Clinical trial NCT05514015: Clinical Study of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in the Treatment of Primary Membranous Nephropathy
Official title: A Prospective, Randomized, Multicenter Clinical Trial Comparing the Efficacy and Safety of Rituximab Combined With Corticosteroids or Rituximab Monotherapy in Primary Membranous Nephropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Primary Membranous Nephropathy
Keywords: rituximab
Primary membranous nephropathy
rituximab combined with corticosteroids
safety
remission
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2022-08-24
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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).

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.

The duration of the entire clinical study was 36 months from the date of project initiation.

Duration of visits: 2 years

Eligibility criteria: Inclusion Criteria

1. Men and women aged 18-75 years;
2. Patients diagnosed as primary membranous nephropathy (PMN) by renal biopsy;
3. After treatment with ACE inhibitors or ARBs for at least 3 months, the following two points were met (unless intolerance to ACE inhibitors or ARBs, contraindications, hypotension that may cause side effects, or the investigator judged that the patient was 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 months is 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 be postmenopausal or postoperatively infertile or on medical contraception (considering the potential risk of thromboembolism in patients with kidney disease); 6. Subjects voluntarily signed the informed consent form;

Exclusion Criteria:

1. Patients with type 1 diabetes mellitus or type 2 diabetes mellitus complicated with diabetic nephropathy. Patients with a recent history of steroid-induced diabetes were eligible if renal biopsies show no evidence of secondary diabetic nephropathy within 6 months before the screening period
2. Patients with secondary membranous nephropathy (such as hepatitis B and C, systemic lupus erythematosus, drug therapy, malignant tumors and other secondary causes);
3. Previous treatment with rituximab, steroids, alkylating agents, calcineurin inhibitors, synthetic ACTH, mycophenolate (MMF), and azathioprine;
4. Receipt of any other study medication (within the last month);
5. Suspected or known allergy or immune reaction to rituximab, corticosteroids or any of their components (including excipients);
6. Active infection, such as active hepatitis B or hepatitis C, tuberculosis (evidence of active tuberculosis infection within 1 year), or human immunodeficiency virus HIV infection (positive for anti-HIV antibodies), etc.
7. A history of immunodeficiency, including other acquired or congenital immunodeficiency diseases, or organ transplantation;
8. Females with a positive pregnancy screening test or lactating or planning to become pregnant in the next 24 months. Female or male patients who were unwilling to use contraceptive methods throughout the study;
9. A history of mental illness;
10. 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) Aspartate aminotransferase (AST) or amino aminotransferase (ALT) \> 2.5× upper limit of normal except in relation to the primary disease; 11. Very high-risk patients: presenting with life-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.

Primary outcomes:
measure: The complete response rate at 12 months;
timeFrame: 12 months
Secondary outcomes:
measure: Response rates at 6, 12, 18 and 24 months (including the proportion of participants with complete response and partial response);
timeFrame: 24 months
measure: Median remission time;
timeFrame: 24 months
measure: Proportion of patients without recurrence at 12, 18 and 24 months;
timeFrame: 24 months
measure: Median non-recurrence time;
timeFrame: 24 months
measure: Cumulative dose of glucocorticoids;
timeFrame: 24 months
measure: CD19+ cell count, anti-PLA2R antibody expression level;
timeFrame: 24 months
measure: Renal function index: eGFR;
timeFrame: 24 months
measure: Incidence of adverse events;
timeFrame: 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Wei Chen
state: Guangdong
Study officials:
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