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

NCT03014674 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2049582016-002405-19
• Study Type: interventional
• Target: 246
• Locations: 3 countries
• Sites: 3

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

Keywords

SB-240563; subcutaneous; lyophilized drug product; Mepolizumab; liquid drug product; safety syringe; auto injector

Outcome Measures

Primary Outcomes (2)

• Maximum Observed Plasma Concentration (Cmax) of Mepolizumab

  Blood samples were collected at indicated time points. Cmax following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with reconstituted lyophilized drug product from the vial. Pharmacokinetic (PK) Population comprised of all participants receiving study drug for whom a pharmacokinetic sample was obtained and analyzed.

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

• Area Under the Plasma Concentration Time Curve (AUC) From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-t]), AUC From Time Zero Extrapolated to Infinite Time (AUC[0-inf]) of Mepolizumab

  Blood samples were collected at indicated time points. AUC(0-t) and AUC(0-inf) following a single dose administration of liquid mepolizumab using a safety syringe and an autoinjector were compared with lyophilized drug product. Fixed effects analysis of covariance model was used for analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

Secondary Outcomes (17)

• Time to Cmax (Tmax) and Last Time Point Where the Concentration is Above the Limit of Quantification (Tlast) of Mepolizumab

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

• Apparent Clearance (CL/F) of Mepolizumab

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

• Apparent Volume of Distribution (Vd/F) of Mepolizumab

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

• Terminal Phase Elimination Rate Constant (Lambda z) of Mepolizumab

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

• Terminal Phase Half-life (t½) of Mepolizumab

  Day 1 (pre-dose, 2 hours, and 8 hours post-dose), Days 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 22, 29, 43, 57 and 85 post-dose

Study Arms (3)

Liquid mepolizumab in safety syringe

EXPERIMENTAL

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

Biological: Liquid mepolizumab; Device: Prefilled Safety Syringe

Liquid mepolizumab in an autoinjector

EXPERIMENTAL

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

Biological: Liquid mepolizumab; Device: Prefilled autoinjector

Lyophilised mepolizumab from vial

ACTIVE COMPARATOR

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

Biological: Lyophilized mepolizumab

Interventions

Lyophilized mepolizumab 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.

Lyophilised mepolizumab from vial

Liquid mepolizumab 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.

Liquid mepolizumab in an autoinjector; Liquid mepolizumab in safety syringe

Prefilled autoinjector 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.

Liquid mepolizumab in an autoinjector

Prefilled Safety Syringe DEVICE

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

Liquid mepolizumab in safety syringe

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (3)

GSK Investigational Site

Baltimore, Maryland, 21225, United States

Location

GSK Investigational Site

Berlin, 14050, Germany

Location

GSK Investigational Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 31317668 BACKGROUND

MeSH Terms

Conditions

Asthma

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: January 9, 2017
• Study Start: January 6, 2017
• Primary Completion: August 11, 2017
• Study Completion: August 11, 2017
• Last Updated: December 3, 2019
• Results First Posted: August 14, 2018

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1); DE (1); GB (1)