Cystic FibrosisPhase 3NCT02725567
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
A Phase 3 study testing IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 23 sites in 5 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 1 month to 24 months
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 23 sitesin 5 countries
- Study dates
- 2 Jun 2016to 28 Jun 2022
- 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 1 month to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
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
- 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
Show all 10Show fewer
- 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
- Other protocol defined Inclusion/Exclusion Criteria may apply.
Trial locations and contacts
23 sites in 5 countries.
23 sites in 5 countries
United States13 sites
Study site
Atlanta, Georgia
Study site
Baltimore, Maryland
Study site
Birmingham, Alabama
Study site
Boston, Massachusetts
Study site
Chicago, Illinois
Study site
Columbus, Ohio
Study site
Houston, Texas
Study site
Indianapolis, Indiana
Study site
Kansas City, Missouri
Study site
Madison, Wisconsin
Study site
Palo Alto, California
Study site
Philadelphia, Pennsylvania
Study site
Seattle, Washington
United Kingdom5 sites
Study site
Edinburgh
Study site
Leicester
Study site
London
Study site
Manchester
Study site
Oxford
Australia3 sites
Study site
Parkville, Victoria
Study site
South Brisbane
Study site
Westmead
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 Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation
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.
- Conditions
- Cystic Fibrosis
- Being tested
- IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IVADrug
Also called VX-770, ivacaftor
Granules in sachet for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Part A: 3 to <24 months | Experimental | 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. Receives: Drug: IVA |
| Part B + A/B:1 to < 24 months | Experimental | 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. Receives: Drug: IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Measured: Day 1 through Day 70
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Measured: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Measured: Day 1 through Week 38
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Measured: Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
Secondary outcomes (2)
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Measured: Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
Sweat samples were collected using an approved collection device.
Measured: From Baseline at Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2016 (estimated)
- Study start2 Jun 2016
- Primary completion28 Jun 2022
- Study completion28 Jun 2022
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 (2)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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02725567
- Sponsor's protocol ID
- VX15-770-124
- Other IDs
- 2015-001997-16, 2015
- Status last verified
- Aug 2023
- First submitted
- 14 Mar 2016
- Last updated
- 7 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 33023304Rosenfeld 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.
PubMed 29886024
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2023. 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 Less Than 24 Months of Age and Have an Ivacaftor-Responsive CFTR Mutation
- ClinicalTrials.gov ID
- NCT02725567
- Acronym / sponsor ID
- VX15-770-124
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 2 Jun 2016 (actual)
- Primary completion
- 28 Jun 2022 (actual)
- Study completion
- 28 Jun 2022 (actual)
- First posted
- 1 Apr 2016 (estimated)
- Results
- Posted 7 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: 3 to <24 months | Experimental | Drug: IVAParticipants 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. |
| Part B + A/B:1 to < 24 months | Experimental | Drug: IVAParticipants 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. |
Who may qualify
- Ages
- 1 month to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (10 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
- 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
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 |
|---|---|---|
| IVAAlso: VX-770, ivacaftorGranules in sachet for oral administration. | Drug | Part A: 3 to <24 months, Part B + A/B:1 to < 24 months |
Primary outcome
Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time frame: Day 1 through Day 70
Part A: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Pre-dose, 2-4 hours, 6-8 hours, 24-60 hours post-dose
Part B +A/B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs)
Time frame: Day 1 through Week 38
Part A/B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Day 4 (pre-dose, 2-4 hours, 6-8 hours post-dose); Day 15 (pre-dose); Week 4 (pre-dose); Week 8 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 12 (pre-dose); Week 18 (pre-dose) and Week 24 (pre-dose)
2 secondary outcomes
Part B: Observed Plasma Concentration of IVA and Their Metabolites (M1-IVA and M6-IVA)
Time frame: Week 2 (pre-dose, 2-4 hours, 6-8 hours post-dose); Week 8 (pre-dose,1 hour, 4-hour post-dose); Week 24 (pre-dose, 2-4 hours post dose)
Part B + A/B: Absolute Change From Baseline in Sweat Chloride
Time frame: From Baseline at Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33023304Davies 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.
- Derived from this study: PubMed 29886024Rosenfeld 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.
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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.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 23 sites in 5 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 3 inclusion and 10 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 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, United Kingdom, Australia, Canada, Ireland. 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 7 Sep 2023). 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: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious (TEAEs) (time frame: Day 1 through Day 70). The study lists 4 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 NCT02725567, which also lists 2 linked publications.
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 7 Sep 2023.