NCT01955187

Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy

European Multicenter and Open-Label Controlled Randomized Trial to Evaluate the Efficacy of Sequential Treatment With Tacrolimus-Rituximab Versus Steroids Plus Cyclophosphamide in Patients With Primary Membranous Nephropathy (The STARMEN Study)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 86 (actual)
• Sponsor: Hospital Universitario 12 de Octubre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

In this study, investigators will evaluated the long-term efficacy and safety (two years) of Tacrolimus-Rituximab (RTX) therapy compared to Methylprednisolone-Cyclophosphamide (CYC) therapy in patients with primary Membranous Nephropathy (MN). PRINCIPAL OBJECTIVE To evaluate whether sequential therapy with tacrolimus leads to a greater increase in the proportion of primary MN patients with Complete or Partial Remission when compared with patients receiving standard treatment. It will be assessed 24 months after the beginning of treatment. Phase of the trial: and design: Phase III study, open label, randomized, and active controlled trial. This study will have 3 stages: screening and recruitment of patients for 18 months, treatment period for six months in corticosteroids plus CYC group and 9 months in Tacrolimus-RTX group, and finally post-treatment follow-up period until to complete 24 months of follow-up since initial treatment. This study will compare the standard therapy for primary MN patients with nephrotic range proteinuria (active control of steroids plus CYC) with a novel sequential therapy of tacrolimus and RTX, an approach of potential high efficacy, low toxicity and more acceptable safety profile.

Detailed description

PRIMARY AND SECONDARY ENDPOINTS/OUTCOME MEASURES Primary end-point: The proportion of patients reaching CR defined as a reduction of proteinuria since baseline level to a value equal or lower than 0.5 g/24 h proteinuria plus stable renal function (eGFR ≥ 45 ml/min/1.73m2) or PR defined as a reduction of proteinuria since baseline level to a value less than 3.5 g/24 h and 50% lower than baseline proteinuria plus stable renal function (eGFR ≥ 45ml/min/1.73m2) at 24 months of study treatment. Secondary end-points * The proportion of patients with Limited response (LR) defined as a reduction of proteinuria since baseline level \> 50% but to a value \> 3.5g/24 h. at 12, 18 and 24 months of study treatment.. * The number of patients with an increase ≥ 50% of serum creatinine (SCr) from baseline at 12, 18 and 24 months (end of the follow-up). * The time of renal survival (status free of increase ≥ 50% of baseline SCr) in both arms overall after the study. * The proportion of patients with preserved renal function (estimated GFR ≥ 60 ml/min) in both treatment arms after the treatment period. * The proportion of patients with relapse (defines as the reappearance of proteinuria \> 3.5 gr/24h and at least 50% increase over the lowest baseline value in at least three consecutive visits in those patients who previously presented a PR or CR) and the time to relapse after the treatment period. * Serum levels of anti-phospholipase A2 receptor antibodies (anti-PLA2R), before of treatment and at 3, 6, 9, 12, 18 and 24 months of study, in both treatment arms. * The proportion of patient with drug-related adverse events and serious adverse events. STUDY POPULATION Patients with biopsy-proven idiopathic or primary membranous nephropathy with nephrotic proteinuria and normal or slight decrease of renal function will be enrolled.

Conditions

• MEMBRANOUS NEPHROPATHY

Interventions

Type	Name	Description
DRUG	TACROLIMUS	Initial dose: 0.05 mg/Kg/day, adjusted to achieve blood trough levels of 5-7 ng/ml) for six months. Starting at the end of month 6, tacrolimus dosage will be reduced by 25% per month, resulting in a complete withdrawal at the end of month 9.
DRUG	RITUXIMAB	A dose 1 g IV will be given during month 6 (at day 180), before the onset of tacrolimus dose reduction
DRUG	METHYLPREDNISOLONE	Month 1: 1g IV methylprednisolone daily for three doses (days 1, 2, and 3), Oral methylprednisolone (0.5mg/kg/day) for 27 days (days 4 to 30). Months 3, and 5: Repeat Month 1.
DRUG	CYCLOPHOSPHAMIDE	Month 2: Oral Cyclophosphamide (2.0 mg/kg/day) for 30 days. Months 4, and 6: Repeat month 2.

Timeline

• Start date: 2014-01-01
• Primary completion: 2019-06-26
• Completion: 2019-06-26
• First posted: 2013-10-07
• Last updated: 2020-01-18

Locations

1 site across 1 country: Spain