Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy

Sponsor
Hospital Universitario 12 de Octubre
Study ID
NCT01955187
Phase
PHASE3
Status
Completed

Conditions

  • MEMBRANOUS NEPHROPATHY

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • TACROLIMUS — DRUG
    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.
  • RITUXIMAB — DRUG
    A dose 1 g IV will be given during month 6 (at day 180), before the onset of tacrolimus dose reduction
  • METHYLPREDNISOLONE — DRUG
    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.
  • CYCLOPHOSPHAMIDE — DRUG
    Month 2: Oral Cyclophosphamide (2.0 mg/kg/day) for 30 days. Months 4, and 6: Repeat month 2.

Study Details

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.

Key Dates

Start date
Jan 31, 2014
Status verified
Jan 2020
Primary completion
Jun 26, 2019
Completion
Jun 26, 2019

Study Design

Enrollment
86 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Sequential therapy: Tacrolimus-Rituximab
    Tacrolimus: Initial dose of 0.05 mg/Kg/day PO, adjusted to blood levels (5- 7 ng/ml) for six months. Starting at the end of month 6, tacrolimus will be reduced by 25% per month, resulting in a complete withdrawal at the end of month 9.
  • Active Comparator: Cyclical therapy: Corticosteroids and Cyclophosphamide
    Month 1, 3 and 5: 1g IV methylprednisolone daily for three doses, oral methylprednisolone (0.5mg/kg/day) Month 2, 4 and 6: Oral Cyclophosphamide (2.0 mg/kg/day)

Primary Outcome Measure

Proportion of patients with complete and/or partial remission. [ Time Frame: 24 months ]

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