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

NCT04136145 | Completed Phase 1 Results

• 1 other identifier: 209629
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Serum Concentration of Belimumab Following Intravenous Administration

  Blood samples were collected at indicated time points for measurement of serum concentrations of belimumab following intravenous administration. Pharmacokinetic Population comprised of all safety participants (all randomized participants who received at least one dose of study treatment) for whom at least one evaluable pharmacokinetic sample was obtained and analyzed.

  Pre-dose (prior to start of belimumab IV infusion), 30 minutes (after the start of infusion), 0 hour (end of infusion); at 1, 6, 24, 48, 72, 96, 168, 336, 504, 672, 1008, 1344 and 1680 hours after end of infusion

• Serum Concentration of Belimumab Following Subcutaneous Administration

  Blood samples were collected at indicated time points for measurement of serum concentrations of belimumab following subcutaneous administration.

  Pre-dose and at 6 hours, 24 hours, 48 hours, 72 hours, 96 hours, 120 hours, 144 hours, 168 hours, 240 hours, 336 hours, 504 hours, 672 hours, 1008 hours, 1344 hours and 1680 hours post-dose

Secondary Outcomes (7)

• Number of Participants With Abnormal Vital Signs

  Up to Day 71

• Number of Participants With Abnormal Electrocardiogram (ECG) Findings

  Up to Day 71

• Number of Participants With Abnormal Clinical Chemistry Parameters

  Up to Day 71

• Number of Participants With Abnormal Hematology Parameters

  Up to Day 71

• Number of Participants With Abnormal Urinalysis Parameters

  Up to Day 71

Study Arms (2)

Belimumab SC

EXPERIMENTAL

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.

Drug: Belimumab for SC

Belimumab IV

EXPERIMENTAL

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

Drug: Belimumab for IV

Interventions

Belimumab for IV 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.

Belimumab IV

Belimumab for SC 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 SC

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Shanghai, 201508, China

Location

Related Publications (1)

• 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.

  PMID: 34554352 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; 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 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 1:2 ratio to receive one treatment of either IV or SC administration of belimumab 200 mg.

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: October 23, 2019
• Study Start: October 28, 2019
• Primary Completion: January 14, 2020
• Study Completion: January 14, 2020
• Last Updated: December 28, 2020
• Results First Posted: December 28, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• 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

CN (1)