Sirolimus in Treatment of Proteinuric Flares of Lupus Nephritis

NCT04892212 | Unknown Phase 2

• 1 other identifier: HS-2743
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Lupus Nephritis; Immunosuppression; Effect of Drug

Keywords

Sirolimus; Lupus Nephritis; Renal Flare

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (14)

• Complete renal remission

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

• Partial renal remission

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

• Rate of non-renal flare

  during the 3-month follow up

• Safety and tolerability of study medications

  during the 3-month follow up

• Increase of serum creatinine level>15% from baseline

  during the 3-month follow up

Study Arms (1)

Sirolimus group

EXPERIMENTAL

1. The initial dose of sirolimus is 1mg/day. And the serum trough level of sirolimus is monitored at Week 2, Week 4, Week 8, and Week 12，respectively. The target serum trough level of sirolimus is 5-8 ng/mL. The dose of sirolimus is titrated according to therapeutic drug level monitoring. 2. The previous immunosuppressive medication is not allowed to be changed during the 3-month follow-up, unless premature discontinuation from study.

Drug: Sirolimus

Interventions

Sirolimus DRUG

The daily dose of sirolimus is divided twice.

Also known as: Rapamycin

Sirolimus group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 :
• 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
• No hypoalbuminemia: serum albumin ≥35g/L
• Stable renal function: serum creatinine\<25% increase above the level at the time of renal disease remission
• Eligible to sign informed-consent independently

You may not qualify if:

• 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

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• North China Pharmaceutical Group Corporation: collaborator

Related Publications (5)

• Yap DYH, Tang C, Chan GCW, Kwan LPY, Ma MKM, Mok MMY, Chan TM. Longterm Data on Sirolimus Treatment in Patients with Lupus Nephritis. J Rheumatol. 2018 Dec;45(12):1663-1670. doi: 10.3899/jrheum.180507. Epub 2018 Oct 1.

  PMID: 30275264 BACKGROUND

• Lai ZW, Kelly R, Winans T, Marchena I, Shadakshari A, Yu J, Dawood M, Garcia R, Tily H, Francis L, Faraone SV, Phillips PE, Perl A. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet. 2018 Mar 24;391(10126):1186-1196. doi: 10.1016/S0140-6736(18)30485-9. Epub 2018 Mar 15.

  PMID: 29551338 BACKGROUND

• Eriksson P, Wallin P, Sjowall C. Clinical Experience of Sirolimus Regarding Efficacy and Safety in Systemic Lupus Erythematosus. Front Pharmacol. 2019 Feb 6;10:82. doi: 10.3389/fphar.2019.00082. eCollection 2019.

  PMID: 30787878 BACKGROUND

• Esatoglu SN, Seyahi E. Is sirolimus a treatment option for patients with systemic lupus erythematosus? Clin Exp Rheumatol. 2019 Nov-Dec;37 Suppl 122(6):13. Epub 2019 Jul 12. No abstract available.

  PMID: 31376256 BACKGROUND

• Ma MKM, Yung S, Chan TM. mTOR Inhibition and Kidney Diseases. Transplantation. 2018 Feb;102(2S Suppl 1):S32-S40. doi: 10.1097/TP.0000000000001729.

  PMID: 29369972 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lupus Erythematosus, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Xue-mei Li, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Li, MD

CONTACT

86-010-69155058; superchad099@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 19, 2021
• Study Start: June 30, 2021
• Primary Completion: June 30, 2023
• Study Completion: October 30, 2023
• Last Updated: May 19, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share