Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis

NCT05207358 | Recruiting Phase 4

• 1 other identifier: FundeniCI
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to evaluate the efficacy of a therapeutic regimen which decreases glucocorticoid exposure compared with standard therapy in patients with proliferative lupus nephritis during remission induction by evaluating the histological and clinical remission.

Conditions

Lupus Nephritis

Keywords

immunosuppression; glucocorticoids; eurolupus; rituxilup; induction therapy

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with a histological remission

  The primary endpoint is to evaluate the histologic remission at 6 months after initiation of induction treatment assessed by the change in the individual active lesions and in the activity modified NIH score.

  6 months

Secondary Outcomes (11)

• Percentage of participants with a complete renal response

  12 months

• Percentage of patients with severe infectious episodes effects

  24 months

• Cumulative exposure to glucocorticoids

  24 months

• The proportion of patients who obtained a complete renal response

  6, 18 and 24 months

• The proportion of patients who obtained a partial renal response

  6, 12, 18, 24 months

Study Arms (2)

RITUXILUP regimen

EXPERIMENTAL

\- 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.

Drug: Rituximab; Drug: Mycophenolate Mofetil

EUROLUPUS regimen (Standard therapy)

OTHER

3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.

Drug: Cyclophosphamide; Drug: Corticosteroids

Interventions

Rituximab DRUG

2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15.

RITUXILUP regimen

Mycophenolate Mofetil DRUG

Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.

RITUXILUP regimen

Cyclophosphamide DRUG

All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.

EUROLUPUS regimen (Standard therapy)

Corticosteroids DRUG

3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment.

EUROLUPUS regimen (Standard therapy)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of the patient between 18 and 80 years,
• Patients diagnosed with systemic lupus erythematosus according to ACR 1997 or SLICC-2012 criteria
• Diagnosis of proliferative lupus nephritis class III, IV +/- V (confirmed by renal biopsy and classified according to ISN / RPS);
• Estimated glomerular filtration rate by CKD-EPI\> 30 ml / min / 1.73 sqm
• Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm but\> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score) \<6
• Absence of contraindications to the use of Methylprednisolone, Mycophenolate mofetil, oral corticosteroids or Rituximab
• Ability to provide informed consent

You may not qualify if:

• The patient's age under 18 years
• Patients with life-threatening complications (e.g. Cerebritis)
• Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm
• Estimated glomerular filtration rate by CKD-EPI \<30 ml / min / 1.73 sqm but\> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score)\> 6
• Presence of pregnancy / lactation
• Patients who have received more than 2 g of Methylprednisolone intravenously in the last 4 weeks
• Use in the last 3 months of biological therapy
• Use of intravenous immunoglobulins / plasmapheresis in the last 6 months
• The presence of an active infection
• History of neoplasia
• Comorbidities requiring systemic corticosteroid therapy
• Non-adhesion

Sponsors & Collaborators

• Institutul Clinic Fundeni: lead

Study Sites (1)

Fundeni Clinical Institute

Bucharest, 022328, Romania

RECRUITING

Related Publications (10)

• Parikh SV, Almaani S, Brodsky S, Rovin BH. Update on Lupus Nephritis: Core Curriculum 2020. Am J Kidney Dis. 2020 Aug;76(2):265-281. doi: 10.1053/j.ajkd.2019.10.017. Epub 2020 Mar 24.

  PMID: 32220510 BACKGROUND

• Pepper R, Griffith M, Kirwan C, Levy J, Taube D, Pusey C, Lightstone L, Cairns T. Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids. Nephrol Dial Transplant. 2009 Dec;24(12):3717-23. doi: 10.1093/ndt/gfp336. Epub 2009 Jul 17.

  PMID: 19617257 BACKGROUND

• Fanouriakis A, Bertsias G. Changing paradigms in the treatment of systemic lupus erythematosus. Lupus Sci Med. 2019 Feb 8;6(1):e000310. doi: 10.1136/lupus-2018-000310. eCollection 2019.

  PMID: 31168398 BACKGROUND

• Parikh SV, Rovin BH. Current and Emerging Therapies for Lupus Nephritis. J Am Soc Nephrol. 2016 Oct;27(10):2929-2939. doi: 10.1681/ASN.2016040415. Epub 2016 Jun 9.

  PMID: 27283496 BACKGROUND

• Catapano F, Chaudhry AN, Jones RB, Smith KG, Jayne DW. Long-term efficacy and safety of rituximab in refractory and relapsing systemic lupus erythematosus. Nephrol Dial Transplant. 2010 Nov;25(11):3586-92. doi: 10.1093/ndt/gfq256. Epub 2010 May 11.

  PMID: 20466686 BACKGROUND

• Rovin BH, Furie R, Latinis K, Looney RJ, Fervenza FC, Sanchez-Guerrero J, Maciuca R, Zhang D, Garg JP, Brunetta P, Appel G; LUNAR Investigator Group. Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study. Arthritis Rheum. 2012 Apr;64(4):1215-26. doi: 10.1002/art.34359. Epub 2012 Jan 9.

  PMID: 22231479 BACKGROUND

• Tamirou F, Houssiau FA. Management of Lupus Nephritis. J Clin Med. 2021 Feb 9;10(4):670. doi: 10.3390/jcm10040670.

  PMID: 33572385 BACKGROUND

• Condon MB, Ashby D, Pepper RJ, Cook HT, Levy JB, Griffith M, Cairns TD, Lightstone L. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013 Aug;72(8):1280-6. doi: 10.1136/annrheumdis-2012-202844. Epub 2013 Jun 5.

  PMID: 23740227 BACKGROUND

• Morales E, Galindo M, Trujillo H, Praga M. Update on Lupus Nephritis: Looking for a New Vision. Nephron. 2021;145(1):1-13. doi: 10.1159/000511268. Epub 2020 Nov 4.

  PMID: 33147587 BACKGROUND

• Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, D'Agati VD, Ferrario F, Haas M, Jennette JC, Joh K, Nast CC, Noel LH, Rijnink EC, Roberts ISD, Seshan SV, Sethi S, Fogo AB. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018 Apr;93(4):789-796. doi: 10.1016/j.kint.2017.11.023. Epub 2018 Feb 16.

  PMID: 29459092 BACKGROUND

MeSH Terms

Conditions

Lupus Nephritis

Interventions

Rituximab; Mycophenolic Acid; Cyclophosphamide; Adrenal Cortex Hormones

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Gener Ismail, MD, PhD

  Institutul Clinic Fundeni

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Bogdan Obrisca, MD, PhD

CONTACT

0040721256797; obriscabogdan@yahoo.com

Alexandra Vornicu, MD

CONTACT

0040756203773; vornicu.alexandra@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assist. Prof.

Study Record Dates

• First Submitted: December 7, 2021
• First Posted: January 26, 2022
• Study Start: March 2, 2022
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 3, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Within 12 months of publishing the results of the primary endpoints of the study

Locations

RO (1)