Clinical Study of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in the Treatment of Primary Membranous Nephropathy

Phase

Condition

Nephrotic Syndrome

Idiopathic Membranous Nephropathy

Glomerulonephritis

Treatment

rituximab combined with corticosteroids

rituximab

Clinical Study ID

NCT05514015

HLK-202302

Ages 18-75
All Genders

Study Summary

This was a prospective, randomized, multicenter clinical trial. Seventy-eight patients with primary membranous nephropathy (PMN) were randomly divided into intervention or control group. Intervention group was given rituximab combined with corticosteroids in induction therapy and the control group was given rituximab monotherapy. After 6 months, patients who had decreased 24h urinary protein by > 25% but did not achieve CR were given rituximab maintenance therapy. The complete response rate at 12 months was measured.

Eligibility Criteria

Inclusion

Inclusion Criteria

Men and women aged 18-75 years;
Patients diagnosed as primary membranous nephropathy (PMN) by renal biopsy;
After treatment with ACE inhibitors or ARBs for at least 3 months, the following twopoints were met (unless intolerance to ACE inhibitors or ARBs, contraindications,hypotension that may cause side effects, or the investigator judged that the patientwas not suitable for RAS inhibitors):

(1) Those who have an average 24-hour urine protein ≥ 3.5g twice a week, or an average 24-hour urine protein ≥ 5g twice in 14 days, the requirement of RASi for at least 3 monthsis not required (2) Blood pressure≤ 130/80mmHg, 4. Glomerular filtration rate (eGFR) ≥30mL/min/1.73m2 (calculated according to the CKD-EPI formula) 5. If female, must bepostmenopausal or postoperatively infertile or on medical contraception (considering thepotential risk of thromboembolism in patients with kidney disease); 6. Subjects voluntarilysigned the informed consent form;

Exclusion

Exclusion Criteria:

Patients with type 1 diabetes mellitus or type 2 diabetes mellitus complicated withdiabetic nephropathy. Patients with a recent history of steroid-induced diabetes wereeligible if renal biopsies show no evidence of secondary diabetic nephropathy within 6months before the screening period
Patients with secondary membranous nephropathy (such as hepatitis B and C, systemiclupus erythematosus, drug therapy, malignant tumors and other secondary causes);
Previous treatment with rituximab, steroids, alkylating agents, calcineurininhibitors, synthetic ACTH, mycophenolate (MMF), and azathioprine;
Receipt of any other study medication (within the last month);
Suspected or known allergy or immune reaction to rituximab, corticosteroids or any oftheir components (including excipients);
Active infection, such as active hepatitis B or hepatitis C, tuberculosis (evidence ofactive tuberculosis infection within 1 year), or human immunodeficiency virus HIVinfection (positive for anti-HIV antibodies), etc.
A history of immunodeficiency, including other acquired or congenital immunodeficiencydiseases, or organ transplantation;
Females with a positive pregnancy screening test or lactating or planning to becomepregnant in the next 24 months. Female or male patients who were unwilling to usecontraceptive methods throughout the study;
A history of mental illness;
Laboratory tests that meet the following criteria need to be excluded:

(1) Hemoglobin<80g/L; (2) Platelet < 80×109/L; (3) Neutrophil <1.0×109/L; (4) Aspartateaminotransferase (AST) or amino aminotransferase (ALT) > 2.5× upper limit of normal exceptin relation to the primary disease; 11. Very high-risk patients: presenting withlife-threatening nephrotic syndrome, or unexplained rapid deterioration of renal function 12. Any patient judged by the investigator to be unsuitable for inclusion in the trial.

Study Design

rituximab combined with corticosteroids

March 29, 2024

December 31, 2026

Study Description

Study design A prospective, randomized , multicenter clinical study

Outcomes

Primary objective To evaluate the efficacy of rituximab combined with corticosteroids or rituximab monotherapy in primary membranous nephropathy
Secondary Objectives The safety of rituximab combined with corticosteroids or rituximab monotherapy in primary membranous nephropathy;

Primary outcome The complete response rate at 12 months;

Secondary outcomes
1. Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);
2. Median remission time;
3. Proportion of patients without recurrence at 12, 18 and 24 months;
4. Median non-recurrence time;
5. Cumulative dose of glucocorticoids;
6. CD19+ cell count, anti-PLA2R antibody expression level;
7. Renal function index: eGFR;
8. Incidence of adverse events;
  
  Study population Seventy-eight male or female treatment-naïve primary membranous nephropathy (PMN) patients
  
  Description of the study intervention Intervention group: rituximab combined with corticosteroids: 39 cases. Patients are pretreated with diphenhydramine and dexamethasone 30-60 minutes before rituximab infusion.
Induction therapy:

Rituximab intravenous infusion of 1g, d1, d15, combined with glucocorticoid therapy, oral prednisolone, initial dose of 0.5mg/(kg·d), once a day, after 8 weeks of treatment, reduce by 5mg every 4 weeks until 0.25mg/kg, this dose was maintained for 8 weeks, and then reduced by 2.5mg every 4 weeks, until 5-10mg is maintained, and the total course of treatment was about one year or so;

Consolidation therapy after 6 months: Patients who achieve CR do not require consolidation therapy; Patients who had a 24-hour reduction in proteinuria >25% but did not achieve CR received an additional course of rituximab 1g, D1, D15 (independent of CD19+ cell count).

Patients with less than 25% decrease in proteinuria in 24 hours do not require continued medical therapy, and were considered as treatment failure and withdraw from the trial.

Control group: Rituximab monotherapy: 39 cases,

Treatment regimen: 30-60 minutes before intravenous infusion of rituximab, diphenhydramine 20mg intramuscularly and dexamethasone 5mg intravenously were given for pretreatment.
- Induction therapy:Rituximab intravenous infusion of 1g, d1, d15
- Consolidation therapy after 6 months:

Patients who achieve CR do not require consolidation therapy; Patients who had a 24-hour reduction in proteinuria >25% but did not achieve CR received an additional course of rituximab 1g, D1, D15 (independent of CD19+ cell count).