A 2 year study to investigate belimumab in membranous nephropathy

Phase 1

Conditions: Idiopathic Membranous Nephropathy (IMN)
MedDRA version: 15.0 Level: LLT Classification code 10027170 Term: Membranous nephropathy System Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Registration Number: EUCTR2011-000242-38-GB

Lead Sponsor: GlaxoSmithKline Research & Development Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 0

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 new 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 should be available for independent evaluation).
3. 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 >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.
4. 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 < 40 pg/mL (<147 pmol/L) is confirmatory]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods in Section 8.1 if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow
confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.
b. Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 74
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Non-Idiopathic MN 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 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 < 40 mL/min/1.73m2 (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).
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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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