Long-Acting Tacrolimus for the Treatment of Resistant Lupus Nephritis

Glomerulonephritis is one of the major disease manifestations of systemic lupus erythematosus (SLE). Around one-third of the patients, however, do not respond to conventional immunosuppressive therapy, and they have a high risk of progressing to dialysis-dependent renal failure. Recent studies suggest that immunosuppressive therapy targeted against the calcineurin pathway of T-helper cell, for example, tacrolimus, may be effective in the treatment of primary glomerulonephritis. The investigators plan to an open-label single-arm study the efficacy and safety of long-acting tacrolimus in the treatment of treatment-resistant lupus nephritis. Twenty-five patients with biopsy-proven lupus nephritis will be recruited. They will be treated with oral prednisolone and long-acting tacrolimus for 6 months, followed by 6 months of maintenance steroid and azathioprine. Proteinuria, renal function, clinical and serologic lupus activity will be monitored. This study will explore the potential role of long-acting tacrolimus in resistant lupus nephritis, which has a poor prognosis and no effective treatment at the moment.

Study Overview

• Status: Completed
• Conditions: Lupus Nephritis
• Intervention / Treatment: Drug: Long-acting tacrolimus (Advagraf, Astellas Pharma)

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 4

Contacts and Locations

Study Locations

• Hong Kong
  • Shatin, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age over 18 with informed consent.
• Fulfill the revised American College of Rheumatology criteria for SLE
• Biopsy-proven class III, IV, or V lupus nephritis within the past 24 months.
• Could not achieve complete remission after at least 4 months of conventional therapy (oral steroid plus cyclosphosphamide or mycophenolate mofetil).
• NB. Complete response is defined as proteinuria less than 0.5 g/day, with normal urinary sediment, a normal serum albumin concentration, and serum creatinine <15% above the base-line value.
• Female patients of child-bearing age and male patients agree to maintain effective birth control practice during the study.

Exclusion Criteria:

• Abnormal liver function tests
• Hepatitis B surface antigen or hepatitis C antibody positive
• Diabetic
• Receiving NSAID or other agents known to influence urinary
• Protein excretion
• Allergic or intolerant to macrolide antibiotics or tacrolimus

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: advagraf; Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months.	Drug: Long-acting tacrolimus (Advagraf, Astellas Pharma); Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall clinical response	complete response is defined as urinary protein < 0.5 g/day, with normal urinary sediment, normal serum albumin, and serum creatinine < 15% above the base-line value. Partial response is defined as urinary protein between 0.6 and 2.9 g/day, with a serum albumin > 30 g/dL, and stable renal function. No response is defined as urinary protein > 3 g/day or a value of 0.6 to 2.9 g/day but serum albumin < 30 g/dL, an increase in serum creatinine ≥ 50 µmol/l or 15% above the base-line value, or the discontinuation of treatment due to side effects.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
change in SLEDAI score	6 months
24-hour urinary protein excretion	6 months
renal function	6 months
development of lupus flare (renal or non-renal)	6 months

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: September 21, 2010
• First Submitted That Met QC Criteria: September 21, 2010
• First Posted (Estimate): September 22, 2010

Study Record Updates

• Last Update Posted (Estimate): December 4, 2012
• Last Update Submitted That Met QC Criteria: December 3, 2012
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Keywords: systemic lupus erythematosus; glomerulonephritis
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Kidney Diseases; Urologic Diseases; Connective Tissue Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Lupus Nephritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Calcineurin Inhibitors; Tacrolimus
• Other Study ID Numbers: AFKLN