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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01762852
• Date of registration: 04/01/2013
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Efficacy and Safety Study of Intravenous Belimumab Versus Placebo in Subjects With Idiopathic Membranous Nephropathy
• Scientific title: BEL114674: A 2 Year Study of Efficacy and Safety of Intravenous Belimumab Versus Placebo in Subjects With Idiopathic Membranous Nephropathy
• Date of first enrolment: April 2013
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT01762852
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Australia, Canada, Czech Republic, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Glomerulonephritis, Membranous

Intervention(s)

Drug: Belimumab 10 mg

Drug: Placebo

Primary Outcome(s)

Incidence of remission (complete [CR] or partial [PR]) at Week (WK) 104 [Time Frame: 104 weeks]

Secondary Outcome(s)

Incidence of partial remission at Week 104 [Time Frame: Week 104]

Survival without renal progression [Time Frame: From start of treatment up to 7 years]

Change from baseline in eGFR at Week 104 [Time Frame: Week 0 and Week 104]

Incidence of progression of IMN or failure to respond [Time Frame: Upto Week 104]

Change from baseline in proteinuria levels at Week 104 [Time Frame: Week 0 and Week 104]

Change from baseline in serum albumin levels at Week 104 [Time Frame: Week 0 and Week 104]

Safety assessed by evaluation of Adverse events, clinical laboratory assessments, vital signs and immunogenicity [Time Frame: Up to 116 Weeks]

Duration of remission (complete or partial) [Time Frame: Up to Week 104]

Time to complete remission [Time Frame: Up to Week 104]

Time to first thromboembolic event [Time Frame: Up to Week 104]

Change from baseline in KDQOL-36 score at Week 104 [Time Frame: Week 0 and Week 104]

Incidence of adverse events (AEs) of special interest [Time Frame: Up to Week 104]

Incidence of complete remission at Week 104 [Time Frame: Week 104]

Incidence of serious adverse events (SAEs) [Time Frame: Up to Week 104]

Risk-benefit calculation based on key efficacy and safety endpoints using a clinical utility index [Time Frame: Up to Week 104]

Time to partial remission [Time Frame: Up to Week 104]

Secondary ID(s)

114674

Source(s) of Monetary Support

Please refer to primary and secondary sponsors