Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy

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.

Conditions

• MEMBRANOUS NEPHROPATHY

Interventions

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.

Sponsors & Collaborators

• Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz

  collaborator OTHER

• Hospital Universitario Fundación Alcorcón

  collaborator OTHER

• Fundación para la Investigación Biomédica Hospital Universitario 12 de Octubre

  collaborator UNKNOWN

• Biobanco REDinREN

  collaborator UNKNOWN

• ERA-EDTA

  collaborator UNKNOWN

• REDinREN

  collaborator UNKNOWN

• Spanish Society of Nephrology

  collaborator OTHER

• Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

  collaborator OTHER

• University Hospital, Aachen

  collaborator OTHER

• Hospital Universitario 12 de Octubre

  lead OTHER

Principal Investigators

• GEMA FERNÁNDEZ-JUÁREZ, MD · Hospital Universitario Fundación Alcorcón, Madrid. Spain

• JESUS EGIDO, MD, PhD · IIS Fundación Jiménez Díaz, Madrid. Spain

• MARIAN GOICOCHEA, MD · Hospital Universitario Gregorio Marañón, Madrid. Spain

• ALFONS SEGARRA, MD, PhD · Hospital Universitari Vall d´Hebron, Barcelona. Spain

• GUILLERMO MARTÍN, MD · Hospital Regional de Málaga, Spain

• ILDEFONSO VALERA, MD · Hospital Virgen de la Victoria de Málaga. Spain

• VIRGINIA CABELLO, MD · Hospital Virgen del Rocío, Sevilla. Spain

• QUINTANA LUIS, MD · Hospital Clinic de Barcelona. Spain

• CAO MERCEDES, MD · Hospital Universitario de A Coruña. Spain

• AVILA ANA, MD · Hospital Dr. Peset, Valencia. Spain

• ESPINOSA MARIO, MD · Hospital Reina Sofía, Córdoba. Spain

• MONTSERRAT DIAZ, MD · Fundación Puigvert, Barcelona. Spain

• BONET JOSÉ, MD · Hospital Germans Trias i Pujol, Barcelona. Spain

• JUAN RAMÓN GÓMEZ-MARTINO, MD · Hospital San Pedro de Alcántara, Cáceres. Spain

• RIVAS BEGOÑA, MD · Hospital Universitario La Paz

• RODRIGUEZ ANTOLINA, MD · Hospital Clínico San Carlos, Madrid. Spain

• GALEANO CRISTINA, MD · Hospital Universitario Ramón y Cajal, Madrid. Spain

• RIVERA FRANCISCO, MD · Hospital de Ciudad Real. Spain

• WETZELS JACK, MD · Radboud University Medical Center

• JORGE ROJAS, MD · IIS Fundación Jiménez Díaz, Madrid. Spain

• MARUJA NAVARRO, MD · Hospital Germans Trias i Pujol, Barcelona. Spain

• ANA ROMERA, MD · Hospital de Ciudad Real. Spain

• IRENE AGRAZ, MD · Hospital Universitari Vall d´Hebron, Barcelona. Spain

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2019-06-26

Completion

2019-06-26

Countries

• Spain

Study Locations