The Evaluation of Belimumab in Myasthenia Gravis (MG)
Condition: Myasthaenia Gravis
MeSH terms: Myasthenia Gravis
Intervention: Belimumab; Placebo
Intervention description: 10mg/kg IV infusion; placebo IV infusion
Intervention MeSH terms: Belimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Study BEL115123 is a randomized, placebo-controlled, double-blind, multinational study of
      belimumab (10 mg/kg) to investigate the efficacy and safety of belimumab in subjects with MG.
      The study will enroll male and female outpatients (> or equal to 18 years of age) with a
      diagnosis of MG who are 1) acetylcholine receptor (AChR) antibody positive or muscle specific
      kinase (MuSK) antibody positive, 2) on current standard of care therapy, and 3) continue to
      exhibit signs of MG. The study will include 3 phases: a 4 week screening period, a 24 week
      treatment period, and a 12 week follow-up period. IP will be administered intravenously on
      Days 0, 14, 28 and then every 28 days through and including Week 20. At Week 24, primary
      outcomes will be obtained. Follow up evaluations will be conducted at Weeks 28, 32 and 36 for
      all subjects. The primary objective of this study is to assess the efficacy of belimumab as
      evaluated by the change in the quantitative myasthenia gravis (QMG) score.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years and older, with life expectancy of greater than 1 year.

          -  MG of class II to IVa inclusive.

          -  Acetylcholine receptor (AChR) or muscle specific kinase (MuSK) antibody positive.

          -  Stable dose (defined as no dose changes) not exceeding the maximum doses given in
             Section 5.6.1 of the following therapy(ies) prior to screening: Cholinesterase
             inhibitor(pyridostigmine or equivalent) for at least 2 weeks prior to screening and no
             immunosuppressants; Cholinesterase inhibitor (pyridostigmine or equivalent) for at
             least 2 weeks prior to screening and/or only one of the following: prednisone (up to
             40 mg/day or equivalent) for at least 1 month prior to screening; azathioprine for at
             least 6 months prior to screening; mycophenolate for at least 6 months prior to
             screening, or cyclosporine for at least 3 months prior to screening; or Cholinesterase
             inhibitor (pyridostigmine or equivalent) for at least 2 weeks prior to screening
             and/or prednisone (up to 20 mg/day or equivalent) for at least 1 month prior to
             screening and only one of the following: azathioprine for at least 6 months prior to
             screening, mycophenolate for at least 6 months prior to screening, or cyclosporine for
             at least 3 months prior to screening

          -  Quantitative Myasthenia Gravis (QMG) score of 8 or greater, with at least 4 points
             derived from signs other than ocular

          -  A female subject is eligible to participate if she is: Of non-childbearing potential;
             Of childbearing potential and NOT pregnant or nursing, has a negative serum pregnancy
             test at screening, and agrees to one of the following: Complete abstinence from
             penile-vaginal intercourse, when this is the female's preferred and usual lifestyle,
             for the period from consent into the study until 16 weeks after the last dose of
             investigational product; or Consistent and correct use of one of the following
             acceptable methods of birth control for the period from consent into the study until
             16 weeks after the last dose of investigational product: Oral contraceptives (either
             combined or progesterone only), Injectable progesterone, Implants of etonogestrel or
             levonorgestrel, Estrogenic vaginal ring, Percutaneous contraceptive patches,
             Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate
             of less than 1% per year, Male partner sterilization (vasectomy with documentation of
             azoospermia) prior to the female subject's entry into the study; this male must be the
             sole partner for the subject, Double barrier method: condom and an occlusive cap
             (diaphragm or cervical/vault caps) with a vaginal spermicidal agent
             (foam/gel/film/cream/suppository).

          -  Capable of giving written informed consent, which includes compliance with the
             requirements and restrictions listed in the consent form.

          -  Single QTc less than 450 msec; or QTc less than 480 msec in subjects with Bundle
             Branch Block.

          -  AST and ALT less than 2xULN; alkaline phosphatase and bilirubin less or = to 1.5xULN
             (isolated bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated
             and direct bilirubin less than 35%).

        Exclusion Criteria:

          -  Participated in a clinical trial and has received an investigational product within 30
             days, 5 half-lives or twice the duration of the biological effect of the
             investigational product (whichever is longer) prior to screening or planning to take
             any investigational drug for the planned duration of study participation (6 months
             after the last dose of study drug).

          -  Presence or previous history of thymoma.

          -  Thymectomy within 12 months

          -  Clinically significant (in the opinion of investigator) abnormal laboratory values.

          -  Pregnant females as determined by positive (serum) hCG test at screening or prior to
             dosing, or lactating females or planning to become pregnant within 16 weeks after last
             dose of investigational product.

          -  History of sensitivity to any of the study medications, or components thereof or a
             history of drug or other allergy that, in the opinion of the investigator or GSK
             Medical Monitor, contraindicates their participation.

          -  May require (in the opinion of investigator) treatment with IVIg and/or plasmapheresis
             during the 24 week treatment period.

          -  Have received IVIg and/or plasmapheresis within 90 days prior to screening.

          -  Have received any other biopharmaceutical agent (except IVIg as described in exclusion
             criteria #8) in the 364 days prior to screening.

          -  Have received treatment with any B cell targeted therapy (e.g., rituximab, belimumab),
             at any time.

          -  Have received a live vaccine within 30 days of study Day 0 (baseline).

          -  Have received cyclophosphamide or any other immunosuppressive agent apart from the
             ones allowed by the inclusion criteria #4, within the past 6 months.

          -  Have another medical condition that requires treatment with steroids or
             immunosuppressive agents.

          -  Hospitalization due to infection or use of parenteral antibacterial, antifungal or
             antiviral agents within 60 days prior to screening; or history of recurrent or chronic
             infection, or currently active systemic infection.

          -  Have a history of malignant neoplasm within the last 5 years, except for adequately
             treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the
             uterine cervix.

          -  Have a history of a major organ transplant (eg, heart, lung, kidney, liver) or
             hematopoietic stem cell/marrow transplant.

          -  Have a historically positive test or test positive at screening for HIV-1, hepatitis B
             surface antigen or hepatitis C antibody.

          -  Have an IgG Grade 3 or greater deficiency (less than or = to 400mg/dL).

          -  Have an IgA deficiency (IgA less than 10mg/dL).

          -  Have a history of an anaphylactic reaction to parenteral administration of contrast
             agents, human or murine proteins or monoclonal antibodies.

          -  Has a progressive medical, neurological or psychological condition or situation that,
             in the investigator's judgment, is likely to cause the subject to be unable or
             unwilling to participate in study procedures, to complete all scheduled assessments,
             or precludes accurate assessments.

          -  Is currently abusing drugs or alcohol or has history of abuse in the last 12 months.

          -  Subjects who have evidence of serious suicide risk including any history of suicidal
             behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the
             C-SSRS in the last 2 months or who in the investigator's judgment, pose a significant
             suicide risk.