Dose Ranging Pharmacokinetics and Pharmacodynamics Study With Mepolizumab in Asthma Patients With Elevated Eosinophils

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01366521
• Date of registration: 12/05/2011
• Prospective Registration: No
• Primary sponsor: GlaxoSmithKline
• Public title: Dose Ranging Pharmacokinetics and Pharmacodynamics Study With Mepolizumab in Asthma Patients With Elevated Eosinophils
• Scientific 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
• Date of first enrolment: February 2011
• Target sample size: 70
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01366521
• Study type: Interventional
• Phase: Phase 2

Countries of recruitment

Estonia, France, Germany, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- 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.

- 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Asthma

Intervention(s)

Biological: Mepolizumab

Primary Outcome(s)

Maximum Change From Baseline in Blood Eosinophils (Emax) [Time Frame: 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 [Time Frame: 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]

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]

Change From Baseline in Blood Eosinophil Levels at Week 12 (Day 84) [Time Frame: Baseline (Day 1 pre-dose) and Week 12]

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]

Time to Maximum Change in Blood Eosinophils Levels (Tmaxeos) [Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140]

Area Under the Blood Eosinophil Time Curve (AUEC) up to Day 84 [Time Frame: Days 1, 3, 7, 28, 56, 70 and 84]

Number of Participants Who Achieved >=50% Eosinophil Repletion by Day 140 [Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140]

Secondary Outcome(s)

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 the Indicated Electrocardiogram (ECG) Findings at Screening and Day 3 [Time Frame: Screening (SCR) and at Day 3]

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]

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]

Mean AUC to Assess the Absolute Bioavailability of SC Mepolizumab [Time Frame: Days 1, 3, 7, 28, 56, 70, 84, 112 and 140]

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)]

Secondary ID(s)

114092

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 10/12/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01366521