AsthmaPhase 2NCT01366521
Dose Ranging Pharmacokinetics and Pharmacodynamics Study With Mepolizumab in Asthma Patients With Elevated Eosinophils
A Phase 2 study testing Mepolizumab in people with Asthma, run by GlaxoSmithKline at 11 sites in 4 countries.
Trial summary
A multi-center, randomized, open-label, parallel-group, repeat dose study in asthma patients with elevated eosinophils. Eligible subjects will receive 3 doses (28 days apart) of mepolizumab given intravenous (IV) or subcutaneously (SC). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- Mepolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 11 sitesin 4 countries
- Study dates
- Feb 2011to Mar 2012
- Phase
- Phase 2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or eligible females between 18 and 65 years of age inclusive, at the time of signing the informed consent; Non-childbearing potential is defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. To be eligible for entry into the study, females of child-bearing potential and females whose menopausal status is in question must commit to consistent and correct use of an acceptable method of birth control as defined in Section 7.1.1 from one month prior to the first dose of investigational product until 4 months after the last dose of investigational product.
- History of asthma for at least one year.
- Subjects must be on a stable dose of an inhaled corticosteroid or combination (ICS+LABA) therapy for at least 12 weeks prior to screening.
- FEV1≥45% and <90 % of predicted normal value during screening (obtained between 6:00 AM and 1:00 PM).
- Evidence of airway reversibility (FEV1≥12%) within 30 minutes of inhalation of albuterol OR airway hyperresponsiveness (PC20 of <8mg/mL or PD20 of <7.8 µ mol methacholine/histamine) documented in the 12 months prior to randomization.
- Subjects with documented evidence of elevated blood eosinophilia levels (>0.3 cells 109/L) within 12 months of screening and evidence of elevated blood eosinophilia levels (>0.3 cells 109/L) at screening.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Who cannot join
- QTcF ≥450 msec; or QTcF ≥ 480 msec in subjects with Bundle Branch Block.
- AST, ALT, alkaline phosphatase and bilirubin ≥ 1.5xULN (isolated bilirubin <1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin ≥35%).
- Subjects with elevated blood eosinophil levels which is not related to asthma
- Current smokers (any subject who has smoked within the six months prior to screening or has a positive urine cotinine at screening) or subjects with a smoking history of >10 pack years calculated as follows:
- Number of cigarettes per day X number of years smoked 20
- Presence of a clinically important lung condition other than asthma including current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, Churg-Strauss syndrome, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
Show all 22Show fewer
- An asthma exacerbation or respiratory tract infection within six weeks prior to screening (an exacerbation is defined as worsening asthma requiring the use of systemic corticosteroids and/or emergency department visit, hospitalisation).
- Subjects with a parasitic infestation within six months of screening.
- A current malignancy or previous history of cancer in remission for less than five years prior screening (except for localized carcinoma of the skin that has been resected for cure).
- Subjects who have clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Subjects with a known immunodeficiency (e.g. human immunodeficiency virus - HIV).
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within three months of screening.
- Subjects who have received omalizumab [Xolair] within 130 days of administration of the first dose of study medication.
- Subjects with recent history (within two years prior to screening) of alcohol misuse or substance abuse prior screening.
- A positive pre-study drug/alcohol test at screening.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, five half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Subjects who have previously participated in a study of mepolizumab and received study medication within 90 days prior to screening.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements within seven days (or 14 days if the drug is a potential enzyme inducer) or five half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Exposure to live vaccine within the four weeks prior to screening and no intention to receive live vaccine during the study.
- History of sensitivity to the study medications (or components thereof) or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- Pregnant or lactating females; pregnancy as determined by positive pregnancy test at screening or prior to dosing.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
Germany4 sites
GSK Investigational Site
Berlin, State of Berlin, 14050
GSK Investigational Site
Frankfurt am Main, Hesse, 60596
GSK Investigational Site
Gauting, Bavaria, 82131
GSK Investigational Site
Magdeburg, Saxony-Anhalt, 39112
France3 sites
GSK Investigational Site
Marseille, 13915
GSK Investigational Site
Montpellier, 34295
GSK Investigational Site
Pessac, 33604
United States2 sites
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Winston-Salem, North Carolina, 27103
Estonia2 sites
GSK Investigational Site
Tallinn, 13619
GSK Investigational Site
Tartu, 51014
About this study
Official title: A Multicenter, Open-label, Dose Ranging Study to Determine the Pharmacokinetics and Pharmacodynamics of Mepolizumab Administered Intravenously or Subcutaneously to Adult Asthmatic Subjects With Elevated Blood Eosinophil Levels
A multi-center, randomized, open-label, parallel-group, repeat dose study in asthma patients with elevated eosinophils. Eligible subjects will receive 3 doses (28 days apart) of mepolizumab given intravenous (IV) or subcutaneously (SC). Blood samples for safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity analysis, as well as safety/tolerability assessments will be collected throughout the study
Read the detailed description
Mepolizumab (SB-240563) is a humanized monoclonal antibody that blocks human interleukin 5 (IL-5) from binding to its receptor. Mepolizumab is currently under development for severe refractory asthma and a Phase IIB dose-ranging study using the IV route of administration is currently on-going. This study will be a multi-center, randomized, open-label, parallel-group, repeat dose study conducted in approximately 65 subjects with established asthma and elevated blood eosinophil levels. Dosing will occur on three occasions, every four weeks [Day 1, Day 28 (+/- 3 days) and Day 56 (+/- 3 days)]. Blood samples for safety, pharmacodynamics (PD), pharmacokinetics (PK) and immunogenicity analysis, as well safety and tolerability assessments will be collected/assessed throughout the study. Each subject will participate in the study for up to approximately 22 weeks, including screening, dosing and follow-up.
- Conditions
- Asthma
- Being tested
- Mepolizumab
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabBiological
Monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| Mepolizumab 250 mg subcutaneous (SC) | Experimental | 250 mg subcutaneous (SC) Receives: Biological: Mepolizumab |
| Mepolizumab 125 mg subcutaneous (SC) | Experimental | 125 mg subcutaneous (SC) Receives: Biological: Mepolizumab |
| Mepolizumab 12.5 mg subcutaneous (SC) | Experimental | 12.5 mg subcutaneous (SC) Receives: Biological: Mepolizumab |
| Mepolizimab 75 mg intravenously (I.V.) | Experimental | 75 mg intravenously (I.V.) Receives: Biological: Mepolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84)
Change from Baseline in blood eosinophils was calculated as the post-Baseline value minus the Baseline value. The change from Baseline in log-transformed blood eosinophil levels at Week 12 was analyzed using both a linear and non-linear (Imax) dose response models. The dose response was found to be non-linear and hence only the results of the non-linear model are presented. Mepolizumab 75mg IV assumed to equate to 100 mg SC within model. Prior to log10-transformation, zero values were imputed with half the minimum value across all dose groups and time points. An adjustment for Baseline eosinophil count was also incorporated into the model.
Measured: Baseline (Day 1 pre-dose) and Week 12
Area Under the Blood Eosinophil Time Curve (AUEC) up to Day 84
Area under the absolute blood eosinophil time curve to Day 84 (AUECeos[0-day 84]) determined using the linear trapezoidal rule for subset of participants with blood eosinophil data to Day 84. Blood samples for the analyses of AUEC(eos) (0-day 84) were collected at Days 1, 3, 7, 28, 56, 70 and 84.
Measured: Days 1, 3, 7, 28, 56, 70 and 84
Maximum Change From Baseline in Blood Eosinophils (Emax)
Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the maximum reduction from Baseline in blood eosinophils between Day 1 pre-dose and last quantifiable study measurement. Change from Baseline was calculated as the ratio of the post-Baseline value divided by the Baseline value. The maximum reduction from Baseline in eosinophils is represented by the minimum ratio to Baseline.
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Time to Maximum Change in Blood Eosinophils Levels (Tmaxeos)
Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the time to first occurrence of maximum reduction from baseline in blood eosinophil levels between Day 1 pre-dose and last quantifiable study measurement.
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Number of Participants Who Achieved >=50% Eosinophil Repletion by Day 140
This summarizes the number of participants who returned to at least 50% of their Baseline blood eosinophil levels after maximum inhibition had been achieved and without any subsequent decrease in blood eosinophil levels. Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140.
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Mean Area Under the Plasma-concentration Time Curve (AUC) Following SC and IV Administration of Mepolizumab
AUC of mepolizumab was estimated by population modeling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Individual cumulative plasma of mepolizumab AUC to Day 84 (cumAUC(0-day 84)), is the sum of the AUCs over each dosing interval after each of the three doses administered, for those participants with data up to Day 84. Individual cumulative plasma of mepolizumab AUC to Day 140 (cumAUC(0-day 140) is the sum of the AUCs over each dosing interval after each of the three doses administered plus the AUC post the last dose interval up to Day 140 (i.e. from Day 84 to Day 140). Blood samples for PK analyses were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 hour (h), 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Maximum Plasma Concentration (Cmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Maximum plasma concentration was estimated by population modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Time to Maximum Plasma Concentration (Tmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Time to maximum plasma concentration was estimated by population modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Terminal Half-life (t½) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Terminal half-life (t1/2) was estimated by modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters for mepolizumab from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Secondary outcomes (8)
Number of Participants With Clinical Chemistry Parameters Outside the Normal Range Following Treatment
Clinical chemistry laboratory parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB) and direct bilirubin, creatinine, chloride, uric acid, glucose, total carbondioxide (CO2), gamma glutamyltransferase (GGT), albumin, sodium, calcium, alkaline phosphatase (ALP) and total protein assessed at Baseline, Weeks 4, 8, 12 and 20. Laboratory abnormalities outside the normal range (high and low values) at any time post-Baseline are presented.
Measured: Baseline (Day 1 pre-dose), Weeks 4, 8, 12 and 20
Number of Participants With Hematology Laboratory Parameters Outside the Normal Range at Following Treatment
Hematology laboratory parameters included platelet count, red blood cells (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, reticulocyte count, mean corpuscle volume (MCV), mean corpuscle hemoglobin (MCH), mean corpuscle hemoglobin concentration (MCHC), neutrophils, segmented neutrophils (SN), total neutrophils (TN), lymphocytes, monocytes, eosinophils and basophils assessed at Baseline, Weeks 4, 8, 12 and 20. Hematology abnormalities outside the normal range (high and low values) at any time post-Baseline are presented.
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 (follow-up visit)
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Vital sign measurements including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at Baseline (pre-dose Day 1), Day 1 (30 minutes, 1 h, 2 h), Day 28 (pre-dose, 30 minutes, 1 h, 2 h), Day 56 (pre-dose, 30 minutes, 1 h, 2 h), Day 84, Day 112 and follow-up (Day 140).
Measured: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Change From Baseline in Heart Rate Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Vital sign measurements including heart rate (HR) was measured at Baseline (Pre-dose Day 1), Day 1 (30 minutes, 1 h, 2 h), Day 28 (pre-dose, 30 minutes, 1 h, 2 h), Day 56 (pre-dose, 30 minutes, 1 h, 2 h), Day 84, Day 112 and follow-up (Day 140).
Measured: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Number of Participants With Levels of Anti-mepolizumab Antibodies at Indicated Time Points
Blood samples were collected for the determination of anti-mepolizumab antibodies by antibody detection (AD) and antibody neutralisation (AN) assay. For participants who prematurely withdrew from the study and had been dosed, immunogenicity testing occurred (if possible) at the time of premature withdrawal and at 16 weeks after dosing (or the end of the study, whichever came first). Serum was tested for the presence of anti-mepolizumab antibodies using the currently approved analytical methodology incorporating screening, confirmation and titration steps. Samples confirmed positive for the presence of anti-mepolizumab antibodies in the original assay were tested for the presence of neutralizing antibodies.
Measured: Day 1, Day 112 and Day 140
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Screening and Day 3
The number of participants with normal, abnormal - clinically significant (CS), and abnormal - not clinically significant (NCS) ECG findings, as well as the number of participants with no results (NR), at Screening (SCR) and Day 3 are presented. Findings were determined to be normal, abnormal CS, and NCS by the investigator.
Measured: Screening (SCR) and at Day 3
Mean AUC to Assess the Absolute Bioavailability of SC Mepolizumab
Population modelling techniques using non-linear mixed effect methods were used to estimate individual and population pharmacokinetic parameters from the sparse sampling. Log-transformed individual clearance estimates were analysed using an analysis of variance (ANOVA) model. The absolute bioavailability for each SC dose group and across SC doses will be estimated from the model together with associated 90% confidence intervals. Blood samples for PK analyses were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Mean Dose Normalized Cmax Ratio to Assess the Relative Bioavailability of SC Mepolizumab as Compared With IV Mepolizumab
Maximum plasma concentration was estimated by population modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Log-transformed dose-normalized (DM) Cmax were be analyzed using an analysis of variance (ANOVA) model. The ratio for each SC dose group versus IV and across SC doses versus IV will be estimated from the model together with associated 90% confidence intervals. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Measured: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2011 (estimated)
- Study startFeb 2011
- Primary completionMar 2012
- Study completionMar 2012
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.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01366521
- Sponsor's protocol ID
- 114092
- Status last verified
- Nov 2016
- First submitted
- 12 May 2011
- Last updated
- 11 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Dose Ranging Study to Determine the Pharmacokinetics and Pharmacodynamics of Mepolizumab Administered Intravenously or Subcutaneously to Adult Asthmatic Subjects With Elevated Blood Eosinophil Levels
- ClinicalTrials.gov ID
- NCT01366521
- Acronym / sponsor ID
- 114092
- Conditions
- Asthma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- Feb 2011
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 6 Jun 2011 (estimated)
- Results
- Posted 10 Dec 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A multi-center, randomized, open-label, parallel-group, repeat dose study in asthma patients with elevated eosinophils. Eligible subjects will receive 3 doses (28 days apart) of mepolizumab given intravenous (IV) or subcutaneously (SC). Blood samples for safety, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity analysis, as well as safety/tolerability assessments will be collected throughout the study
Detailed description
Mepolizumab (SB-240563) is a humanized monoclonal antibody that blocks human interleukin 5 (IL-5) from binding to its receptor. Mepolizumab is currently under development for severe refractory asthma and a Phase IIB dose-ranging study using the IV route of administration is currently on-going. This study will be a multi-center, randomized, open-label, parallel-group, repeat dose study conducted in approximately 65 subjects with established asthma and elevated blood eosinophil levels. Dosing will occur on three occasions, every four weeks [Day 1, Day 28 (+/- 3 days) and Day 56 (+/- 3 days)]. Blood samples for safety, pharmacodynamics (PD), pharmacokinetics (PK) and immunogenicity analysis, as well safety and tolerability assessments will be collected/assessed throughout the study. Each subject will participate in the study for up to approximately 22 weeks, including screening, dosing and follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Mepolizumab 250 mg subcutaneous (SC) | Experimental | Biological: Mepolizumab250 mg subcutaneous (SC) |
| Mepolizumab 125 mg subcutaneous (SC) | Experimental | Biological: Mepolizumab125 mg subcutaneous (SC) |
| Mepolizumab 12.5 mg subcutaneous (SC) | Experimental | Biological: Mepolizumab12.5 mg subcutaneous (SC) |
| Mepolizimab 75 mg intravenously (I.V.) | Experimental | Biological: Mepolizumab75 mg intravenously (I.V.) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males or eligible females between 18 and 65 years of age inclusive, at the time of signing the informed consent; Non-childbearing potential is defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol < 40 pg/ml (<147 pmol/L) is confirmatory]. To be eligible for entry into the study, females of child-bearing potential and females whose menopausal status is in question must commit to consistent and correct use of an acceptable method of birth control as defined in Section 7.1.1 from one month prior to the first dose of investigational product until 4 months after the last dose of investigational product.
- History of asthma for at least one year.
- Subjects must be on a stable dose of an inhaled corticosteroid or combination (ICS+LABA) therapy for at least 12 weeks prior to screening.
- FEV1≥45% and <90 % of predicted normal value during screening (obtained between 6:00 AM and 1:00 PM).
- Evidence of airway reversibility (FEV1≥12%) within 30 minutes of inhalation of albuterol OR airway hyperresponsiveness (PC20 of <8mg/mL or PD20 of <7.8 µ mol methacholine/histamine) documented in the 12 months prior to randomization.
Key exclusion criteria (22 listed)
- QTcF ≥450 msec; or QTcF ≥ 480 msec in subjects with Bundle Branch Block.
- AST, ALT, alkaline phosphatase and bilirubin ≥ 1.5xULN (isolated bilirubin <1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin ≥35%).
- Subjects with elevated blood eosinophil levels which is not related to asthma
- Current smokers (any subject who has smoked within the six months prior to screening or has a positive urine cotinine at screening) or subjects with a smoking history of >10 pack years calculated as follows:
- Number of cigarettes per day X number of years smoked 20
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 |
|---|---|---|
| MepolizumabMonoclonal antibody | Biological | Mepolizimab 75 mg intravenously (I.V.), Mepolizumab 12.5 mg subcutaneous (SC), Mepolizumab 125 mg subcutaneous (SC), Mepolizumab 250 mg subcutaneous (SC) |
Primary outcome
Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84)
Time frame: Baseline (Day 1 pre-dose) and Week 12
Change from Baseline in blood eosinophils was calculated as the post-Baseline value minus the Baseline value. The change from Baseline in log-transformed blood eosinophil levels at Week 12 was analyzed using both a linear and non-linear (Imax) dose response models. The dose response was found to be non-linear and hence only the results of the non-linear model are presented. Mepolizumab 75mg IV assumed to equate to 100 mg SC within model. Prior to log10-transformation, zero values were imputed with half the minimum value across all dose groups and time points. An adjustment for Baseline eosinophil count was also incorporated into the model.
Area Under the Blood Eosinophil Time Curve (AUEC) up to Day 84
Time frame: Days 1, 3, 7, 28, 56, 70 and 84
Area under the absolute blood eosinophil time curve to Day 84 (AUECeos[0-day 84]) determined using the linear trapezoidal rule for subset of participants with blood eosinophil data to Day 84. Blood samples for the analyses of AUEC(eos) (0-day 84) were collected at Days 1, 3, 7, 28, 56, 70 and 84.
Maximum Change From Baseline in Blood Eosinophils (Emax)
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the maximum reduction from Baseline in blood eosinophils between Day 1 pre-dose and last quantifiable study measurement. Change from Baseline was calculated as the ratio of the post-Baseline value divided by the Baseline value. The maximum reduction from Baseline in eosinophils is represented by the minimum ratio to Baseline.
Time to Maximum Change in Blood Eosinophils Levels (Tmaxeos)
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 to assess the time to first occurrence of maximum reduction from baseline in blood eosinophil levels between Day 1 pre-dose and last quantifiable study measurement.
Number of Participants Who Achieved >=50% Eosinophil Repletion by Day 140
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
This summarizes the number of participants who returned to at least 50% of their Baseline blood eosinophil levels after maximum inhibition had been achieved and without any subsequent decrease in blood eosinophil levels. Blood samples were collected at Days 1, 3, 7, 28, 56, 70, 84, 112 and 140.
Mean Area Under the Plasma-concentration Time Curve (AUC) Following SC and IV Administration of Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
AUC of mepolizumab was estimated by population modeling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Individual cumulative plasma of mepolizumab AUC to Day 84 (cumAUC(0-day 84)), is the sum of the AUCs over each dosing interval after each of the three doses administered, for those participants with data up to Day 84. Individual cumulative plasma of mepolizumab AUC to Day 140 (cumAUC(0-day 140) is the sum of the AUCs over each dosing interval after each of the three doses administered plus the AUC post the last dose interval up to Day 140 (i.e. from Day 84 to Day 140). Blood samples for PK analyses were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 hour (h), 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Maximum Plasma Concentration (Cmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Maximum plasma concentration was estimated by population modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Time to Maximum Plasma Concentration (Tmax) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Time to maximum plasma concentration was estimated by population modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
Terminal Half-life (t½) From Pre-dose (Day 1) to Day 140 for Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Terminal half-life (t1/2) was estimated by modelling techniques using non-linear mixed effect methods for the individual and population pharmacokinetic parameters for mepolizumab from the sparse sampling. Blood samples for PK analyses of mepolizumab were collected on dosing days (Days 1, 28 and 56) at pre-dose and 0.5 h, 1 h and 2 h post-dose (time was relative to the end of infusion in the IV cohort) as well as on Days 3, 7, 70, 84, 112 and 140 (follow-up visit).
8 secondary outcomes
Number of Participants With Clinical Chemistry Parameters Outside the Normal Range Following Treatment
Time frame: Baseline (Day 1 pre-dose), Weeks 4, 8, 12 and 20
Number of Participants With Hematology Laboratory Parameters Outside the Normal Range at Following Treatment
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140 (follow-up visit)
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Time frame: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Change From Baseline in Heart Rate Assessed at Baseline, Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Time frame: Baseline (Day 1 pre-dose) and at Day 1, Day 28, Day 56, Day 84, Day 112 and Day 140
Number of Participants With Levels of Anti-mepolizumab Antibodies at Indicated Time Points
Time frame: Day 1, Day 112 and Day 140
Number of Participants With the Indicated Electrocardiogram (ECG) Findings at Screening and Day 3
Time frame: Screening (SCR) and at Day 3
Mean AUC to Assess the Absolute Bioavailability of SC Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Mean Dose Normalized Cmax Ratio to Assess the Relative Bioavailability of SC Mepolizumab as Compared With IV Mepolizumab
Time frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mepolizumab in people with Asthma, run by GlaxoSmithKline at 11 sites in 4 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 7 inclusion and 22 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 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in Germany, France, United States, Estonia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 10 Dec 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?
Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84) (time frame: Baseline (Day 1 pre-dose) and Week 12). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jan 2017.