Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A single blind, placebo controlled, parallel group, single ascending intravenous dose study to assess safety, tolerability, pharmacokinetics and pharmacodynamics of SB-240563 (mepolizumab) in healthy Japanese male subjects.
Trial description: SB-240563 is a fully humanized monoclonal antibody which is specific for human interleukin-5 (IL-5) and has been under development for severe refractory asthma. This study is the first study in Japanese subjects. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single dose SB-240563 administered intravenously to Japanese healthy male subjects.
Primary purpose:
Other
Trial design:
Parallel Assignment
Masking:
Single (Participant)
Allocation:
Randomized
Primary outcomes:
pharmacokinetics
Timeframe: From Day 1 to Follow-Up(Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Safety
Timeframe: From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Secondary outcomes:
blood eosinophil counts
Timeframe: From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
free and total IL5 levels
Timeframe: From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
immunogenicity
Timeframe: From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Interventions:
Biological/vaccine: SB-240563
Other: Placebo
Enrollment:
35
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Clutterbuck EJ; Hirst EM; Sanderson CJ. Human interleukin-5 (IL-5) regulates the production of eosinophils in human bone marrow cultures: comparison and interaction with IL-1, IL-3, IL-6, and GMCSF. Blood 1989;73:1504-1512.
Haldar ; Brightling CE; Hargadon B; Gupta S; Monteiro W; Sousa A; Marshall RP; Bradding P; Green RH; Wardlaw AJ; Pavord ID. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-984.
Hamid Q; Azzawi M; Ying S; Moqbel R; Wardlaw AJ; Corrigan CJ; Bradley B; Durham SR; Collins JV; Jeffery PK et al. Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma. J Clin Invest 1991;87:1541-1546.
Humbert M, Corrigan CJ, Kimmitt P, Till SJ, Kay AB, Durham SR. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 1997;156:704-708.
Robinson DS; Ying S; Bentley AM; Meng Q; North J; Durham SR; Kay AB; Hamid Q. Relationships among numbers of bronchoalveolar lavage cells expressing messenger ribonucleic acid for cytokines, asthma symptoms, and airway methacholine responsiveness in atopic asthma. J Allergy Clin Immunol 1993;92:397-403.
Smith DA; Minthorn EA; Beerahee M. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody. Clin Pharmacol 2011, 50: 215-227
Wang JM; Rambaldi A; Biondi A; Chen ZG; Sanderson CJ; Mantovani A. Recombinant human interleukin 5 is a selective eosinophil chemoattractant. Eur J Immunol 1989;19:701-705.
Wardlaw AJ; Brightling C; Green R; Woltmann G; Pavord I. Eosinophils in asthma and other allergic diseases. Br Med Bull 2000;56:985-1003.
Tsukamoto N, Takahashi N, Itoh H, Pouliquen I.Pharmacokinetics and Pharmacodynamics of Mepolizumab, an Anti–Interleukin 5 Monoclonal Antibody, in Healthy Japanese Male Subjects.Clin Pharmacol Drug Devel.2016;5(2):105-108
Medical condition
Asthma
Product
mepolizumab
Collaborators
Not applicable
Study date(s)
August 2011 to April 2012
Type
Interventional
Phase
1
Participation criteria
Sex
Male
Age
20 - 55 years
Accepts healthy volunteers
Yes
- Healthy Japanese as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
- Japanese defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Japanese subjects should also have lived outside Japan for less than 10 years.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Inclusion and exclusion criteria
Inclusion criteria:
- Healthy Japanese as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
- Japanese defined as being born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Japanese subjects should also have lived outside Japan for less than 10 years.
- Male between 20 and 55 years of age inclusive, at the time of signing the informed consent.
- Body weight equal or more than 45.0 kg and BMI within the range between 18.5 and 29.0 kg/m2 (inclusive).
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- At screening, QTCF<450 msec; or QTcF < 480 msec in subjects with Bundle Branch Block.
- AST, ALT, alkaline phosphatase and bilirubin equal or less than 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Exclusion criteria:
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- A positive pre-study drug/alcohol screen.
- A positive test for HIV antibody.
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units. One unit is equivalent to a 285 mL glass or full strength beer or 425 mL schooner or light beer or 1 (30 mL) measure of spirits or 1 glass (100 mL) of wine (NHMRC Guidelines [NHMRC, 2001])
- 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, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John’s Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 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.
- History of sensitivity to any of 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.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- Unwillingness or inability to follow the procedures outlined in the protocol.
- Subject is mentally or legally incapacitated.
- Subjects with a smoking history of >10 cigarettes per day in the last 3 months.
- The subject’s systolic blood pressure is outside the range of 90-140 mmHg, or diastolic blood pressure is outside the range of 45-90 mmHg or systolic blood pressure drop from supine to standing of >30 mmHg, or heart rate is outside the range of 40-100 bpm for subjects at Screening and pre-dose on Day 1.
- Exposure to live vaccine within the four weeks prior to screening or with intention to receive live vaccine during the study
Trial location(s)
Location
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Status
Terminated/Withdrawn
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2012-27-04
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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