Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01471327




Registration number
NCT01471327
Ethics application status
Date submitted
10/11/2011
Date registered
15/11/2011
Date last updated
20/06/2017

Titles & IDs
Public title
Japanese Phase 1 Study of Mepolizumab
Scientific 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.
Secondary ID [1] 0 0
115705
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - SB-240563
Other interventions - Placebo

Experimental: SB-240563, 10mg - IV, single dose at Day 1

Experimental: Placebo - Saline IV, single dose at Day 1

Experimental: SB-240563, 75mg - IV, single dose at Day 1

Experimental: SB-240563, 250mg - IV, single dose at Day 1

Experimental: SB-240563, 750mg - IV, single dose at Day 1


Other interventions: SB-240563
10mg, 75mg, 250mg and 750mg IV, single dose on Day 1

Other interventions: Placebo
Saline IV, single dose at Day 1
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
pharmacokinetics
Timepoint [1] 0 0
From Day 1 to Follow-Up(Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Primary outcome [2] 0 0
Safety
Timepoint [2] 0 0
From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Secondary outcome [1] 0 0
blood eosinophil counts
Timepoint [1] 0 0
From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Secondary outcome [2] 0 0
free and total IL5 levels
Timepoint [2] 0 0
From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)
Secondary outcome [3] 0 0
immunogenicity
Timepoint [3] 0 0
From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)

Eligibility
Key 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%).
Minimum age
20 Years
Maximum age
55 Years
Sex
Males
Can healthy volunteers participate?
Yes
Key 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

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/04/2012
Sample size
Target
Accrual to date
Final
35
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01471327
Trial related presentations / 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 May 1;73(6):1504-12.
Haldar P, 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 Mar 5;360(10):973-84. doi: 10.1056/NEJMoa0808991. Erratum In: N Engl J Med. 2011 Feb 10;364(6):588.
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 May;87(5):1541-6. doi: 10.1172/JCI115166.
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 Sep;156(3 Pt 1):704-8. doi: 10.1164/ajrccm.156.3.9610033.
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 Sep;92(3):397-403. doi: 10.1016/0091-6749(93)90118-y.
Smith DA, Minthorn EA, Beerahee M. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin-5 monoclonal antibody. Clin Pharmacokinet. 2011 Apr;50(4):215-27. doi: 10.2165/11584340-000000000-00000.
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 Apr;19(4):701-5. doi: 10.1002/eji.1830190420.
Wardlaw AJ, Brightling C, Green R, Woltmann G, Pavord I. Eosinophils in asthma and other allergic diseases. Br Med Bull. 2000;56(4):985-1003. doi: 10.1258/0007142001903490.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01471327