Study of Belimumab Administered Subcutaneously to Healthy Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Biological: Single Dose Group: Belimumab IV 240 mg
* Biological: Single Dose Group: Belimumab SC 2 x 120 mg
* Biological: Single Dose Group: Belimumab SC 1 x 240 mg
* Biological: Single Dose Group: Belimumab SC 1 x 200 mg
* Biological: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly
* Biological: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Belimumab IV 240 mg<br> | Biological: Single Dose Group: Belimumab IV 240 mg<br>* Belimumab IV 240 mg administered on Day 0<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab SC 2 x 120 mg<br> | Biological: Single Dose Group: Belimumab SC 2 x 120 mg<br>* Belimumab SC 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Day 0<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab SC 1 x 240 mg<br> | Biological: Single Dose Group: Belimumab SC 1 x 240 mg<br>* Belimumab SC 240 mg x 1 injection on Day 0<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab SC 1 x 200 mg<br> | Biological: Single Dose Group: Belimumab SC 1 x 200 mg<br>* Belimumab SC 200 mg x 1 injection on Day 0<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab SC 2 x 120 mg weekly<br> | Biological: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly<br>* Belimumab 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Days 0, 7, 14, and 21<br>* Other names: BENLYSTA™;|
| Experimental: Belimumab SC 1 x 200 mg weekly<br> | Biological: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly<br>* Belimumab 200 mg x 1 injection administered on Days 0, 7, 14, and 21<br>* Other names: BENLYSTA™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Serum Drug Concentration (Tmax) Following a Single Dose of Belimumab Given as Intravenous Infusion (IV) or Subcutaneous Injection (SC) |  | Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 | 
| Maximum Serum Drug Concentration (Cmax) Following a Single Dose of Belimumab Given as IV or SC |  | Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 | 
| 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 | AUC (0-∞) = Area under the serum drug concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-last) plus C (last)/λz. C (last) is the last measurable concentration. λz was determined by linear regression (r2 ≥ 0.8) with uniform weighting of all data in the terminal linear portion of the log-transformed drug concentration-time profile. | Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 | 
| Terminal Elimination Half-life (t1/2,Term) Following a Single Dose of Belimumab Given as IV or SC | Terminal elimination half-life is the time measured for the serum drug concentration of belimumab to decrease by one half. | Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 | 
| Absolute Bioavailability of a Single Dose of Belimumab Given as IV or SC | Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. The bioavailability of belimumab administered by IV is compared to the bioavailability of belimumab administered via single-SC injection. | Pre-dose, Post-dose on Days 0, 1, 2, 3, 4, 5, 6, 7, 10, 14, 21, 28, 42, 56, and 70 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach Maximum Serum Drug Concentration (Tmax) Following Weekly (x 4) SC Injections of Belimumab |  | 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 | 
| Maximum Serum Drug Concentration (Cmax) Following Weekly (x 4) SC Injections of Belimumab |  | 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 | 
| Area Under the Serum Drug Concentration-time Curve From Time 0 to Infinite Time (AUC0-∞) Following Weekly (x 4) SC Injections of Belimumab | AUC (0-∞) = Area under the serum drug concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-last) plus C (last)/λz. C (last) is the last measurable concentration. λz was determined by linear regression (r2 ≥ 0.8) with uniform weighting of all data in the terminal linear portion of the log-transformed drug concentration-time profile. | 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 | 
| Terminal Elimination Half-life (t1/2,Term) Following Weekly (x 4) SC Injections of Belimumab | Terminal elimination half-life is the time measured for the serum drug concentration of belimumab to decrease by one half. | 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 | 
| Absolute Bioavailability of Weekly (x 4) SC Injections of Belimumab | Bioavailability (F) is a measurement of the rate and extent to which a drug reaches the systemic circulation. The bioavailability following weekly (x 4) SC injections of belimumab was calculated by comparing the bioavailability of belimumab administered IV to the bioavailability of belimumab administered via 4 weekly SC injections. | 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 | 
| Number of Participants Who Experienced Adverse Events | Includes AEs reported in participants from the first dose of belimumab throughout the study through Day 70/Exit (single dose groups) or Day 119/Exit (multiple dose groups). | Up to Day 119 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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