Effectiveness of Mycophenolate Mofetil Combined With Tacrolimus for Steroid Tapering in Systemic Lupus Erythematosus

NCT05916781 | Recruiting Phase 4

• 1 other identifier: CSTAR008
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine whether mycophenolate mofetil(MMF) combined with tacrolimus(TAC) can maintain remission in patients with lupus nephritis (LN) who have reached treatment targets after steroid tapering. The main question\[s\] it aims to answer are:

• The efficacy, safety and tolerability of MMF combined with TAC regimen in the treatment of LN patients in the maintenance period.
• The influence of low-dose steroid on carotid intima thickness (CIMT).
• The omics and cell-free RNA (cfRNA) spectral differences related to lupus flare.
• The differences in health economics between steroid tapering and steroid maintenance patients. Participants will be randomly assigned into 2 groups. In the steroid tapering group, participants will take MMF+TAC treatment without steroid for 1 year, and participants who stop steroid treatment without lupus flare will be randomly assigned to monotherapy with MMF or TAC. In the steroid maintenance group, participants will take MMF+TAC+steroid for 1 year, and participants without lupus flare will stop the use of steroid for 6 months. Participants without lupus flare after the stop of steroid will be randomly assigned to monotherapy with MMF or TAC.

Conditions

Systemic Lupus Erythematosus; Lupus Nephritis

Keywords

mycophenolate mofetil; tacrolimus; steroid tapering; systemic lupus erythematosus; lupus nephritis

Outcome Measures

Primary Outcomes (1)

• The 1-year flare rate of lupus nephritis participants who reach the treatment target and accept MMF+TAC remedy tapering steroid in the maintenance period.

  If the DORIS (Definition of Remission In SLE) is not sustained, the patient is considered to have lupus flare. Lupus flare can be further evaluated according to SELENA-SLEDAI Flare Index (SFI). Lupus nephritis flare can be further evaluated as flare of proteinuria and flare of nephritis.

  6th~18th month

Secondary Outcomes (7)

• The 1-year flare rate of lupus nephritis participants who accept MMF or TAC monotherapy.

  18th~30th month

• Lupus flare (as assessed by SLEDAI and PGA) in SLE patients during the maintenance period after steroid tapering.

  6th~30th month

• The changes of serum activity markers (anti-dsDNA antibody and C3 level) in SLE patients after steroid tapering.

  6th~30th month

• Proportion of SLE patients with irreversible organ damage (assessed by SLICC/SDI) after steroid tapering.

  6th~30th month

• Changes in carotid intima-media thickness after steroid tapering.

  6th~30th month

Study Arms (2)

steroid tapering group

EXPERIMENTAL

0\~6th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) + steroid (1 pill/d) 6th\~18th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) 18th\~30th month: Participants who stop steroid treatment and do not flare will be randomly assigned to monotherapy with mycophenolate mofetil or tacrolimus

Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Glucocorticoid

steroid maintenance group

ACTIVE COMPARATOR

0\~18th month: mycophenolate mofetil (1g/d) + tacrolimus (2.0mg/d) + steroid (1 pill/d) 18th\~24th month: Participants who do not flare will stop the use of steroid. 24th\~30th month: Participants who do not flare will be randomly assigned to monotherapy with mycophenolate mofetil or tacrolimus

Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Drug: Glucocorticoid

Interventions

Mycophenolate Mofetil DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC. Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Also known as: MMF

steroid maintenance group; steroid tapering group

Tacrolimus DRUG

Participants in steroid tapering group will take MMF+TAC during the first 18 months. After 18 months, participants without lupus flare will randomly stop MMF or TAC. Participants in steroid maintenance group will take MMF+TAC during the first 24 months. After 24 months, participants without lupus flare will randomly stop MMF or TAC.

Also known as: TAC

steroid maintenance group; steroid tapering group

Glucocorticoid DRUG

Participants in steroid tapering group will stop taking glucocorticoid after the first 6 months. Participants in steroid maintenance group will consistently take glucocorticoid for 18 months, and stop the use of glucocorticoid after 18 months if they do not flare.

steroid maintenance group; steroid tapering group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Systemic lupus erythematosus participants diagnosed with 2019 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, fulfilled with American College of Rheumatology (ACR) lupus nephritis definition, and have reached treatment target (accord with lupus nephritis clinical remission and DORIS) for at least 6 months. The target is defined as: (1)24h urine protein ≤0.5g/d；(2)stable of improved renal function (baseline creatinine ±10% or decrease 15%)；(3)clinical SLE Disease Activity Index (cSLEDAI) =0 (all scores are required zero, except hypocomplementemia and anti-dsDNA antibody positivity)；(4)PGA score (Physician Global Assessment)\<0.5; (5)prednisone or equivalent steroid dose≤5mg/d；(6)stable use of immunosuppressants and antimalarial drugs; (7)no use of biological agents.
• According to the physician, the participant can accept this treatment.
• The participant is willing to join this clinical trial, has good compliance, and could understand and sign the informed consent before the study begins.

You may not qualify if:

• SLE complicated with important organ dysfunction, including consciousness disorder, cognitive disorder, renal dysfunction, heart dysfunction (NYHA class 3, 4), pulmonary arterial hypertension, and interstitial lung disease.
• SLE with active vital organ disease (not satisfied with DORIS), including but not limited to active neuropsychiatric systemic lupus erythematosus, lupus nephritis, thrombocytopenia, hemolytic anemia, myocardial involvement, gastrointestinal involvement, etc.
• Participants who are allergic to or intolerant with mycophenolate mofetil or tacrolimus.
• Participants with acute and chronic infections requiring anti-infective treatment, including but not limited to tuberculosis infection, Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection, Human Immunodeficiency Virus (HIV) infection, and Cytomegalovirus (CMV) infection.
• Participants who are pregnant or planning to become pregnant.
• Participants who have used biological agents within 6 months before enrollment.
• The researcher considers any condition that may cause the participant to be unable to complete the study or bring an obvious risk to the participant.

Sponsors & Collaborators

• Chinese SLE Treatment And Research Group: lead
• Peking Union Medical College Hospital: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, 100730, China

RECRUITING

Related Publications (13)

• Murimi-Worstell IB, Lin DH, Nab H, Kan HJ, Onasanya O, Tierce JC, Wang X, Desta B, Alexander GC, Hammond ER. Association between organ damage and mortality in systemic lupus erythematosus: a systematic review and meta-analysis. BMJ Open. 2020 May 21;10(5):e031850. doi: 10.1136/bmjopen-2019-031850.

  PMID: 32444429 BACKGROUND

• Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum. 2000 Aug;43(8):1801-8. doi: 10.1002/1529-0131(200008)43:83.0.CO;2-O.

  PMID: 10943870 BACKGROUND

• Fanouriakis A, Kostopoulou M, Alunno A, Aringer M, Bajema I, Boletis JN, Cervera R, Doria A, Gordon C, Govoni M, Houssiau F, Jayne D, Kouloumas M, Kuhn A, Larsen JL, Lerstrom K, Moroni G, Mosca M, Schneider M, Smolen JS, Svenungsson E, Tesar V, Tincani A, Troldborg A, van Vollenhoven R, Wenzel J, Bertsias G, Boumpas DT. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019 Jun;78(6):736-745. doi: 10.1136/annrheumdis-2019-215089. Epub 2019 Mar 29.

  PMID: 30926722 BACKGROUND

• Tani C, Elefante E, Signorini V, Zucchi D, Lorenzoni V, Carli L, Stagnaro C, Ferro F, Mosca M. Glucocorticoid withdrawal in systemic lupus erythematosus: are remission and low disease activity reliable starting points for stopping treatment? A real-life experience. RMD Open. 2019 Jun 11;5(2):e000916. doi: 10.1136/rmdopen-2019-000916. eCollection 2019.

  PMID: 31275608 BACKGROUND

• Mathian A, Pha M, Haroche J, Cohen-Aubart F, Hie M, Pineton de Chambrun M, Boutin THD, Miyara M, Gorochov G, Yssel H, Cherin P, Devilliers H, Amoura Z. Withdrawal of low-dose prednisone in SLE patients with a clinically quiescent disease for more than 1 year: a randomised clinical trial. Ann Rheum Dis. 2020 Mar;79(3):339-346. doi: 10.1136/annrheumdis-2019-216303. Epub 2019 Dec 18.

  PMID: 31852672 BACKGROUND

• Villarroel MC, Hidalgo M, Jimeno A. Mycophenolate mofetil: An update. Drugs Today (Barc). 2009 Jul;45(7):521-32. doi: 10.1358/dot.2009.45.7.1384878.

  PMID: 19834629 BACKGROUND

• Fanouriakis A, Kostopoulou M, Cheema K, Anders HJ, Aringer M, Bajema I, Boletis J, Frangou E, Houssiau FA, Hollis J, Karras A, Marchiori F, Marks SD, Moroni G, Mosca M, Parodis I, Praga M, Schneider M, Smolen JS, Tesar V, Trachana M, van Vollenhoven RF, Voskuyl AE, Teng YKO, van Leew B, Bertsias G, Jayne D, Boumpas DT. 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Ann Rheum Dis. 2020 Jun;79(6):713-723. doi: 10.1136/annrheumdis-2020-216924. Epub 2020 Mar 27.

  PMID: 32220834 BACKGROUND

• Mok CC. Mycophenolate mofetil for non-renal manifestations of systemic lupus erythematosus: a systematic review. Scand J Rheumatol. 2007 Sep-Oct;36(5):329-37. doi: 10.1080/03009740701607042.

  PMID: 17963161 BACKGROUND

• Broen JCA, van Laar JM. Mycophenolate mofetil, azathioprine and tacrolimus: mechanisms in rheumatology. Nat Rev Rheumatol. 2020 Mar;16(3):167-178. doi: 10.1038/s41584-020-0374-8. Epub 2020 Feb 13.

  PMID: 32055040 BACKGROUND

• Yoon KH. Efficacy and cytokine modulating effects of tacrolimus in systemic lupus erythematosus: a review. J Biomed Biotechnol. 2010;2010:686480. doi: 10.1155/2010/686480. Epub 2010 Jun 28.

  PMID: 20625508 BACKGROUND

• Hannah J, Casian A, D'Cruz D. Tacrolimus use in lupus nephritis: A systematic review and meta-analysis. Autoimmun Rev. 2016 Jan;15(1):93-101. doi: 10.1016/j.autrev.2015.09.006. Epub 2015 Sep 30.

  PMID: 26427983 BACKGROUND

• Zhang H, Liu Z, Zhou M, Liu Z, Chen J, Xing C, Lin H, Ni Z, Fu P, Liu F, Chen N, He Y, Liu J, Zeng C, Liu Z. Multitarget Therapy for Maintenance Treatment of Lupus Nephritis. J Am Soc Nephrol. 2017 Dec;28(12):3671-3678. doi: 10.1681/ASN.2017030263. Epub 2017 Jul 31.

  PMID: 28760751 BACKGROUND

• Peng L, Wang Z, Li M, Wang Y, Xu D, Wang Q, Zhang S, Zhao J, Tian X, Zeng X. Flares in Chinese systemic lupus erythematosus patients: a 6-year follow-up study. Clin Rheumatol. 2017 Dec;36(12):2727-2732. doi: 10.1007/s10067-017-3842-z. Epub 2017 Sep 19.

  PMID: 28929239 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Interventions

Mycophenolic Acid; Tacrolimus; Glucocorticoids

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Macrolides; Lactones; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Mengtao Li, MD

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

Can Huang, MD

CONTACT

86-13426191948; huang_can@yeah.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: First, participants are randomly assigned into 2 groups: steroid tapering group and steroid maintenance group. In steroid tapering group, participants without flare will be assigned into 2 groups: mycophenolate mofetil group and tacrolimus group. In steroid maintenance group, participants without flare will stop the use of steroid for 6 months. Participants without lupus flare after the stop of steroid will be assigned into 2 groups: mycophenolate mofetil group and tacrolimus group.

Study Record Dates

• First Submitted: June 9, 2023
• First Posted: June 23, 2023
• Study Start: July 1, 2023
• Primary Completion: July 31, 2025
• Study Completion (Estimated): July 31, 2026
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)