To Compare the Efficacy and Safety of FK506 vs IVC in the Treatment of Class III-IV LN

Lupus Nephritis Clinical Trial

Official title: To Compare the Efficacy and Safety of FK506 vs IVC in the Treatment of Class

Status Completed

Clinical Trial Summary

1. To compare the efficacy of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN.

2. To compare the safety and tolerability of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN.

3. To explore the dosing of FK506 and its effective range of blood concentration.

Clinical Trial Description

Corticosteroid combined with cytotoxic drugs has been regarded as the conventional therapy for Class IV Lupus Nephritis (LN), because of its efficacy in improving patients' long term survival. However, this treatment fails in some patients, especially those who present with significant vascular lesion. In addition, cyclophosphamide (CTX) has severe side effects with a high incidence of marrow inhibition and infection.FK506 (Tacrolimus) is a new calcineurin inhibitor. Similar to Cyclosporine (CsA), it inhibits the production of IL-2 and activation of T cells. Furthermore, it has an added value of inhibiting the production of IL-10 from Th2 cells, thus reducing the production of auto antibodies from B cells.It also exerts its specific immunosuppressive effects through CsA-insensitive pathway. FK506 could inhibit not only the activation of naive T cells but also the activation and proliferation of primed T cells.FK506 is 10 -100 times more powerful than CsA in inhibiting the activation of T cells.Animal studies on MRL/lpr mice LN model demonstrated that FK506 could significantly depress the excretion of urine protein and the level of serum anti-dsDNA, inhibit glomerular cellular proliferation and formation of crescents, and reduce the deposits of immune complex.

A preliminary study showed that FK506 was significantly effective on patients with IV LN,as indicated by rapid reduction of urine protein, increase in serum albumin, decrease in auto antibodies together with remission of lesion activity of the renal tissue. However, the drawbacks of this study were the small sample size and the lack of a controlled group. Hence, a multi-center controlled study comparing FK506 with cytotoxic agents to evaluate the efficacy and safety of FK506 on patients with III or IV LN, and explore the effective range of FK506 blood concentration and the appropriate target patient population would be needed. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Nephritis
• Nephritis

• NCT number: NCT00302549
• Study type: Interventional
• Source: Nanjing University School of Medicine
• Status: Completed
• Phase: N/A
• Start date: May 2004
• Completion date: February 2006