Clinical trial NCT04136145: 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
Official title: An Open-label, Randomized, Parallel Group, Single Dose Study to Investigate the PK and Safety of Belimumab 200 mg Intravenous and 200 mg Subcutaneous Via Auto-injector in Chinese Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Systemic Lupus Erythematosus
Keywords: belimumab
Chinese
intravenous
subcutaneous
auto-injector
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-10-23
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized in a 1:2 ratio to receive one treatment of either IV or SC administration of belimumab 200 mg.
Primary purpose: TREATMENT

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.


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.
* Healthy as defined as being free from clinically significant illness or disease as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital sign, laboratory tests and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied, may be included only if the investigator (in consultation with the GlaxoSmithKline (GSK) medical monitor if necessary) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Serum Concentration of Belimumab Following Intravenous Administration
timeFrame: 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
measure: Serum Concentration of Belimumab Following Subcutaneous Administration
timeFrame: 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:
measure: Number of Participants With Abnormal Vital Signs
timeFrame: Up to Day 71
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
timeFrame: Up to Day 71
measure: Number of Participants With Abnormal Clinical Chemistry Parameters
timeFrame: Up to Day 71
measure: Number of Participants With Abnormal Hematology Parameters
timeFrame: Up to Day 71
measure: Number of Participants With Abnormal Urinalysis Parameters
timeFrame: Up to Day 71
measure: Number of Participants With Injection Site Reaction
timeFrame: Up to Day 71
measure: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events
timeFrame: Up to Day 71
Other outcomes:
Locations:
city: Shanghai
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.