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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00302549
• Other study ID #: NJCT-0602
• Status: Completed
• Phase: N/A
• First received: March 13, 2006
• Last updated: May 25, 2010
• Start date: May 2004
• Est. completion date: February 2006

Study information

• Verified date: July 2008
• Source: Nanjing University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: February 2006
• Est. primary completion date: May 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Female patients with a diagnosis of Systemic Lupus Erythematosus (SLE) according to the criteria of American Rheumatic Association, 1982 (Appendix 1) aged between 18-65 years, and whose score of SLE-DAI (Disease Active Index, Appendix 2) is greater than 10.

2. Patients diagnosed to have class III or IV LN by renal biopsy, according to the WHO classification criteria (1995, Appendix 3) within 3 month and have significant active pathological lesion.

3. Patients with a proteinuria = 2g/24h, and an active urine sediment (Hematuria with white cells and casts in urine).

4. Patients who signed written informed consent form (patients less than 18 years old with their parents/legal representative's signatures), and have given their consent to follow all study procedures and follow-up.

Exclusion Criteria:

1. Patients who have received treatment of cytotoxic drugs such as CTX, Mycophenolate mofetil (MMF) cyclosporine for more than 1 week within three months, but Azathioprine (AZa) are accepted.

2. Patients with serum creatinine > 3 mg/dl(265µmol/L).

3. Patients with severe infection or central nervous system symptoms.

4. Patients who have impaired liver function, with ALT/GPT or AST/GOT twice more than the normal upper limit or who have active hepatitis.

5. Patients who have abnormal glucose, with a fasted blood glucose > 6.2 mmol/L or post meal blood glucose > 11.2 mmol/L.

6. Patients who are pregnant or lactating.

7. Patients who are known to be allergic to a macrolide.

8. Patients who use Erythromycin, Fluconazole, Ethinylestradiol, Rifampicin, and Carbamazepine.

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

Intervention

Drug:
• FK506
FK506,0.1mg/kg/d

Locations

Country	Name	City	State
China	Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine	Nanjing	Jiangsu

Sponsors (2)

Lead Sponsor	Collaborator
Nanjing University School of Medicine	Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To compare the efficacy of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN		6 months	Yes
Secondary	To compare the safety and tolerability of FK506 vs intravenous cyclophosphamide pulses in the treatment of class III-IV LN and to explore the dosing of FK506 and its effective range of blood concentration.		6 months	Yes