A Study to Compare the Pharmacokinetics of Mepolizumab as a Liquid Drug in a Safety Syringe or an Autoinjector Versus Lyophilised Drug

NCT ID: NCT03014674

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 246 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-06
• Study Completion Date: 2017-08-11

Brief Summary

Mepolizumab (SB-240563) is a humanized monoclonal antibody (Immunoglobulin G1, kappa, mAb) that blocks human interleukin-5 (hIL-5) from binding to the interleukin (IL)-5 receptor complex expressed on the eosinophil cell surface and thus inhibits signaling. This study will compare the pharmacokinetics and safety of mepolizumab administered as a liquid drug product in two different devices with the reconstituted lyophilized drug product in healthy subjects. Subjects will receive a single administration of 100 milligram (mg) mepolizumab as a single injection. The randomization will be stratified by body weight (<70 kilogram (kg), 70 <80 kg and >=80 kg) and the site of injection will be randomized 1:1:1 to the upper arm, abdomen or thigh. Approximately 243 healthy subjects will be randomized so that at least 9 subjects are randomized to each mepolizumab treatment within each weight strata and 3 subjects within each mepolizumab treatment, weight strata and injection site. Each subject will participate in the study for up to approximately 16 weeks (up to 85 days after drug administration), and will have a screening visit, a single dose treatment period, and a follow-up visit.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Liquid mepolizumab in safety syringe

Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled syringe within a safety syringe according to randomization.

Group Type: EXPERIMENTAL

Liquid mepolizumab

Intervention Type: BIOLOGICAL

Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.

Prefilled Safety Syringe

Intervention Type: DEVICE

Single use, disposable safety syringe with a retracting needle guard and locking system.

Liquid mepolizumab in an autoinjector

Subjects will receive a single dose of 100 mg liquid mepolizumab administered subcutaneously using a prefilled autoinjector, according to randomization.

Group Type: EXPERIMENTAL

Liquid mepolizumab

Intervention Type: BIOLOGICAL

Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.

Prefilled autoinjector

Intervention Type: DEVICE

Single use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product. It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device. Start and end of injection clicks will inform the user of correct use. A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries.

Lyophilised mepolizumab from vial

Subjects will receive a single dose of 100 mg reconstituted lyophilized mepolizumab manually administered subcutaneously according to randomization

Group Type: ACTIVE_COMPARATOR

Lyophilized mepolizumab

Intervention Type: BIOLOGICAL

Mepolizumab will be provided as white, uniform, lyophilized cake in vials with unit dose strength of 100 mg/vial for reconstitution in 1.2 mL sterile water for injection (SWFI). Following reconstitution it forms a clear to opalescent, colorless to pale yellow solution for SC injection.

Interventions

Lyophilized mepolizumab

Mepolizumab will be provided as white, uniform, lyophilized cake in vials with unit dose strength of 100 mg/vial for reconstitution in 1.2 mL sterile water for injection (SWFI). Following reconstitution it forms a clear to opalescent, colorless to pale yellow solution for SC injection.

Intervention Type: BIOLOGICAL

Liquid mepolizumab

Mepolizumab will be provided as a clear to opalescent, colorless to pale yellow sterile solution for SC injection, supplied in a single-use, prefilled autoinjector or safety syringe containing 100 mg/mL mepolizumab with sodium phosphate, citric acid, sucrose ethylenediaminetetraacetic acid and polysorbate 80.

Intervention Type: BIOLOGICAL

Prefilled autoinjector

Single use, disposable autoinjector will be assembled with the prefilled syringe containing the drug product. It will enable automatic delivery of the drug product under the power of a spring mechanism following activation of the device. Start and end of injection clicks will inform the user of correct use. A plastic needle will cover shield the needle before and after injection to minimize the potential for needle stick injuries.

Intervention Type: DEVICE

Prefilled Safety Syringe

Single use, disposable safety syringe with a retracting needle guard and locking system.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 18 years of age and over at the time of signing the informed consent.

Exclusion Criteria

• Body weight >=50 kg and body mass index (BMI) within the range 19.0-30 kg/square meter(m^2) (inclusive)
• Male or Female: A female subject is eligible to participate if she is not pregnant (as confirmed by a negative human chorionic gonadotrophin (hCG) test), not lactating, and at least one of the following conditions applies: Non-reproductive potential defined as: pre-menopausal females with documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; hysterectomy; documented bilateral oophorectomy; post- menopausal females. Subject is of reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication and until 16 weeks after the administration of the single dose of study medication.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in the protocol. The subject must be able to understand and communicate in the native language of the site, e.g. German in German sites.

• Alanine transaminase >1.5x upper limit of normal (ULN)
• Bilirubin >1.5xULN (isolated bilirubin >1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• QTc corrected by Fridericia's (QTcF) formula>450 milliseconds (msec)
• Any clinically relevant abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or 12-lead electrocardiogram.
• 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) before the first dose of study medication and until study completion, unless in the opinion of the investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units for females and >21 units for males. One unit is equivalent to 8 grams of alcohol: a half-pint (~240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
• Urinary nicotine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. Limit of >500 nanogram/mL.
• Involved in any activities likely to result in any significant decrease or increase in body weight during the study period (e.g. 'crash' dieting, bodybuilding).
• 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 Medical Monitor, contraindicates their participation.
• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
• A positive test for human immunodeficiency virus antibody.
• Subjects with known, pre-existing helminthes infestation within 6 months prior to Day 1.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 3 months.
• 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.
• A positive pre-study drug/alcohol screen.
• A vulnerable subject. Defined as individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
• Subjects who work for the Sponsor, contract research organization, or one of the study centers.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Harrow, Middlesex, United Kingdom

Countries

United States; Germany; United Kingdom

References

Shabbir S, Pouliquen IJ, Bentley JH, Bradford ES, C Kaisermann M, Albayaty M. The Pharmacokinetics and Relative Bioavailability of Mepolizumab 100 mg Liquid Formulation Administered Subcutaneously to Healthy Participants: A Randomized Trial. Clin Pharmacol Drug Dev. 2020 Apr;9(3):375-385. doi: 10.1002/cpdd.726. Epub 2019 Jul 17.

Reference Type: BACKGROUND

PMID: 31317668 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-002405-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

204958

Identifier Type: -

Identifier Source: org_study_id