Efficacy and Safety Study of Intravenous Belimumab Versus Placebo in Subjects With Idiopathic Membranous Nephropathy

Inclusion Criteria:

- Age & Gender: Male or female between 18 and 75 years of age inclusive, at the time of
signing the informed consent.

- Histological diagnosis: Have clinical diagnosis of IMN, as verified by biopsy (either
by light microscope with immuno-fluorescence, or by electron microscope) in the last
3 years (biopsy results [and slides where possible] should be available for
independent evaluation). For patients with relapsed disease, a biopsy should be
available within the preceding 7 years.

- Proteinuria: Have clinically active disease (nephrotic range proteinuria) for at
least 3 months prior to screening and no improvement (<30% reduction), despite
supportive therapy (which must include maximal tolerated doses of ACE inhibitor or
ARB unless contraindicated, and may include statins, diuretics, dietary salt
restriction). During screening proteinuria must be >400 mg/mmol by uPCR (or >4.0 g
per 24 hrs) as measured from a 24 hrs urine collection and/or spot urine sample
(early morning where possible) on 2 occasions at least 7 days apart.

- Proteinuria in patients with relapsed disease: Patients who previously achieved
proteinuria <2 g per 24h for at least 6 months and have subsequently relapsed with
proteinuria levels as documented above, may be eligible providing recurrence has been
within the previous 3 years and patient is known to be anti-PLA2R positive.

- Female Subject is eligible to participate if she is not pregnant or nursing; is
non-childbearing potential. Females of child-bearing potential must agree to use one
of the approved contraception methods for an appropriate period of time (as
determined by the product label or investigator) prior to the start of dosing to
sufficiently minimise the risk of pregnancy at that point. Female subjects must agree
to use contraception until 16 weeks after the last dose.

- French subjects: In France, a subject will be eligible for inclusion in this study
only if either affiliated to or a beneficiary of a social security category.

- Inclusion Criteria for Long Term Follow-up: Subjects who have signed informed consent
for the Long Term Follow-up and have completed 2 years study treatment and the 16
week follow-up visit, or who have withdrawn early from study treatment but completed
the Week 104 Withdrawn visit.

Exclusion Criteria:

- Non-Idiopathic MN or other condition affecting the kidney: If the diagnosis of MN is
secondary to other conditions, or the subject has renal impairment from a condition
that is not MN. Causes of secondary MN include (but are not limited to) Immune
diseases (Systemic lupus erythematosus, diabetes mellitus; rheumatoid arthritis,
Hashimoto's disease, Grave's disease, mixed connective tissue disease, Sjogren's
syndrome, primary biliary cirrhosis, bullous pemphigoid, small bowel enteropathy
syndrome, dermatitis herpetiformis, ankylosing spondylitis,
graft-versus-host-disease, Guillain-Barre syndrome); or Infectious or parasitic
diseases (Hepatitis B; Hepatitis C, syphilis, filariasis, hydatid disease,
schistosomiasis, malaria, leprosy); or Drugs and toxins (Gold, penicillamine,
non-steroidal anti-inflammatory agents, mercury, captopril, formaldehyde,
hydrocarbons, bucillamine); or Miscellaneous(Tumors excluded with reasonable
diligence, renal transplantation, sarcoidosis, sickle cell disease, Kimura disease,
angiofollicular lymph node hyperplasia).

- Anti-PLA2R autoantibody: Patients known to be negative for anti-PLA2R autoantibody.

- Severely reduced or deteriorating kidney function: An eGFR at screening <40
mL/min/1.73m^2 (as determined by 4 variable version MDRD equation) or kidney function
not stable (as defined by >15% decrease in eGFR in 3 months before screening unless
due to medication change).

- Blood Pressure: Uncontrolled hypertension defined as blood pressure (BP) >150/90 mmHg
(treatment target <=140/80)

- Prior Therapy: Have received treatment with the following therapies at the times
specified prior to Day 0: Therapy - B-cell targeted therapy except rituximab (e.g.,
other anti- CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab],
BLyS-receptor fusion protein [BR3], TACI Fc, or belimumab), Time period: anytime;
Therapy: Rituximab (subjects with rituximab treatment between 1 and 2 years prior to
Day 0 are eligible if there is documented evidence of B-cell repopulation to >50% of
pre-treatment levels), Period: 2 years; Therapy: Abatacept and any other biologic
investigational agent other than B cell targeted therapy (i.e. not approved for sale
in the country in which it is being used), Time Period: 364 days; Therapy:
Cyclophosphamide or chlorambucil 3 or more courses of systemic corticosteroids for
concomitant conditions (e.g., asthma, atopic dermatitis). (Topical or inhaled
steroids are permitted.), Time Period: 180 days; Therapy: Anti-tumour necrosis factor
(TNF) or anti-IL-6 therapy (e.g. adalimumab, etanercept, infliximab, tocilizumab).
Interleukin-1 receptor antagonists (e.g. anakinra). Other
immunosuppressive/immunomodulatory agents (e.g azathioprine, 6-mercaptopurine,
mycophenolate mofetil (PO)/ mycophenolate mofetil hydrochloride (IV), mycophenolate
sodium (PO), methotrexate, tacrolimus, sirolimus, thalidomide, leflunomide,
mizoribine, ciclosporin). Intravenous immunoglobulin (IVIG). Plasmapheresis,
leukapheresis, Time Period: 90 days; Therapy: A non-biologic investigational agent
(i.e. not approved for sale in the country in which it is being used). Intravenous
corticosteroid, Adrenocorticotropic hormone (ACTH). Aliskiren. A change in dose of
>50% for angiotensin pathway antihypertensive (e.g., ACE inhibitor, angiotensin
receptor blocker), Time Period: 60 days; Therapy: A live vaccine. Greater than
30mg/day corticosteroid, Time Period: 30 days; Therapy: Greater than 10mg/day
corticosteroid. A change in dose of a corticosteroid. Note: Changes to inhaled
steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams)
are allowed, Time Period: 14 days.

- Transplantation: Have a history of a major organ transplant (e.g., heart, lung,
kidney, liver) or hematopoietic stem cell/marrow transplant.

- Cancer: 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.

- Acute or chronic infection: Have required management of acute or chronic infections
such as currently on any suppressive therapy for a chronic infection such as
tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and
atypical mycobacteria); or hospitalisation for treatment of infection within 60 days
prior to Day 0; or use of parenteral (IV or IM) antibiotics (anti-bacterials,
anti-virals, anti-fungals, or anti-parasitic agents) within 60 days prior to Day 0.

- Liver disease: Current or chronic history of liver disease, or known hepatic or
biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic
gallstones).

- Other diseases/conditions: Have clinical evidence of significant unstable or
uncontrolled acute or chronic diseases not due to IMN (i.e., cardiovascular,
pulmonary, haematologic, gastrointestinal, hepatic, renal, neurological, malignancy
or infectious diseases) which, in the opinion of the investigator, could confound the
results of the study or put the subject at undue risk; or have a planned surgical
procedure or a history of any other medical disease (e.g. cardiopulmonary),
laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion
of the investigator, makes the subject unsuitable for the study.

- Positive serology: Have a historically positive HIV test or test positive at
screening for HIV. Serologic evidence of Hepatitis B (HB) infection based on the
results of testing for HBsAg, anti-HBc and anti-HBs. Positive test for Hepatitis C
antibody confirmed on the same sample with a Hepatitis C RIBA immunoblot assay if
available.

- Liver function tests: Aspartate aminotransferase (AST) and alanine aminotransferase
(ALT) >=2x upper limit of normal (ULN); alkaline phosphatase and bilirubin >1.5xULN
(isolated bilirubin >1.5ULN is acceptable if bilirubin is fractionated and direct
bilirubin <35%).

- Immunodeficiency: Have an IgA deficiency (IgA level < 10 mg/dL) or have IgG level
<250 mg/dL and have previously received any non-glucocorticoid immunosuppression
during the previous 6 months.

- Laboratory test abnormalities: Have clinically significant abnormalities in screening
laboratory assessments (not related to the disease), as judged by investigator.

- Drug sensitivity / Anaphylaxis: History of sensitivity or intolerance 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. History of an anaphylactic reaction to parenteral administration of
contrast agents, human or murine proteins or monoclonal antibodies.

- Suicidality: Subjects who have evidence of serious suicide risk including any history
of suicidal behaviour in the last 6 months and/or any suicide ideation of type 4 or 5
on the Columbia Suicide-Severity Rating Scale (C-SSRS) in the last 2 months or who in
the investigator's judgement, pose a significant suicide risk.

- Substance abuse: Evidence of current drug or alcohol abuse or dependence.

- Blood donation: Where participation in the study would result in donation of blood or
blood products in excess of 500 mL within a 56 day period.