A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome

Asahi Kasei Medical

Status and phase: Completed; Phase 3

Conditions: Nephrotic Syndrome

Treatments: Drug: Mizoribine (MZR); Drug: Cyclophosphamide (CTX)

Study type: Interventional

Funder types: Industry

Identifiers

NCT02257697

HE-69-C-Ne-302

Details and patient eligibility

About

To demonstrate that the treatment effect in refractory nephrotic syndrome of MZR is non-inferior to that of standard therapy CTX through analyzing overall remission rate after treatment.

Enrollment: 239 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients who have medical history with clear documentation of diagnosis of nephrotic syndrome
• Patient who received renal biopsy within 1 year prior to screening and confirmed the pathologic classification: Minimal Change Disease (MCD), IgA nephropathy, Mesangioproliferative Glomerulonephritis (MsPGN), Membranous Nephropathy (MN), Focal Segmental Glomerulosclerosis (FSGS)
• Patient with the above different pathologic classification who received adequate hormone therapy more than 8 weeks (including FSGS more than 12 weeks)prior to screening and have 24hr-urine protein≥2.0g/day at screening Adequate hormone dose is defined as prednisone (prednisolone) equivalent dose of 0.8 to 1.0 mg/kg/day (inclusive)
• Male or female patient between 18 and 70 years (inclusive) at informed consent obtained date
• Patient with body weight between 40kg and 80kg (inclusive) at screening
• Patients who sign the informed consent form

Exclusion criteria

• Other primary nephrotic syndrome, e.g. membrano-proliferative glomerulonephritis (MPGN)
• Secondary nephrotic syndrome (e.g. diabetic nephropathy, anaphylactic purpura nephritis, lupus nephritis, type B hepatitis-related nephritis, renal amyloidosis)
• Patient who had history of allergy to any investigational product (MZR, CTX) or hormone
• Patient who had received accumulated dosage of CTX >3g within one year prior to screening
• Patient who had received immunosuppressant or Chinese traditional medicine with immunosuppressive effect within 30 days prior to screening
• Patient who received other investigational drugs within 30 days prior to screening
• Patient who have received plasma exchange therapy or immunoadsorption therapy within 30 days prior to screening
• Patient who require pentostatin or live vaccine (not including flu vaccine)
• Patient who is undergoing renal replacement therapy
• Patient who received kidney transplantation
• Patient with malignancy
• Patient with severe hypertension (SBP > 160mmHg or DBP > 100mmHg) which has not been effectively controlled
• Patient with white blood cell count <3×109/L /L(=3.0 GI/L)
• Patient with SCr > 176.8μmol/L
• Patient who has a value that is > 3 times of the upper limit of normal range for AST or ALT
• Patient with hepatitis B, hepatitis C or HIV infection
• Patient with other serious infections
• Patient who is unsuitable for participating in this study in the opinion of investigators ( e.g. uncontrolled diabetes, central nervous system lupus , lupus encephalopathy, active psychosis,osteonecrosis of the femoral head, fulminant hepatitis, peptic ulcer, etc.)
• Female patient who is pregnant, currently breast feeding or willing to become pregnant
• Patient with any other diseases that would affect the evaluation of efficacy or safety

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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239 participants in 2 patient groups

Mizoribine (MZR)

Experimental group

Description:

Oral administration, daily dose of 150mg (50mg/tablet, t.i.d) All study subjects will receive standard steroid therapies during the study.

Treatment:

Drug: Mizoribine (MZR)

Cyclophosphamide (CTX)

Active Comparator group

Description:

Intravenous injection with between 0.5 to 1.0 g/m2 body surface area each time (the maximum dose is 1.0 g/day each time). All study subjects will receive standard steroid therapies during the study.

Treatment:

Drug: Cyclophosphamide (CTX)