Sirolimus in Treatment of Proteinuric Flares of Lupus Nephritis

Peking Union Medical College Hospital20 enrolled

Overview

This a single-centre, one-arm, open-label pilot study. Eligible patients with mild proteinuric flares of lupus nephritis Class III/IV±V are received sirolimus without changing previous immunosuppressive medication during 12-week follow-up. Primary Objective: * To investigate the efficacy of sirolimus for mild proteinuric flares in patients with Class III/IV±V lupus nephritis Secondary Objective: * To assess the safety and tolerability of sirolimus treatment for mild proteinuric flares in patients with Class III/IV±V lupus nephritis

Lupus nephritis is a common and serious complication of systemic lupus erythematosus (SLE). It often requires aggressive immunosuppressive therapy. Although majority of patients with severe lupus nephritis achieve a complete or partial remission after 6-month induction treatment, renal flares can still occur during maintenance therapy. Whether patients with mild proteinuric flares should receive intensive immunosuppressive therapy is unclear. In pathogenesis of SLE, T-cell dysfunction is attributed to the activation of the mammalian target of rapamycin (mTOR). Previous prospective and retrospective studies in SLE or lupus nephritis showed the effect of mTOR blockade on systemic disease activity index or severe lupus nephritis as initial or maintenance therapy. Eligible subjects with biopsy-proven Class III/IV±V lupus nephritis(ISN/RPS 2003) are received oral sirolimus without change previous immunosuppressive therapy. We follow up the included patients at Week 2, Week 4, Week6, Week 8 and Week 12 regularly. The investigator will actively detect and inquire about the occurrence of adverse events (AEs)/ severe adverse events (SAEs) at every visit/ contact during the study. The clinical trials insurance is prepaid by sponsor to cover the design risks of the protocol and liability/ compensation to the research subject for bodily injury or death resulting from their participation in the trial.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Biopsy-proven Class III or IV±V lupus nephritis (ISN/RPS 2003 lupus nephritis classification) with biopsy performed within 48 weeks before inclusion. * Males or females aged 18 to 60 years old at the time of screening. * The mild proteinuric flare of lupus nephritis is defined as meeting all of the following criteria : 1. Persistently increased proteinuria after complete remission, and 24-hr proteinuria≥1.0g/day or doubling of proteinuria after partial remission, and 24-hr proteinuria≥2.0g/day 2. No hypoalbuminemia: serum albumin ≥35g/L 3. Stable renal function: serum creatinine\<25% increase above the level at the time of renal disease remission * Eligible to sign informed-consent independently Exclusion Criteria: * Renal disease unrelated to SLE (e.g. diabetes mellitus, other glomerular or tubulointerstitial diseases, renovascular disease), or transplanted kidney * Estimate glomerular filtration rate (eGFR by CKD-EPI)\<45mL/min per 1.73m\^2 at the time of screening * Renal biopsy showing cellular of fibrocellular crescent in more than 25% of glomeruli * Central nervous system (CNS) or other severe organ manifestations of lupus that necessitate aggressive immunosuppressive therapy on its own. * Co-morbidities that require corticosteroid therapy (e.g. asthma, inflammatory bowel disease) * Any increased dose of corticosteroids or other immunosuppressive medication including cyclophosphamide, mycophenolate, leflunomide, calcineurin inhibitors, azathioprine, methotrexate, or use of biological agents regardless of duration, with the past six months * Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection history: seropositivity of HBV surface antigen (HBsAg) or HCV antibodies (HCV-Ab) * Women who are pregnant or breastfeeding * Women with childbearing potential or their male partners, who refuse to use an effective birth control method

Outcomes

Primary Outcomes

The number of patients achieving sustained Renal Response(RR)

Sustained RR is defined as satisfying all of the following criteria: 1)Proteinuria is improved by ≥50% compared with baseline 2)24-hr urine protein \< 1g 3)Serum creatinine is not higher than 15% above baseline level 4)No occurrence of non-renal disease flare after achieving response to treatment.

Time frame: at the end of 12 weeks (3 months) from baseline

Secondary Outcomes

Complete renal remission

1. 24-hr urine protein\<0.3g/day or urine Protein-Creatinine ratio (uPCR)\<300mg/g 2. Serum creatinine not higher than 15% above baseline level

Time frame: at the end of 12 weeks (3 months) from baseline

Partial renal remission

1. 24-hr urine protein\<3.5g/day or uPCR\<3500mg/g 2. Serum creatinine not higher than 15% above baseline level

Time frame: at the end of 12 weeks (3 months) from baseline

Rate of non-renal flare

Central nervous system or other severe organ manifestations of SLE that necessitate aggressive immunosuppressive therapy on its own