Belimumab Phase I Study in Chinese Subjects With Systemic Lupus Erythematosus

NCT02880852 | Completed Phase 1 Results

• 1 other identifier: 200909
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

In China, Belimumab (GSK1550188) will be developed for a dosing regimen of once-monthly intravenous (IV) infusion for the treatment of SLE. This open-label, single dose study will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of belimumab in Chinese SLE subjects. A total of approximately 20 subjects will be enrolled to receive IV infusion of 10 milligrams per kilogram (mg/kg) GSK1550188 on Day 0 for the treatment of SLE. Subjects will be followed for 84 days after the administration of drug.

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus; Belimumab; Pharmacodynamics; safety tolerability; Pharmacokinetics; Chinese subjects

Outcome Measures

Primary Outcomes (7)

• Maximum Observed Concentration (Cmax) of Belimumab

  Blood samples were collected at the indicated timepoints to calculate Cmax of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0 to t]) and Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0 to Inf]) of Belimumab

  Blood samples were collected at the indicated timepoints to calculate AUC (0 to t) and AUC (0 to inf) of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Terminal Phase Half-life (t1/2) of Belimumab

  Blood samples were collected at the indicated time points to calculate t1/2 of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Terminal Phase Rate Constant (Lambda z) of Belimumab

  Blood samples were collected at the indicated time points to calculate lambda z of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Systemic Clearance (CL) of Belimumab

  Blood samples were collected at the indicated time points to calculate CL of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Volume of Distribution (Vz) of Belimumab

  Blood samples were collected at the indicated time points to calculate Vz of belimumab.

  Day 0 (pre-dose, 5 minutes, 1 hour, 6 hours, 24 hours), and on Days 1, 7, 14, 21, 28, 42, 56, and 84 post-dose

• Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

  AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant, or associated with liver injury and impaired liver function.

  Up to Day 84

Secondary Outcomes (16)

• Change From Baseline to Day 84 in Vital Signs- Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline (pre-dose on Day 0) to Day 84

• Change From Baseline to Day 84 in Vital Sign- Pulse Rate

  Baseline (pre-dose on Day 0) to Day 84

• Change From Baseline to Day 84 in Vital Sign- Temperature

  Baseline (pre-dose on Day 0) to Day 84

• Number of Participants With Abnormal-clinically Significant 12-lead Electrocardiogram (ECG) Findings

  Up to Day 84

• Change From Baseline to Day 84 in Clinical Chemistry Parameters- Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrogenase

  Baseline (pre-dose on Day 0) to Day 84

Study Arms (1)

Belimumab 10 mg/kg

EXPERIMENTAL

In this open label study, a single dose of 10 mg/kg Belimumab will be administered intravenously in Chinese subjects with systemic lupus erythematosus.

Drug: Belimumab

Interventions

Belimumab DRUG

Belimumab will be provided as white uniform lyophilized cake in vials with unit dose strength of 400 mg/vial plus excipients (citric acid/sodium citrate/sucrose/polysorbate) for reconstitution in 4.8 milliliter sterile water for injection (SWFI). Belimumab will be administered as 10 mg/kg intravenous infusion for over 1 hour on Day 0.

Belimumab 10 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who give consent to this study participation and sign informed consent form.
• Subjects at least 18 years of age inclusive at screening visit.
• SLE Classification: Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) classification criteria, with 4 or more of the 11 ACR criteria present, serially or simultaneously during any interval or observation.
• SLE Treatment: Be on either no SLE medication or a stable SLE treatment regimen of any medication (alone or in combination) for a period of at least 2 months prior to Day 0; corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day); immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), mizoribine, calcineurin inhibitors (example \[e.g.\], tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, or thalidomide; anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine) and non-steroidal anti-inflammatory drugs (NSAIDs).
• The subjects with positive test for anti-nuclear antibody (ANA) or anti-double stranded deoxyribonucleic acid (DNA) serum antibody.
• Males and females: A female subject is eligible to enter the study if she is: not pregnant or nursing; of non-childbearing potential (i.e., women who had a hysterectomy, are postmenopausal which is defined as 1 year without menses, have both ovaries surgically removed or have current documented tubal ligation); of childbearing potential (i.e., women with functional ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category includes women with oligomenorrhoea \[even severe\], women who are perimenopausal or have just begun to menstruate. These women must have a negative serum pregnancy test at screening, and agree to one of the following: complete abstinence from penile-vaginal intercourse, when this is the female's preferred and usual lifestyle, from 2 weeks prior to administration of the 1st dose of investigational product (IP) until study complete; or consistent and correct use of one of the following acceptable methods of birth control for 1 month prior to the start of the IP and for 16 weeks after the last dose of IP: any intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1 percent (%) per year; oral contraceptives; double barrier method with vaginal spermicidal agent: condom and an occlusive cap (cervical cap/vault or diaphragm) with a vaginal spermicidal agent (foam/gel/film/cream/suppository); implants of etonogestrel or levonorgestrel; estrogenic vaginal ring; injectable progesterone; percutaneous contraceptive patch; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subject.
• Based on single or averaged corrected QT (QTc) interval values of triplicate ECGs obtained over a brief recording period: \[QTc corrected by Bazett's (QTcB) or QTc corrected by Fridericia's (QTcF) formula\] \<450 milliseconds (msec); or QTcB or QTcF \<480 msec in subjects with bundle branch block.

You may not qualify if:

• B-cell Therapy: Have received treatment with any B cell targeted therapy (e.g., rituximab, other anti-CD20 agents, anti-CD22 \[epratuzumab\], anti-CD52 \[alemtuzumab\], BLyS-receptor fusion protein \[BR3\], Transmembrane activator and calcium-modulator and cytophilin ligand interactor \[TACI\] Fc, or belimumab) at any time.
• The subject has received a biologic investigational or non-investigational agent within 12 months prior to Day 0.
• Received IV immunoglobulin (Ig), plasmapheresis, hemodialysis, intravenous cyclophosphamide, or high dose prednisone and its equivalents (\>60 mg/day) within 6 months prior to Day 0.
• The subject has received a non-biologic investigational agent within 2 months prior to Day 0.
• The subject is currently participating in another clinical study or post-marketing study in which the subject is or will be exposed to an investigational agent.
• The subject has severe lupus kidney disease (defined by proteinuria \>6 grams \[g\]/24 hours) within 6 months prior to the Screening visit.
• History of renal transplant.
• Active central nervous system (CNS) lupus \[including seizures, psychosis, organic brain syndrome, cerebrovascular accident (CVA), motor neuropathy, vasculitis\] requiring medical intervention within 6 months prior to Screening visit.
• Infections: Have required management of acute or chronic infections, as follows: currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); hospitalization for treatment of infection within 2 months prior to Day 0; use of parenteral (IV or intramuscular \[IM\]) antibiotics (antibacterials, antivirals, anti-fungals, or anti parasitic agents) within 2 months prior to Day 0.
• The subject has hypogammaglobulinemia or immunoglobulin A (IgA) deficiency (IgA level \<10 mg/deciliter \[dL\]).
• Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
• Uncontrolled other diseases: History or clinical evidence of active significant acute or chronic diseases (i.e., cardiovascular, pulmonary, untreated hypertension, anemia, gastrointestinal, hepatic, renal, neurological, cancer, or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the subject at undue risk.
• Have a planned surgical procedure, or a history of any other medical disease, or laboratory abnormalities, or conditions which would make the subject (in the opinion of the Investigator) unsuitable for the study.
• The subject has an abnormality on 12-lead ECG at screening which is clinically significant in the opinion of the investigator.
• Have evidence of current drug or alcohol abuse or dependence.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Shanghai, China

Location

GSK Investigational Site

Suzhou, 215004, China

Location

Related Publications (3)

• Zhang J, Wan W, Miao L, Wu J, Dong J, Shen Y, Xiong C, Li C, Xue Y, Cao G, Ma P. Pharmacokinetics, Pharmacodynamics and Safety of Belimumab in Chinese Patients with Systemic Lupus Erythematosus: A Phase I, Open-Label Study. Rheumatol Ther. 2020 Mar;7(1):191-200. doi: 10.1007/s40744-020-00193-9. Epub 2020 Jan 17.

  PMID: 31953740 BACKGROUND

• 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

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: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: January 23, 2017
• Primary Completion: September 8, 2017
• Study Completion: September 8, 2017
• Last Updated: March 27, 2020
• Results First Posted: November 9, 2018

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• 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 (2)