Clinical trial NCT05839314: Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy
Official title: Effect of Huaier Granule on the Treatment of Idiopathic Membranous Nephropathy: a Multicenter, Randomized, Open-label, Parallel Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Nephropathy
Glomerular Diseases
Idiopathic Membranous Nephropathy
Keywords: Huaier granule
Ciclosporin
Idiopathic membranous nephropathy
Lead sponsor: Chinese PLA General Hospital
Sponsor class: OTHER
Collaborators: name: LinkDoc Technology (Beijing) Co. Ltd.
name: Huazhong University of Science and Technology
First posted: 2023-05-03
Enrollment: 480
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 is a prospective, multicenter, randomized, open-label, parallel controlled study. The purpose of this study is to evaluate the efficacy and safety of Huaier granule on the treatment of idiopathic membranous nephropathy comparing with Ciclosporin soft capsules.

Detailed description: Idiopathic membranous nephropathy (IMN) is a common immune-mediated glomerular disease, accounting for 20% to 36.8% of adult nephrotic syndrome. A third of the patients will experience complete remission spontaneously, and 30%-40% of patients will develop chronic renal failure. The treatment of IMN includes supportive therapy and immunosuppressive therapy. Ciclosporin (CsA) is a kind of calcineurin inhibitor (CNI) recommended by the Kidney disease improving global outcomes (KDIGO) clinical practice guideline for IMN treatment. CsA is effective in inducing remission among patients with steroid-resistant nephrotic IMN, and studies showed the clinical remission rate was 60%-75%. However, it has a high rate of relapse during follow-up in 6-12 months.

Huaier granule is an extract from a medicinal fungus. Previous studies showed that Huaier granule reduced the excretion of proteinuria, inhibited inflammation and cellular transdifferentiation, and protect renal function.

In this study, about 30 research centers will participate. We plan to enroll 480 participants (240 cases in the experimental group and 240 cases in the control group). The planned length of patient recruitment enrolment will be 2 years and the total length of visits be 1 year.

Eligibility criteria: Inclusion Criteria:

* Renal biopsy was performed before randomization and pathologically diagnosed as idiopathic membranous nephropathy;
* Anti-phospholipase a2 receptor (PLA2R) antibody is positive;
* Aged from 18 to 75, either sex;
* Tolerable doses of RASI were received for ≥4 weeks before randomization, nephrotic syndrome was not in remission and 24-hour urinary protein level was ≥3.5g/24h and \< 8.0g/24h;
* The eGFR≥45ml/min/1.73m2 (Measured at least twice in 2 weeks);
* The patient is willing to sign the informed consent form.

Exclusion Criteria:

* Diagnosed as secondary membranous nephropathy;
* Rapidly progressive membranous nephropathy (eGFR decreased by 50 % compared with the baseline level within 3 months);
* Receiving renal replacement therapy;
* Diabetes and glycosylated hemoglobin (HbA1c) levels ≥ 7.0%;
* Hypertension is not well controlled (systolic blood pressure\>160mmHg or diastolic blood pressure\>100mmHg);
* The level of serum albumin≤20g/L;
* Resistance to treatment with CsA or other CNI, rituximab (RTX) or alkylating agents; complete remission or partial remission was obtained after treatment with CNI, RTX, or alkylating agents but there was a history of relapse within 3 months；
* Suspected infection by imaging and/or laboratory tests;
* Infectious diseases, such as hepatitis B, hepatitis C, AIDS, tuberculosis;
* History of malignant tumor;
* Hepatic dysfunction: aspartate aminotransferase (AST) concentration and alanine aminotransferase (ALT) concentration of \> 1.5 × upper limit of normal;
* Allergic to Huaier granule or Ciclosporin soft capsules;
* Previous CNI treatment was ineffective;
* Complicate with any diseases that may affect efficacy and safety evaluation;
* Pregnant or lactating women, and patients (male or female) with fertility plans or unwilling to take effective contraceptive measures;
* Participating in other clinical trials or participated in other clinical studies within 3 months;
* According to the researchers, patients have diseases or conditions that increase the difficulty of enrollment or probability of loss to follow-up, such as mental illness, frequent changes in residence and work, etc.

Primary outcomes:
measure: Overall clinical remission rate at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
Secondary outcomes:
measure: Rate of complete remission at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Rate of partial remission at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Median time to achieve complete remission
timeFrame: Start of randomization until 96 weeks
measure: Median time to achieve partial remission
timeFrame: Start of randomization until 96 weeks
measure: Median time of the first relapse of nephrotic syndrome for patients who achieve complete remission or partial remission
timeFrame: Start of randomization until 96 weeks
measure: Proportion of patients with relapse of nephrotic syndrome
timeFrame: Start of randomization until 96 weeks
measure: Rate of treatment failure at the end of the study
timeFrame: Start of randomization until 96 weeks
measure: The proportion of reappearance proteinuria (but not reach nephrotic syndrome) for patients with complete response
timeFrame: Start of randomization until 96 weeks
measure: The 24-hour urinary protein level and changes from baseline at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: The serum albumin level and changes from baseline at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Changes of serum creatinine at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Changes of blood urea nitrogen at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Changes of serum uric acid at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Changes of serum blood lipid level at 24, 48, 96 week
timeFrame: Start of randomization until 96 weeks
measure: The level and changes of estimated glomerular filtration rate (eGFR) calculating using the CKD-EPI formula at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: Percentage of patients who serum creatinine doubled for 12 weeks, progress to end-stage renal disease, or receive renal replacement therapy
timeFrame: Start of randomization until 96 weeks
measure: The number and proportion of patients who died for any reason
timeFrame: Start of randomization until 96 weeks
measure: The level of phospholipase A2 receptor (PLA2R) and changes from baseline at 24, 48, 96 weeks
timeFrame: Start of randomization until 96 weeks
measure: The level and changes of immunoglobulin and complement
timeFrame: Start of randomization until 96 weeks
measure: Incidence and severity of adverse events (AE) and serious adverse events (SAE)
timeFrame: Start of randomization until 96 weeks
measure: Incidence and severity of adverse reactions (ADR), serious adverse reactions (SADR)
timeFrame: Start of randomization until 96 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Chinese PLA general hospital
state: Beijing
Study officials:
affiliation: Chinese PLA General Hospital, Beijing, China
name: Xiangmei Chen, PhD
role: PRINCIPAL_INVESTIGATOR
References: