Belimumab Phase I Study in Chinese Subjects With Systemic Lupus Erythematosus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Belimumab
Intervention description: 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.
Intervention MeSH terms: Belimumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Systemic Lupus Erythematosus; Belimumab; Pharmacodynamics; safety tolerability; Pharmacokinetics; Chinese subjects

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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.

          -  AST and ALT >=2x upper limit of normal (ULN); ALP and bilirubin >1.5xULN (isolated
             bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin
             <35%).

          -  Have a historically positive human immunodeficiency virus (HIV) test or test positive
             at screening for HIV.

          -  History of or positive test at screening visit for any of Hepatitis B surface antigen
             (HBsAg), anti- Hepatitis B core antibody (HBcAb) or anti-hepatitis C virus antibodies
             (HCVAb). If only anti-HBcAb result is positive, hepatitis B virus (HBV)-(DNA) test
             will be performed. If HBV-DNA results in negative, the patient is eligible.

          -  Laboratory Abnormalities: Have a Grade 3 or greater laboratory abnormality based on
             the protocol toxicity scale except for the following that are allowed:

          -  Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.

          -  Stable Grade 3/4 proteinuria (=<6 g/24 hour equivalent by spot urine protein to
             creatinine ratio allowed).

          -  Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver
             disease or malnutrition.

          -  Stable Grade 3 neutropenia or stable Grade 3 white blood cell count.

          -  Subjects who have evidence of serious suicide risk including any history of suicidal
             behavior in the last 6 months or who, in the investigator's opinion, pose a
             significant suicide risk.