Single Dose Study to Investigate the Pharmacokinetics (PK) and Safety of Belimumab 200 Milligrams (mg) Intravenous and 200 mg Subcutaneous Via Auto-injector in Chinese Healthy Subjects

NCT ID: NCT04136145

Last Updated: 2020-12-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-28
• Study Completion Date: 2020-01-14

Brief Summary

This is an open-label, randomized, parallel group, single dose study in healthy Chinese subjects. The purpose of this study is to characterize the pharmacokinetic profile and safety profile of 200 mg single dose of belimumab, administered either intravenously or subcutaneously via auto-injector. Each subject will be randomized in a 1:2 ratio to receive a single dose of either intravenous (IV) or subcutaneous (SC) administration of belimumab 200 mg. The total study duration will be approximately 13 weeks.

Conditions

Systemic Lupus Erythematosus

Keywords

belimumab; Chinese; intravenous; subcutaneous; auto-injector

Study Design

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

Study Groups

Belimumab SC

Subjects will be administered a single dose of belimumab 200 mg via the SC route. The dose will be administered in the front of the thigh via auto-injector device.

Group Type: EXPERIMENTAL

Belimumab for SC

Intervention Type: DRUG

Belimumab will be available as clear to opalescent, colorless to pale yellow sterile solution at unit dose strength of 200 mg/milliliter (mg/mL) for SC injection in a single-use, prefilled syringe contained within an auto-injector device.

Belimumab IV

Subjects will be administered a single dose of belimumab 200 mg via the IV route administered over approximately 1 hour.

Group Type: EXPERIMENTAL

Belimumab for IV

Intervention Type: DRUG

Belimumab will be available as white to off-white lyophilized cake at a unit dose strength of 400 mg to be reconstituted and diluted in normal saline to obtain 200 mg per dose.

Interventions

Belimumab for IV

Belimumab will be available as white to off-white lyophilized cake at a unit dose strength of 400 mg to be reconstituted and diluted in normal saline to obtain 200 mg per dose.

Intervention Type: DRUG

Belimumab for SC

Belimumab will be available as clear to opalescent, colorless to pale yellow sterile solution at unit dose strength of 200 mg/milliliter (mg/mL) for SC injection in a single-use, prefilled syringe contained within an auto-injector device.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
• Chinese healthy male or female between 18 and 45 years of age inclusive, at the time of signing the informed consent.

Exclusion Criteria

• Non-smoker or ex-smoker having ceased smoking for at least 6 months.
• Body weight >=45.0 kilograms (kg) for females, >=50.0 kg for males, and body mass index (BMI) within the range 19.0<= to <=26.0 kilograms per meter square (kg/m^2).
• Both male and female subjects are eligible to participate.
• A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: i) Not a woman of childbearing potential (WOCBP) OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of belimumab.

• A positive test for syphilis, positive Hepatitis C antibody, human immune deficiency syndrome (HIV) antigen/antibody, at Screening. For Hepatitis B: subjects with a positive hepatitis B surface antigen (HbsAg) and/or a positive anti-hepatitis B core (HBc) result will be excluded.
• A positive result of pre-study drug screen (including at minimum: amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines).
• ALT or AST >1.2 times upper limit of normal (ULN).
• Bilirubin >1.2 times ULN (isolated bilirubin >1.2 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• QTc >450 milliseconds (msec) based on single ECG. The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine read or manually over-read.
• Immunoglobulin (M, A, G) level is <Lower limit of normal (LLN) at Screening.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• History of major organ transplant: e.g., heart, lung, kidney, liver, or hematopoietic stem cell transplant.
• History of malignant neoplasm within the last 5 years, except for adequately treated basal or squamous cell cancers of the skin, or carcinoma in situ of the uterine cervix.
• Subjects with a sitting position systolic blood pressure <90 millimeters of mercury (mmHg) or >=140 mmHg and/or a sitting diastolic blood pressure <50 mmHg or >=90 mmHg and/or systolic blood pressure drop from supine to standing of >30 mmHg.
• Symptomatic herpes zoster within 3 months prior to Screening.
• Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posteroanterior) and a positive (not indeterminate) QuantiFERON-TB Gold test.
• History of any infection requiring hospitalization or treatment with antivirals, antibiotics, anti-fungals, anti-parasitic agents or vaccination within 30 days prior to the administration of study medication.
• History of regular alcohol consumption exceeding, on an average, 14 drinks/week for men or 7 drinks/week for female (1 drink = 5 ounces [150 mL] of wine or 350 mL of beer or 1.5 ounces [45 mL] of 80 proof distilled spirits) within 6 months of Screening.
• The subject had participated in a clinical study or post-marketing study with an investigational or a non-investigational product during the previous 4 months or 5 half-lives (whichever is longer) preceding the administration of study medication of this study.
• Exposure to more than 4 new chemical entities within 12 months prior to the dosing day.
• The subject planned to concurrently participate in another clinical study or post marketing study.
• Use of any prescription or non-prescription medications including vitamins, herbal and dietary supplements within the 14 days or 5 half-lives (whichever is longer) prior to the administration of study medication.
• History of B cell targeted therapy (rituximab, other anti-cluster of differentiation (CD)20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], B lymphocyte stimulator (BlyS)-receptor fusion protein [BR3], Transmembrane activator and calcium-modulator and cytophilin ligand interactor (TACI)-fusion (Fc), LY2127399 [anti-B cell-activating factor receptor (BAFF)] or belimumab) at any time.
• Have received a live vaccine within 30 days of Day 1 or anticipate receipt of a live vaccine during the study or within 120 days after the last dose administration of study drug.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy (excluding pollen allergy) without current symptoms.
• History of anaphylactic reaction to any food, drug, or insect bite/sting.
• History of allergic reaction to parenteral administration of contrast agents, foreign proteins, or monoclonal antibodies.
• Donation of blood or blood products or significant blood loss in excess of 400 mL within 4 months or 200 mL within 2 months prior to administration
• Subject is mentally or legally incapacitated, or unwillingness or inability (including mentally or legally incapacity) to follow the procedures outlined in the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 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

Shanghai, , China

Countries

China

References

Meng X, Wang Q, Wu S, Pu D, Zhang A, Fang S, Zhou X, Lu H. Pharmacokinetics and Safety of Intravenous and Subcutaneous Auto-injector Single-dose Belimumab in Healthy Chinese Volunteers: A phase 1, Randomized, Open-label Study. Rheumatol Ther. 2021 Dec;8(4):1711-1724. doi: 10.1007/s40744-021-00366-0. Epub 2021 Sep 23.

Reference Type: DERIVED

PMID: 34554352 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

209629

Identifier Type: -

Identifier Source: org_study_id