M6-IVA)

  Day 1 and Day 14

• Part A: Number of Participants With AEs and SAEs

  Day 1 up to Day 28

• Part B: Cmax of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA)

  Week 16

• Part B: AUCtau of TEZ, TEZ Metabolites (M1-TEZ, M2-TEZ), IVA, and IVA Metabolites (M1-IVA, M6-IVA )

  Week 16

Study Arms (2)

Part A

EXPERIMENTAL

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.

Drug: TEZ; Drug: IVA

Part B

EXPERIMENTAL

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.

Drug: TEZ/IVA; Drug: IVA

Interventions

TEZ DRUG

Also known as: tezacaftor, VX-661

Part A

TEZ/IVA DRUG

Also known as: tezacaftor/ivacaftor, VX-661/VX-770

Part B

IVA DRUG

Also known as: ivacaftor, VX-770

Part A; Part B

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vertex Pharmaceuticals Incorporated: lead

Study Sites (33)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Anchorage, Alaska, United States

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Little Rock, Arkansas, United States

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Los Angeles, California, United States

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Palo Alto, California, United States

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Aurora, Colorado, United States

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Wilmington, Delaware, United States

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Orlando, Florida, United States

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St. Petersburg, Florida, United States

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Atlanta, Georgia, United States

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Boise, Idaho, United States

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Indianapolis, Indiana, United States

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Boston, Massachusetts, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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Manchester, New Hampshire, United States

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Buffalo, New York, United States

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New York, New York, United States

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Syracuse, New York, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Sioux Falls, South Dakota, United States

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Austin, Texas, United States

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Fort Worth, Texas, United States

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Houston, Texas, United States

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Norfolk, Virginia, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Unknown Facility

Montreal, Quebec, Canada

Location

Related Publications (1)

• 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.

  PMID: 31253540 DERIVED

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

tezacaftor; tezacaftor, ivacaftor drug combination; 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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: November 2, 2016
• Study Start: November 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: March 4, 2020
• Results First Posted: December 5, 2019

Record last verified: 2020-02

Locations

US (30); CA (3)