Cystic FibrosisPhase 3NCT01705145

Study of Ivacaftor in Cystic Fibrosis Subjects 2 Through 5 Years of Age With a CFTR Gating Mutation

A Phase 3 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD), of ivacaftor in children with cystic fibrosis (CF) who are 2 through 5 years of age and have a CF Transmembrane Conductance Regulator (CFTR) gating mutation in at least 1 allele. Read more about this study

Who is it for?: Ages 2 to 5 years
Conditions the study is for: Cystic Fibrosis
What is being tested?: Ivacaftor
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 20 sitesin 3 countries
Study dates: Jan 2013to Mar 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 5 years
All sexes
No healthy volunteers
Child

Who may be able to join

Male or female with confirmed diagnosis of CF
Must have a CFTR gating mutation in at least 1 allele
Aged 2 through 5 years at screening and Day 1
Weight >= 8 kg at screening and Day 1
Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator

Who cannot join

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
An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
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

Trial locations and contacts

20 sites in 3 countries.

Country

City, postcode or hospital

20 sites in 3 countries

United States16 sites

Study site
Atlanta, Georgia
Study site
Aurora, Colorado
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Charlottesville, Virginia
Study site
Detroit, Michigan
Study site
Grand Rapids, Michigan
Study site
Indianapolis, Indiana
Study site
Kansas City, Missouri
Study site
Lexington, Kentucky
Study site
Minneapolis, Minnesota
Study site
Omaha, Nebraska
Study site
Pittsburgh, Pennsylvania
Study site
Richmond, Virginia
Study site
Salt Lake City, Utah
Study site
Seattle, Washington

Other trials in United States

United Kingdom3 sites

Study site
Edinburgh
Study site
Liverpool
Study site
London

Other trials in United Kingdom

Canada1 site

Study site
Vancouver

Other trials in Canada

About this study

Official title: A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation

Part A is designed to evaluate the safety and PK of multiple-dose administration of ivacaftor in participants 2 through 5 years of age and to confirm the doses for Part B. Part B is designed to evaluate the safety, PK, PD, and efficacy of ivacaftor in participants 2 through 5 years of age.

Conditions: Cystic Fibrosis
Being tested: Ivacaftor
Keywords: Cystic Fibrosis
Medical subject headings: Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IvacaftorDrug
Also called Kalydeco, VX-770

Study groups in NCT01705145
Study group	Role	What they receive
Ivacaftor	Experimental	Part A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study. Receives: Drug: Ivacaftor

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Measured: Part A: Up to 93 Days
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event.
Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
Measured: Part B: Up to 28 Weeks
Part A: Plasma Concentration of Ivacaftor and Its Metabolites
Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.
Measured: Part A: up to 24 hours post-dose on Day 4

Secondary outcomes (5)

Part B: Plasma Concentration of Ivacaftor and Its Metabolites
Plasma concentration was reported for ivacaftor and its metabolites (M1 and M6) up to 24 hours post-dose on Day 168 (Hour 0 [predose] on Day 1, 14, 56, 112, and 168; 2, 3, 6 hours post-dose on Day 14; 1 hour post-dose on Day 56; 4, 6 hours post-dose on Day 112; 24 hours post-dose on Day 168). Data was planned to be reported for overall participants in the period.
Measured: Part B: up to 24 hours post-dose on Day 168
Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was reported as per the dose received and for overall participants.
Measured: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Weight at Week 24
Data was reported as per the dose received and for overall participants.
Measured: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Stature at Week 24
Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Data was reported as per the dose received and for overall participants.
Measured: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
BMI = (Weight [in kg]) divided by (Stature [in meters])^2. Data was reported as per the dose received and for overall participants.
Measured: Baseline, Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2013Mar 2014

First posted12 Oct 2012 (estimated)
Study startJan 2013
Primary completionMar 2014
Study completionMar 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cystic FibrosisStudies of the same condition, open and under way.
More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01705145
Sponsor's protocol ID: VX11-770-108
Other IDs: KIWI
Status last verified: Mar 2016
First submitted: 8 Oct 2012
Last updated: 5 Apr 2016
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Davies JC, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Robertson S, Green Y, Cooke J, Rosenfeld M; KIWI Study Group. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016 Feb;4(2):107-15. doi: 10.1016/S2213-2600(15)00545-7. Epub 2016 Jan 21.
PubMed 26803277

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation
ClinicalTrials.gov ID: NCT01705145
Acronym / sponsor ID: VX11-770-108
Conditions: Cystic Fibrosis
Keywords: Cystic Fibrosis
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 35 participants (actual)
Lead sponsor: Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
Collaborators: Cystic Fibrosis Foundation
Study start: Jan 2013
Primary completion: Mar 2014 (actual)
Study completion: Mar 2014 (actual)
First posted: 12 Oct 2012 (estimated)
Results: Posted 24 Apr 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Ivacaftor	Experimental	Drug: IvacaftorPart A: Ivacaftor 50 milligram (mg) (for participants weighing less than [<] 14 kilograms [kg]) or 75 mg (for participants weighing greater than or equal to [>=] 14 kg) every 12 hours (q12h) from Day 1 through Day 3 and 1 morning dose on Day 4 during Part A of the study.. Part B: Ivacaftor 50 mg (for participants weighing <14 kg) or 75 mg (for participants weighing >=14 kg) q12h for 24 weeks during Part B of the study.

Who may qualify

Ages: 2 to 5 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (5 listed)

Male or female with confirmed diagnosis of CF
Must have a CFTR gating mutation in at least 1 allele
Aged 2 through 5 years at screening and Day 1
Weight >= 8 kg at screening and Day 1
Hematology, serum chemistry, coagulation, and vital signs results at screening with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator

Key exclusion criteria (6 listed)

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
An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks before Day 1
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IvacaftorAlso: Kalydeco, VX-770	Drug	Ivacaftor

Primary outcome

Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
Time frame: Part A: Up to 93 Days
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received and for overall participants.
Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs
Time frame: Part B: Up to 28 Weeks
AE: any adverse change from participant's baseline (pre-treatment) condition, including any adverse experience, abnormal recording/clinical laboratory assessment which occurs during course of study, whether it is considered related to study drug or not. AE includes both serious and non-serious AE. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Related AEs includes all AEs for which the causality was either related to study drug or possibly related to study drug. Data was reported as per the dose received.
Part A: Plasma Concentration of Ivacaftor and Its Metabolites
Time frame: Part A: up to 24 hours post-dose on Day 4
Plasma concentration was reported for ivacaftor and its metabolites (hydroxymethyl ivacaftor [M1] and ivacaftor carboxylate [M6]) up to 24 hours post-dose on Day 4 (Hour 0 [pre-dose] on Day 1 and Day 4; 2, 3, 6, 24 hours post-dose on Day 4). Data was planned to be reported for overall participants in the period.

5 secondary outcomes

Part B: Plasma Concentration of Ivacaftor and Its Metabolites
Time frame: Part B: up to 24 hours post-dose on Day 168
Part B: Absolute Change From Baseline in Sweat Chloride at Week 24
Time frame: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Weight at Week 24
Time frame: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Stature at Week 24
Time frame: Part B: Baseline, Week 24
Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24
Time frame: Baseline, Week 24

Results and safety

Results posted to the registry on 24 Apr 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ivacaftor	9	9

Primary outcome: Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

Time frame: Part A: Up to 93 Days. Number. Unit: participants

Measure	Part A: Ivacaftor 50 mg n = 4	Part A: Ivacaftor 75 mg n = 5	Part A: Overall Ivacaftor n = 9
AEs	3	5	8
SAEs	0	0	0
Related AEs	1	3	4

Population analysed: Part A Safety set included all participants who received at least 1 dose of study drug in part A.

Primary outcome: Part B: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs

Time frame: Part B: Up to 28 Weeks. Number. Unit: participants

Measure	Part B: Ivacaftor 50 mg n = 10	Part B: Ivacaftor 75 mg n = 24	Part B: Overall Ivacaftor n = 34
AEs	10	23	33
SAEs	3	3	6
Related AEs	3	8	11

Population analysed: Part B Safety set included all participants who received at least 1 dose of study drug in part B.

Primary outcome: Part A: Plasma Concentration of Ivacaftor and Its Metabolites

Time frame: Part A: up to 24 hours post-dose on Day 4. Mean (Standard Deviation). Unit: nanogram per milliliter (ng/mL)

Measure	Part A: Overall Ivacaftor n = 9
Ivacaftor: Hour 0 on Day 1	0.00 (0.00)
Ivacaftor: Hour 0 on Day 4	396 (337)
Ivacaftor: 2 Hours Post-Dose on Day 4	726 (284)
Ivacaftor: 3 Hours Post-Dose on Day 4	957 (283)
Ivacaftor: 6 Hours Post-Dose on Day 4	542 (241)
Ivacaftor: 24 Hours Post-Dose on Day 4	124 (149)
M1: Hour 0 on Day 1	0.00 (0.00)
M1: Hour 0 on Day 4	1240 (723)

Population analysed: Part A Safety set included all participants who received at least 1 dose of study drug in part A.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Part A: up to 93 days; Part B: up to 28 weeks. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Ivacaftor 50 mg	0 of 4 (0%)	3 of 4 (75%)	Not reported
Part A: Ivacaftor 75 mg	0 of 5 (0%)	5 of 5 (100%)	Not reported
Part A: Overall Ivacaftor	0 of 9 (0%)	8 of 9 (88.9%)	Not reported
Part B: Ivacaftor 50 mg	3 of 10 (30%)	9 of 10 (90%)	Not reported
Part B: Ivacaftor 75 mg	3 of 24 (12.5%)	23 of 24 (95.8%)	Not reported
Part B: Overall Ivacaftor	6 of 34 (17.6%)	32 of 34 (94.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26803277Davies JC, Cunningham S, Harris WT, Lapey A, Regelmann WE, Sawicki GS, Southern KW, Robertson S, Green Y, Cooke J, Rosenfeld M; KIWI Study Group. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016 Feb;4(2):107-15. doi: 10.1016/S2213-2600(15)00545-7. Epub 2016 Jan 21.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Margaret Rosenfeld, MD principal investigator

Seattle Children's Hospital

Jane Davies, MD principal investigator

Imperial College London

20 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Related AEs (time frame: Part A: Up to 93 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01705145, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2016.