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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01762852




Registration number
NCT01762852
Ethics application status
Date submitted
4/01/2013
Date registered
8/01/2013
Date last updated
22/03/2017

Titles & IDs
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
Secondary ID [1] 0 0
114674
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glomerulonephritis, Membranous 0 0
Condition category
Condition code
Renal and Urogenital 0 0 0 0
Kidney disease
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Belimumab 10 mg
Treatment: Drugs - Placebo

Experimental: Belimumab Arm - Subjects will receive belimumab 10 mg/kg intravenous infusion \[will last for 1 hour (hr)\] on Day 0, Week 2, Week 4, then every 4 weeks for up to 100 weeks with frequency adjusted for subjects with \>1000 mg/mmol uPCR (\>10 g/24 hrs). All subjects will receive background supportive therapy throughout the study.

Placebo comparator: Placebo Arm - Intravenous infusion (will last for 1 hr) on Day 0, Week 2, Week 4, then every 4 weeks for up to 100 weeks with frequency adjusted for subjects with \>1000 mg/mmol uPCR (\>10 g/24 hrs). All subjects will receive background supportive therapy throughout the study.


Treatment: Drugs: Belimumab 10 mg
Belimumab is Lyophilised powder for reconstitution in 4.8 mL sterile water for injection (SWFI) and diluted in normal saline (250 mL). 400 mg per vial plus excipients (citric acid/sodium citrate/sucrose/polysorbate). Belimumab 10 mg/kg intravenous infusion (will last for 1 hr) on Day 0, Week 2, Week 4, then every 4 weeks for up to 100 weeks

Treatment: Drugs: Placebo
Normal saline solution (sodium chloride 154 mmol/L). Intravenous infusion (will last for 1 hr) on Day 0, Week 2, Week 4, then every 4 weeks for up to 100 weeks

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of remission (complete [CR] or partial [PR]) at Week (WK) 104
Timepoint [1] 0 0
104 weeks
Secondary outcome [1] 0 0
Incidence of progression of IMN or failure to respond
Timepoint [1] 0 0
Upto Week 104
Secondary outcome [2] 0 0
Time to complete remission
Timepoint [2] 0 0
Up to Week 104
Secondary outcome [3] 0 0
Time to partial remission
Timepoint [3] 0 0
Up to Week 104
Secondary outcome [4] 0 0
Change from baseline in proteinuria levels at Week 104
Timepoint [4] 0 0
Week 0 and Week 104
Secondary outcome [5] 0 0
Change from baseline in serum albumin levels at Week 104
Timepoint [5] 0 0
Week 0 and Week 104
Secondary outcome [6] 0 0
Change from baseline in eGFR at Week 104
Timepoint [6] 0 0
Week 0 and Week 104
Secondary outcome [7] 0 0
Time to first thromboembolic event
Timepoint [7] 0 0
Up to Week 104
Secondary outcome [8] 0 0
Change from baseline in KDQOL-36 score at Week 104
Timepoint [8] 0 0
Week 0 and Week 104
Secondary outcome [9] 0 0
Incidence of partial remission at Week 104
Timepoint [9] 0 0
Week 104
Secondary outcome [10] 0 0
Incidence of complete remission at Week 104
Timepoint [10] 0 0
Week 104
Secondary outcome [11] 0 0
Duration of remission (complete or partial)
Timepoint [11] 0 0
Up to Week 104
Secondary outcome [12] 0 0
Risk-benefit calculation based on key efficacy and safety endpoints using a clinical utility index
Timepoint [12] 0 0
Up to Week 104
Secondary outcome [13] 0 0
Incidence of serious adverse events (SAEs)
Timepoint [13] 0 0
Up to Week 104
Secondary outcome [14] 0 0
Incidence of adverse events (AEs) of special interest
Timepoint [14] 0 0
Up to Week 104
Secondary outcome [15] 0 0
Safety assessed by evaluation of Adverse events, clinical laboratory assessments, vital signs and immunogenicity
Timepoint [15] 0 0
Up to 116 Weeks
Secondary outcome [16] 0 0
Survival without renal progression
Timepoint [16] 0 0
From start of treatment up to 7 years

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - New Lambton
Recruitment postcode(s) [1] 0 0
2305 - New Lambton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Missouri
Country [2] 0 0
United States of America
State/province [2] 0 0
North Carolina
Country [3] 0 0
Canada
State/province [3] 0 0
Alberta
Country [4] 0 0
Canada
State/province [4] 0 0
Ontario
Country [5] 0 0
Czech Republic
State/province [5] 0 0
Praha 2
Country [6] 0 0
France
State/province [6] 0 0
Amiens cedex 1
Country [7] 0 0
France
State/province [7] 0 0
Créteil Cedex
Country [8] 0 0
France
State/province [8] 0 0
Paris Cedex 15
Country [9] 0 0
France
State/province [9] 0 0
Toulouse Cedex 9
Country [10] 0 0
Germany
State/province [10] 0 0
Baden-Wuerttemberg
Country [11] 0 0
Germany
State/province [11] 0 0
Bayern
Country [12] 0 0
Germany
State/province [12] 0 0
Nordrhein-Westfalen
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Italy
State/province [14] 0 0
Lombardia
Country [15] 0 0
Italy
State/province [15] 0 0
Toscana
Country [16] 0 0
Netherlands
State/province [16] 0 0
Amsterdam
Country [17] 0 0
Netherlands
State/province [17] 0 0
Nijmegen
Country [18] 0 0
Spain
State/province [18] 0 0
L'Hospitalet de Llobregat
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Cardiff
Country [22] 0 0
United Kingdom
State/province [22] 0 0
Gloucester
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Leicester
Country [24] 0 0
United Kingdom
State/province [24] 0 0
London
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Reading

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.