Japanese Phase 1 Study of Mepolizumab

NCT01471327 | Completed Phase 1

• 1 other identifier: 115705
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Outcome Measures

Primary Outcomes (2)

• pharmacokinetics

  Cmax, AUC

  From Day 1 to Follow-Up(Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)

• Safety

  vital signs, ECGs, clinical laboratory tests and adverse events

  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 (3)

• blood eosinophil counts

  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

  From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)

• immunogenicity

  From Day 1 to Follow-Up (Days 85 for Cohort 1 and 2, Days 121 for Cohort 3, Days 151 for Cohort 4)

Study Arms (5)

SB-240563, 10mg

EXPERIMENTAL

IV, single dose at Day 1

Biological: SB-240563

Placebo

EXPERIMENTAL

Saline IV, single dose at Day 1

Other: Placebo

SB-240563, 75mg

EXPERIMENTAL

IV, single dose at Day 1

Biological: SB-240563

SB-240563, 250mg

EXPERIMENTAL

IV, single dose at Day 1

Biological: SB-240563

SB-240563, 750mg

EXPERIMENTAL

IV, single dose at Day 1

Biological: SB-240563

Interventions

SB-240563 BIOLOGICAL

10mg, 75mg, 250mg and 750mg IV, single dose on Day 1

SB-240563, 10mg; SB-240563, 250mg; SB-240563, 750mg; SB-240563, 75mg

Placebo OTHER

Saline IV, single dose at Day 1

Placebo

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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%).

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

Related Publications (8)

• 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.

  PMID: 2653458 BACKGROUND

• 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.

  PMID: 19264686 BACKGROUND

• 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.

  PMID: 2022726 BACKGROUND

• 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.

  PMID: 9309982 BACKGROUND

• 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.

  PMID: 8360390 BACKGROUND

• 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.

  PMID: 21348536 BACKGROUND

• 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.

  PMID: 2659368 BACKGROUND

• 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.

  PMID: 11359633 BACKGROUND

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
• Results for study 115705 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Asthma

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: November 15, 2011
• Study Start: August 9, 2011
• Primary Completion: April 27, 2012
• Study Completion: April 27, 2012
• Last Updated: June 20, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)