A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation

NCT ID: NCT02725567

Last Updated: 2023-09-07

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-02

Study Completion Date

2022-06-28

Brief Summary

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The purpose of this study was to evaluate the safety of ivacaftor treatment, and PK of ivacaftor and metabolites in participants with cystic fibrosis (CF) who are \<24 months of age at treatment initiation and have an ivacaftor-responsive CF transmembrane conductance regulator (CFTR) gene mutation.

Detailed Description

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Conditions

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Cystic Fibrosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A: 3 to <24 months

Participants weighing 5 to less than (\<) 7 kilogram (kg) received 25 milligram (mg) IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA administered every 12 hours (q12h) on Days 1 through 3 and 1 morning dose on Day 4.

Group Type EXPERIMENTAL

IVA

Intervention Type DRUG

Granules in sachet for oral administration.

Part B + A/B:1 to < 24 months

Participants 4 to \<6 months of age and weighing greater than or equal to (≥) 5 kg received 25 mg IVA q12h. At 6 months of age and older, participants weighing 5 to \<7 kg received 25 mg IVA, 7 to \<14 kg received 50 mg IVA, and those weighing 14 to \<25 kg received 75 mg IVA q12h for 24 weeks on Part B. For Part A/B, participants 1 to \<4 months weighing 3 kg to \<5 kg received an initial low dose of 5.7 mg q12h IVA and those weighing ≥5 kg received 11.4 mg q12h IVA for the first 15 days of IVA treatment. Doses were maintained or adjusted upward at Day 15 and based on weight and/or age once they reached 4 months of age.

Group Type EXPERIMENTAL

IVA

Intervention Type DRUG

Granules in sachet for oral administration.

Interventions

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IVA

Granules in sachet for oral administration.

Intervention Type DRUG

Other Intervention Names

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VX-770 ivacaftor

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of CF by sweat chloride value or CF mutation criteria.
* Have 1 of the following 10 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H (eligible in regions where ivacaftor is approved for use). Part A/B group may also have other ivacaftor-responsive mutations.
* Hematology, serum chemistry, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator.

Exclusion Criteria

* History of any illness or condition 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 participant
* Colonization with organisms associated with a more rapid decline in pulmonary status at screening (Only for Parts A and B)
* History of abnormal liver function or abnormal liver function at screening
* History of solid organ or hematological transplantation
* Use of any moderate or strong inducers or inhibitors of cytochrome P450 (CYP) 3A within 2 weeks before Day 1
* Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives before screening
* Hemoglobin (Hgb) \<9.5 g/dL at screening
* Chronic kidney disease of Stage 3 or above
* Presence of a non-congenital or progressive lens opacity or cataract at Screening
Minimum Eligible Age

1 Month

Maximum Eligible Age

24 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Birmingham, Alabama, United States

Site Status

Palo Alto, California, United States

Site Status

Atlanta, Georgia, United States

Site Status

Chicago, Illinois, United States

Site Status

Indianapolis, Indiana, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Kansas City, Missouri, United States

Site Status

Columbus, Ohio, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Houston, Texas, United States

Site Status

Seattle, Washington, United States

Site Status

Madison, Wisconsin, United States

Site Status

Parkville, Victoria, Australia

Site Status

South Brisbane, , Australia

Site Status

Westmead, , Australia

Site Status

Toronto, , Canada

Site Status

Dublin, , Ireland

Site Status

Edinburgh, , United Kingdom

Site Status

Leicester, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Oxford, , United Kingdom

Site Status

Countries

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United States Australia Canada Ireland United Kingdom

References

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Davies JC, Wainwright CE, Sawicki GS, Higgins MN, Campbell D, Harris C, Panorchan P, Haseltine E, Tian S, Rosenfeld M. Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial. Am J Respir Crit Care Med. 2021 Mar 1;203(5):585-593. doi: 10.1164/rccm.202008-3177OC.

Reference Type DERIVED
PMID: 33023304 (View on PubMed)

Rosenfeld M, Wainwright CE, Higgins M, Wang LT, McKee C, Campbell D, Tian S, Schneider J, Cunningham S, Davies JC; ARRIVAL study group. Ivacaftor treatment of cystic fibrosis in children aged 12 to <24 months and with a CFTR gating mutation (ARRIVAL): a phase 3 single-arm study. Lancet Respir Med. 2018 Jul;6(7):545-553. doi: 10.1016/S2213-2600(18)30202-9. Epub 2018 Jun 7.

Reference Type DERIVED
PMID: 29886024 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2015-001997-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VX15-770-124

Identifier Type: -

Identifier Source: org_study_id

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