Idiopathic Membranous Nephropathy (IMN) MedDRA version: 16.0 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857
Conditions
Interventions
Trade Name: BENLYSTA®
Product Name: BENLYSTA®
Product Code: GSK1550188 (Belimumab)
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: BELIMUMAB
CAS Number: 3565
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: 1. Age & Gender: Male or female between 18 and 75 years of age inclusive, at the time of signing the informed consent. 2. 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 (see inclusion 3), a biopsy should be available within the preceding 7 years. 3. Proteinuria: Have clinically active disease (nephrotic range proteinuria) for at least 3 months prior to screening and no improvement (400mg/mmol by uPCR (equates to >4.0g per 24 h) as measured from a 24 h 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 40 MlU/mL and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. 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-versushost- disease, Guillain-Barre syndrome. Infectious or parasitic diseases: Hepatitis B; Hepatitis C, syphilis, filariasis, hydatid disease, schistosomiasis, malaria, leprosy. Drugs and toxins: Gold, penicillamine, non-steroidal anti-inflammatory agents, mercury, captopril, formaldehyde, hydrocarbons, bucillamine. Miscellaneous: Tumors (excluded with reasonable diligence), renal transplantation, sarcoidosis, sickle cell disease, Kimura disease, angiofollicular lymph node hyperplasia. 2. Anti-PLA2R autoantibody: Patients known to be negative for anti-PLA2R autoantibody. 3. Severely reduced or deteriorating kidney function: An eGFR at screening 15% decrease in eGFR in 3 months before screening unless due to medication change). 4. Blood Pressure: Uncontrolled hypertension defined as blood pressure (BP) > 150/90 mm Hg (treatment target = 140/80) as assessed by either: a. Blood pressures measured 3 times on each of at least 2 clinic visits during screening, after the patient has sat quietly for at least 5 minutes, with >50% of measurements being >150/90 or b. Average daytime blood pressure on a 24 hour ambulatory blood pressure monitor. 5. Prior Therapy: Have received treatment with the following therapies at the times specified prior to Day 0:(please see protocol page 42 for further information) 6. Transplantation: Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. 7. 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. 8. Acute or chronic infection: Have required management of acute or chronic infections, please view section 5.2.2 of the protocol for further information. 9. 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). 10. 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. Please view section 5.2.2 of the protocol for further information. 11. 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 please view section 5.2.2 of the protocol for further information. 12. Liver function tests: Aspartate aminotransferase (AST) and alanine aminotransferas
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of 10mg/kg belimumab for the treatment of IMN as measured by remission of proteinuria at 2 years.;Secondary Objective: • To evaluate the safety and tolerability of belimumab 10mg/kg over a 2 year period in IMN. • To evaluate efficacy through other measures of disease activity over a 2 year period. • To evaluate the pharmacokinetics of belimumab in IMN over a 2 year period. • To evaluate the effect of belimumab on pharmacodynamic markers and other markers of autoimmunity and their relationship with clinical efficacy in IMN over a 2 year period. • To evaluate the effect of belimumb on quality of life in IMN over a 2 year period. • To evaluate the benefit of earlier treatment with belimumab compared to delayed treatment with current immunosuppressive treatment regimens during 2 years in the treatment period of the main clinical study and whether there is a positive effect following 2 years treatment in a 5 year off investigational drug follow-up period.;Primary end point(s): Incidence of remission (complete or partial) at Week 104 (complete remission [CR] is defined as uPCR 50% from baseline (Day 0) based on uPCR, together with no worsening of renal function [less than 15% reduction in eGFR from baseline]).;Timepoint(s) of evaluation of this end point: Week 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of progression of IMN or failure to respond as defined by: 1. Persistent symptomatic nephrotic syndrome potentially necessitating rescue therapy due to: • Persistent nephrotic range proteinuria with 30% increase from baseline) at any time OR • Symptoms or other clinically significant evidence of severe nephrotic syndrome- i.e. morbid oedema (defined as oedema that is distressing to a patient because of prolonged duration and inability to achieve adequate control with loop diuretics) or subclinical evidence of thromboembolism, severe hypoalbuminaemia (reduction by 5g/L from baseline and 20% OR • Persistent severe hypogammaglobulinaemia, 6 months. 2. ESRD (eGFR 350mg/mmol (proteinuria > 3.5g/24 hrs) AND increase of 50% from lowest remission level, in those patients who had previously achieved any type of remission) • Time to relapse (starting from time of first achievement of any type of remission) • Change from baseline in eGFR • Incidence of >20% decrease in eGFR at any time • Change from baseline in serum creatinine levels • Incidence of >50% increase in serum creatinine any time • Change from baseline in serum albumin levels • Change from baseline in cholesterol levels • Incidence of oedema by severity • Change from baseline in KDQOL-36 questionnaire score by visit • Change from baseline in Membranous Nephropathy Quality of Life (MN QOL) questionnaire score by visit • Change from baseline in Workplace Productivity and Activity Impairment (WPAI) questionnaire score by visit • Change from baseline in 6 minute walk test (6MWT) • Unscheduled healthcare contacts/resource utilisation • Requirement for rescue therapy • Change from baseline in anti-PLA2R antibody levels • Incidence of anti-PLA2R antibody remission. • Full response: Antibody undetectable • Partial response: Reduction in titres by 50% • Time to anti-PLA2R antibody remission • Serum belimumab C(0-30min), Cmin, AUC(0-tau), and urine Ae(0-24) • | — |
Countries
Australia, Canada, Czech Republic, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed