Clinical trial NCT01583530: Study of Belimumab Administered Subcutaneously to Healthy Subjects
Official title: A Randomized, Parallel-Group, Open-Label Study to Evaluate the Absolute Bioavailability, Pharmacokinetics, Tolerability and Safety of a High Concentration Formulation of Belimumab (HGS1006), a Fully Human Monoclonal Anti-BLyS Antibody, Administered Subcutaneously to Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Belimumab
Injections, Subcutaneous
Drug Administration Routes
Injections
Lupus Erythematosus, Systemic
Lupus
SLE
Systemic Lupus Erythematosus
Antibodies
Autoimmune Disease
Biological Therapy
Immune System Diseases
Pharmacokinetics
Biological Availability
Lead sponsor: Human Genome Sciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2012-04-24
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the amount of belimumab in the blood when given as an injection under the skin (subcutaneously; SC) and to evaluate the safety and tolerability of multiple injections under the skin in healthy subjects.

Detailed description: This study is designed to evaluate the absolute bioavailability, pharmacokinetics, tolerability, and safety of a single dose (groups 1-4) or multiple doses (groups 5-6) of belimumab administered subcutaneously (SC) to healthy subjects.

Eligibility criteria: Key Inclusion Criteria:

* Healthy subjects defined as no clinically relevant abnormalities identified by a detailed medical history, full physical exam, 12-lead electrocardiogram (ECG), and clinical laboratory tests.
* Body weight between 45 to 120 kg (99 to 264 lbs).
* Must agree to use effective contraception throughout the study and for 14 weeks after administration of belimumab.
* Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.

Key Exclusion Criteria:

* Pregnant or nursing.
* Test positive for drugs or alcohol or have had a drug or alcohol dependence within the past year.
* Have used any prescription medicines within the past 30 days or herbal/botanical supplements within the past 7 days or anticipate use during the study. May use prescription contraceptives, hormone replacement therapy, and over-the-counter medicines such as antihistamines or nutritional support such as vitamins, minerals, or amino acids.
* Have received a live vaccine within the past 30 days or anticipate receipt of a live vaccine during the study and within 4 months after last injection of belimumab.
* Have a history of an allergic or anaphylactic reaction to drugs, food, or insect bite or sting requiring medical intervention.
* Have a history of allergic reaction to contrast agents or biological medicines.
* Have participated in a clinical trial and received an experimental medicine within the past 60 days.
* Have received treatment with a B cell targeted therapy at any time.
* Have required management of an infection within the past 14 days.

Primary outcomes:
measure: Time to Reach Maximum Serum Drug Concentration (Tmax) Following a Single Dose of Belimumab Given as Intravenous Infusion (IV) or Subcutaneous Injection (SC)
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
measure: Maximum Serum Drug Concentration (Cmax) Following a Single Dose of Belimumab Given as IV or SC
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
measure: Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following a Single Dose of Belimumab Given as IV or SC
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
measure: Terminal Elimination Half-life (t1/2,Term) Following a Single Dose of Belimumab Given as IV or SC
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
measure: Absolute Bioavailability of a Single Dose of Belimumab Given as IV or SC
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70
Secondary outcomes:
measure: Time to Reach Maximum Serum Drug Concentration (Tmax) Following Weekly (x 4) SC Injections of Belimumab
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119
measure: Maximum Serum Drug Concentration (Cmax) Following Weekly (x 4) SC Injections of Belimumab
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119
measure: Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following Weekly (x 4) SC Injections of Belimumab
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119
measure: Terminal Elimination Half-life (t1/2,Term) Following Weekly (x 4) SC Injections of Belimumab
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119
measure: Absolute Bioavailability of Weekly (x 4) SC Injections of Belimumab
timeFrame: Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 14, 21, 22, 23, 24, 25, 26, 27, 28, 31, 35, 42, 49, 63, 77, 91, and 119
measure: Number of Participants Who Experienced Adverse Events
timeFrame: Up to Day 119
Other outcomes:
Locations:
city: Daytona Beach
country: United States
state: Florida
city: Evansville
country: United States
state: Indiana
city: Dallas
country: United States
state: Texas
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gupta SV, Fanget MC, MacLauchlin C, Clausen VA, Li J, Cloutier D, Shen L, Robbie GJ, Mogalian E. Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection. Drugs R D. 2021 Dec;21(4):455-465. doi: 10.1007/s40268-021-00369-w. Epub 2021 Nov 6.
citation: Zhou X, Lee TI, Zhu M, Ma P. Prediction of Belimumab Pharmacokinetics in Chinese Pediatric Patients with Systemic Lupus Erythematosus. Drugs R D. 2021 Dec;21(4):407-417. doi: 10.1007/s40268-021-00363-2. Epub 2021 Oct 9.