Idiopathic Membranous Glomerulonephropathy (IMGN) MedDRA version: 16.1 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 100000004857
Conditions
Interventions
Trade Name: BENLYSTA® (belimumab)
Product Name: Benlysta (belimumab)
Product Code: GSK1550188
Pharmaceutical Form: Powder for solution for infusion
Sponsors
GlaxoSmithKline Research and 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 IMGN, as verified by biopsy (either by light microscope with immuno-fluorescence, or by electron microscope) in the last 7 years with non-active disease >3 years (non-active defined as subject not on immunosuppressants and proteinuria 400mg/mmol by PCR (or >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. 5. Female Subjects: A female subject is eligible to participate if she is not pregnant or nursing and at least one of the following conditions apply: a. Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply: 1. Non-Idiopathic MGN or other condition affecting the kidney: If the diagnosis of MGN is secondary to other conditions, or the subject has renal impairment from a condition that is not MGN. Causes of secondary MGN 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-Barré 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: Tumours (excluded with reasonable diligence), renal transplantation, sarcoidosis, sickle cell disease, Kimura disease, angiofollicular lymph node hyperplasia. 2.Severely reduced or deteriorating kidney function: An eGFR at screening 15% decrease in eGFR in 3 months before screening, unless due to medication change). 3. 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. 4. Prior Therapy: Have received treatment with the therapies (as per protocol page 39-see table) at the times specified prior to Day 0: Corticosteroid dose represents prednisolone or prednisolone equivalent. 5. Transplantation: Have history of a major organ transplant (e.g heart, lung, kidney,liver) or hematopoietic stem cell/marrow transplant. 6. 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. 7. Acute or chronic infection: Have required management of acute or chronic infections, as follows: • Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). • Hospitalisation for treatment of infection within 60 days prior to Day 0. • Use of parenteral (IV or IM) antibiotics (anti-bacterials, anti-virals, antifungals, or anti-parasitic agents) within 60 days prior to Day 0. 8. 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). 9. Other diseases/conditions: Have clinical evidence of signi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is: To evaluate whether belimumab can modulate proteinuria in IMGN. To evaluate whether belimumab can modulate anti-PLA2R autoantibodies in patients with detectable baseline levels of these antibodies. ; Secondary Objective: Secondary objectives: To evaluate the safety and tolerability of belimumab 10mg/kg over a 2 year period in IMGN. To assess the pharmacokinetics (PK) of belimumab 10mg/kg in patients with IMGN. To evaluate the effect of belimumab on pharmacodynamic (PD) markers and other markers of autoimmunity and their relationship with clinical measures in IMGN. To evaluate the effect of belimumab on quality of life in IMGN. ; Primary end point(s): • Change from baseline in proteinuria levels at week 28 • Change from baseline in anti-PLA2R autoantibody titres at week 28 ;Timepoint(s) of evaluation of this end point: week28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Weeks 12, 28, 52, 76 and 104 (dependent on endpoint); Secondary end point(s): • Change from baseline in proteinuria levels • Change from baseline in anti-PLA2R autoantibody titres • Change from baseline in urine levels of belimumab • Incidence of complete or partial remission -Complete remission: PCR 50% from Day 0 baseline, together with no worsening in renal function (eGFR reduction from baseline 350mg/mmol AND increase of 50% from lowest remission level, in those subjects who had previously achieved any type of remission) • Incidence of anti-PLA2R autoantibody remission: -Full response: Antibody undetectable -Partial response: Reduction in titres by 50% • Time to anti-PLA2R autoantibody remission • Incidence of anti-PLA2R autoantibody relapse (antibody detectable after previously undetectable) • Change from baseline in eGFR levels • Change from baseline in serum creatinine levels • Change from baseline in levels of serum albumin • Change from baseline in levels of cholesterol • Incidence of oedema (extending beyond calf) • Serum belimumab Cmax, Cmin, AUC(0-2), and urine Ae(0-24) • Change from baseline in SF-36 v2 Quality of Life (QoL) questionnaire score • Pharmacodynamic/biomarker endpoints may include Urine membrane attack complex (MAC), B Cell and T Cell sub-populations, BLyS levels, cytokines/chemokines (may include but not limited to IL-21, IL-17, IL-4, IL-10, IFN-Gamma), antigen specific lymphocyte response, autoantibody profile, change in transcriptomic profile or other markers of IMGN or autoimmune pathology, as data permit. • Safety and tolerability as assessed by evaluation of adverse events | — |
Countries
United Kingdom
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development
Outcome results
None listed