Study of Belimumab Administered Subcutaneously to Healthy Subjects

NCT01583530 | Completed Phase 1 Results

• 1 other identifier: HGS1006-C1105
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (6)

• 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

  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

  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

  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

Study Arms (6)

Belimumab IV 240 mg

ACTIVE COMPARATOR

Biological: Single Dose Group: Belimumab IV 240 mg

Belimumab SC 2 x 120 mg

EXPERIMENTAL

Biological: Single Dose Group: Belimumab SC 2 x 120 mg

Belimumab SC 1 x 240 mg

EXPERIMENTAL

Biological: Single Dose Group: Belimumab SC 1 x 240 mg

Belimumab SC 1 x 200 mg

EXPERIMENTAL

Biological: Single Dose Group: Belimumab SC 1 x 200 mg

Belimumab SC 2 x 120 mg weekly

EXPERIMENTAL

Biological: Multiple Dose Group: Belimumab SC 2 x 120 mg weekly

Belimumab SC 1 x 200 mg weekly

EXPERIMENTAL

Biological: Multiple Dose Group: Belimumab SC 1 x 200 mg weekly

Interventions

Single Dose Group: Belimumab IV 240 mg BIOLOGICAL

Belimumab IV 240 mg administered on Day 0

Also known as: BENLYSTA™

Belimumab IV 240 mg

Single Dose Group: Belimumab SC 2 x 120 mg BIOLOGICAL

Belimumab SC 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Day 0

Also known as: BENLYSTA™

Belimumab SC 2 x 120 mg

Single Dose Group: Belimumab SC 1 x 240 mg BIOLOGICAL

Belimumab SC 240 mg x 1 injection on Day 0

Also known as: BENLYSTA™

Belimumab SC 1 x 240 mg

Single Dose Group: Belimumab SC 1 x 200 mg BIOLOGICAL

Belimumab SC 200 mg x 1 injection on Day 0

Also known as: BENLYSTA™

Belimumab SC 1 x 200 mg

Multiple Dose Group: Belimumab SC 2 x 120 mg weekly BIOLOGICAL

Belimumab 120 mg x 2 injections (equal to 240 mg) administered immediately one after the other on Days 0, 7, 14, and 21

Also known as: BENLYSTA™

Belimumab SC 2 x 120 mg weekly

Multiple Dose Group: Belimumab SC 1 x 200 mg weekly BIOLOGICAL

Belimumab 200 mg x 1 injection administered on Days 0, 7, 14, and 21

Also known as: BENLYSTA™

Belimumab SC 1 x 200 mg weekly

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Human Genome Sciences Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (4)

Unknown Facility

Daytona Beach, Florida, United States

Location

Unknown Facility

Evansville, Indiana, United States

Location

Unknown Facility

Dallas, Texas, United States

Location

Unknown Facility

Madison, Wisconsin, United States

Location

Related Publications (2)

• 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.

  PMID: 34741731 DERIVED

• 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.

  PMID: 34628605 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Autoimmune Diseases; Immune System Diseases

Interventions

belimumab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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

Study Record Dates

• First Submitted: April 20, 2012
• First Posted: April 24, 2012
• Study Start: February 1, 2011
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: August 7, 2013
• Results First Posted: August 28, 2012

Record last verified: 2013-08

Locations

US (4)