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Cystic FibrosisPhase 3NCT02797132

Safety and Pharmacokinetic Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

A Phase 3 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 2 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

This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. 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?
LUM/IVA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
20 sitesin 2 countries
Study dates
May 2016to Sep 2017
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

  • Subjects who weigh ≥8 kilogram (kg) without shoes and wearing light clothing at the Screening Visit
  • Subjects with confirmed diagnosis of CF at the Screening Visit
  • Subjects who are homozygous for the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) mutation

Who cannot join

  • 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 (including antibiotics) for pulmonary disease within 28 days before Day 1
  • A standard 12-lead ECG demonstrating QTc >450 millisecond (msec) at the Screening Visit.
  • History of solid organ or hematological transplantation.
  • Ongoing or prior participation in an investigational drug study (including studies investigating LUM and/or IVA) within 30 days of the Screening Visit.
  • History of cataract/lens opacity or evidence of cataract/lens opacity determined to be clinically significant by a licensed ophthalmologist during the ophthalmologic examination at the Screening Visit

Trial locations and contacts

20 sites in 2 countries.

20 sites in 2 countries

United States17 sites

  • Study site

    Aurora, Colorado

  • Study site

    Boston, Massachusetts

  • Study site

    Buffalo, New York

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Charleston, South Carolina

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Cleveland, Ohio

  • Study site

    Columbus, Ohio

  • Study site

    Houston, Texas

  • Study site

    Indianapolis, Indiana

  • Study site

    Kansas City, Missouri

  • Study site

    Minneapolis, Minnesota

  • Study site

    Norfolk, Virginia

  • Study site

    Palo Alto, California

  • Study site

    Philadelphia, Pennsylvania

  • Study site

    Seattle, Washington

Other trials in United States

Canada3 sites

  • Study site

    Montreal

  • Study site

    Toronto, Ontario

  • Study site

    Vancouver, British Columbia

Other trials in Canada

About this study

Official title: A Phase 3, 2-Part, Open-label Study to Evaluate the Safety and Pharmacokinetics of Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

This is a Phase 3, 2-part (Part A and Part B), open-label, multicenter study evaluating the pharmacokinetics (PK), safety, tolerability, and pharmacodynamics (PD) of multiple doses of lumacaftor/ivacaftor (LUM/IVA) in subjects 2 through 5 years of age (inclusive) with cystic fibrosis (CF), homozygous for F508del. Subjects who participate in Part A may participate in Part B, if they meet the eligibility criteria.

Conditions
Cystic Fibrosis
Being tested
LUM/IVA
Keywords
CF
Medical subject headings
Cystic Fibrosis

What participants receive

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

  • LUM/IVADrug

    Also called Orkambi, VX-809+VX-770

Study groups in NCT02797132
Study groupRoleWhat they receive
Lumacaftor/Ivacaftor (LUM/IVA)ExperimentalPart A (<14 kg): Participants weighing less than (<) 14 kilograms (kg) at screening received LUM 100 milligram (mg)/IVA 125 mg fixed-dose combination every 12 hours for 15 days in Part A. Part A (>=14 kg): Participants weighing greater than or equal to (>=) 14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 15 days in Part A. Part B (<14 kg): Participants weighing <14 kg at screening received LUM 100 mg/IVA 125 mg fixed-dose combination every 12 hours for 24 weeks in Part B. Part B (>=14 kg): Participants weighing >=14 kg at screening received LUM 150 mg/IVA 188 mg fixed-dose combination every 12 hours for 24 weeks in Part B.
Receives: Drug: LUM/IVA

What is being measured

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

  1. Part A: Pre-dose Concentration (Ctrough) of LUM and IVA

    Measured: Day 15

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

    Measured: Day 1 up to Week 26

Secondary outcomes (21)

  1. Part A: Pre-dose Concentration (Ctrough) of LUM and IVA Metabolites

    Measured: Day 15

  2. Part A: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Day 1 up to Day 25

  3. Part B: Absolute Change From Baseline in Sweat Chloride at Week 24

    Sweat samples were collected using an approved collection device.

    Measured: Baseline, Week 24

  4. Part B: Absolute Change From Baseline in Body Mass Index (BMI) at Week 24

    BMI was defined as weight in kilograms (kg) divided by height in square meter (m^2).

    Measured: Baseline, Week 24

  5. Part B: Absolute Change From Baseline in Body Mass Index (BMI) For-Age Z-Score at Week 24

    BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score (BMI z-score).

    Measured: Baseline, Week 24

  6. Part B: Absolute Change From Baseline in Weight at Week 24

    Measured: Baseline, Week 24

  7. Part B: Absolute Change From Baseline in Weight-for-age Z-Score at Week 24

    z-score is a statistical measure to describe whether a mean was above or below the standard. Weight, adjusted for age and sex, was analyzed as weight-for-age z-score (Weight z-score).

    Measured: Baseline, Week 24

  8. Part B: Absolute Change From Baseline in Stature (Height) at Week 24

    Measured: Baseline, Week 24

  9. Part B: Absolute Change From Baseline in Stature-for-Age Z-Score

    z-score is a statistical measure to describe whether a mean was above or below the standard. Stature (height), adjusted for age and sex, was analyzed as Stature-for-age z-score (Stature z-score).

    Measured: Baseline, Week 24

  10. Part B: Number of Pulmonary Exacerbations

    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria.

    Measured: Through Week 24

  11. Part B: Number of Participants With at Least One Pulmonary Exacerbation Pulmonary Exacerbation Through Week 24

    Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol defined criteria. Time to event data was not collected and instead, number of participants with first event were collected and are reported. Time-to-first pulmonary exacerbation was planned to be estimated using Kaplan-Meier (KM) estimates. However, due to less than 50% of events, time-to-first event data was not estimated. Instead, number of participants with at least one pulmonary exacerbation event were collected and are reported.

    Measured: Through Week 24

  12. Part B: Number of Cystic Fibrosis (CF)-Related Hospitalizations

    Measured: Through Week 24

  13. Part B: Absolute Change From Baseline in Fecal Elastase-1 (FE-1) Levels at Week 24

    Measured: Baseline, Week 24

  14. Part B: Absolute Change From Baseline in Serum Levels of Immunoreactive Trypsinogen (IRT) Through Week 24

    Measured: Baseline, Through Week 24

  15. Part B: Number of Participants With Microbiology Culture Status (Positive or Negative) at Week 24

    Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.

    Measured: Baseline and Week 24

  16. Part B: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Week 24

    FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

    Measured: Baseline, Week 24

  17. Part B: Absolute Change in Sweat Chloride From Week 24 at Week 26

    Sweat samples were collected using an approved collection device.

    Measured: Week 24, Week 26

  18. Part B: Acceptability/Palatability of LUM/IVA Granules Measured Using Hedonic Scale

    The acceptability and palatability of LUM/IVA granules was assessed by a visual analog scale that incorporates a 5 point facial hedonic scale (Liked it Very Much, Liked it a Little, Not sure, Disliked it a Little, Disliked it Very Much). The assessment was conducted in 2 steps: assessment of approved food/liquid (Evaluation 1), and assessment of approved food/liquid with LUM/IVA granules (Evaluation 2).

    Measured: Day 1

  19. Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 2.5 at Week 24

    Lung clearance index (LCI) is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.

    Measured: Baseline, Week 24

  20. Part B: Absolute Change From Baseline in Lung Clearance Index (LCI) 5.0 at Week 24

    LCI is a measure of ventilation inhomogeneity that is derived from a multiple breath washout test using Nitrogen (N2). LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.

    Measured: Baseline, Week 24

  21. Part B: Pre-dose Concentration (Ctrough) of LUM and IVA and Its Metabolites

    Measured: Week 24

Timeline

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

  1. First posted13 Jun 2016 (estimated)
  2. Study startMay 2016
  3. Primary completionSep 2017
  4. Study completionSep 2017

Resources

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
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02797132
Sponsor's protocol ID
VX15-809-115
Other IDs
2016-001004-33, 2016
Status last verified
Sep 2018
First submitted
25 May 2016
Last updated
30 Oct 2018
Data monitoring committee
Yes

Publications

  • McNamara JJ, McColley SA, Marigowda G, Liu F, Tian S, Owen CA, Stiles D, Li C, Waltz D, Wang LT, Sawicki GS. Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2-5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study. Lancet Respir Med. 2019 Apr;7(4):325-335. doi: 10.1016/S2213-2600(18)30460-0. Epub 2019 Jan 24.

    PubMed 30686767

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 2 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 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 30 Oct 2018. 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, 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 30 Oct 2018). 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: Pre-dose Concentration (Ctrough) of LUM and IVA (time frame: Day 15). The study lists 2 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 NCT02797132, 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 30 Oct 2018.

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