Efficacy and SafetyNCT05532111
Efficacy and Safety of the Treatment of Primary Membranous Nephropathy: A Randomized Clinical Trial
A study testing Rituximab combined with tacrolimus induction + rituximab maintenance, Rituximab combined with tacrolimus induction + tacrolimus maintenance and Glucocorticoid combined with cyclophosphamide induction + maintenance in people with Efficacy and Safety, run by RenJi Hospital.
Trial summary
1. Main purpose: To evaluate the efficacy and safety of rituximab combined with tacrolimus in the treatment of intermediate and high-risk primary membranous nephropathy 2. Secondary research purposes: To describe the survival of patients with intermediate and high-risk primary membranous nephropathy treated with… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Efficacy and Safety
- What is being tested?
- Rituximab combined with tacrolimus induction + rituximab maintenance, Rituximab combined with tacrolimus induction + tacrolimus maintenance and Glucocorticoid combined with cyclophosphamide induction + maintenance
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- 1 Sep 2022to 30 Sep 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- gender is not limited；
- Age 18-75；
- Kidney biopsy pathology suggests primary membranous nephropathy;
- Serological or histological PLA2R positive;
- 24-hour urine protein quantification ≥3.5g/d and serum albumin <30g/L;
- Glomerular filtration rate [eGRF (CKD-EPI formula)] ≥ 45ml/min/1.73m2;
Who cannot join
- Secondary membranous nephropathy (tumor-related, lupus-related, hepatitis B-related, infection-related, drug-related, etc.);
- Renal biopsy pathology showed severe tubulointerstitial lesions;
- Severe infection, severe cardiac insufficiency, severe hepatic insufficiency, gastrointestinal bleeding, ketoacidosis and other life-threatening complications within one month;
- Glucocorticoids and/or immunosuppressive therapy (cyclophosphamide, MMF, tacrolimus) within 3 months;
- Have a history of kidney transplantation;
- Breastfeeding or pregnant women;
- Patients with mental disorders or unable to cooperate ;
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Efficacy and Safety of Rituximab Combined With Tacrolimus in the Treatment of Intermediate-to-high Risk Primary Membranous Nephropathy: A Randomized Clinical Trial
- Main purpose: To evaluate the efficacy and safety of rituximab combined with tacrolimus in the treatment of intermediate and high-risk primary membranous nephropathy
- Secondary research purposes: To describe the survival of patients with intermediate and high-risk primary membranous nephropathy treated with rituximab combined with tacrolimus; To describe renal survival in patients with intermediate and high-risk primary membranous nephropathy treated with rituximab combined with tacrolimus;
- Exploratory research purposes:
Feasibility of glucocorticoids-free therapy (rituximab combined with tacrolimus) in the treatment of intermediate and high-risk primary membranous nephropathy
Read the detailed description
Membranous nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, with a peak incidence in middle-aged and elderly patients. The typical pathological features are: thickening of the basement membrane, deposition of immunofluorescent IgG with or without C3 along the basement membrane, and deposition of epithelial electron-dense deposits. It is divided into primary MN (Primary membranous nephropathy, PMN) and secondary MN (which can be secondary to connective tissue diseases, infections, malignant tumors, drugs/toxicants, etc.). Clinically, it usually presents with massive proteinuria and edema, and some patients gradually progress to end stage renal disease (ESRD).
In recent years, the prevalence of PMN in China has increased year by year. It has been reported that the proportion of MN in primary glomerular diseases in renal biopsy increased from 10.4% in 2003-2006 to 24.1% in 2011-2014 [1], and some trend of youth.
For a long time, the treatment of PMN has mainly used glucocorticoids combined with alkylating agents or calcineurin inhibitors (CNIs). With the continuous exploration and in-depth understanding of the pathogenesis of MN, it has been developed to the molecular level. The KDIGO 2021 Glomerular Disease Management Guidelines are being published [2] Compared with the 2012 KDIGO Glomerular Disease Management Guidelines, the diagnosis and treatment of MN has undergone major changes (Figure 1). Due to the toxicity of alkylating agents and the long-term nephrotoxicity of CNIs, as well as their high risk of relapse when used as monotherapy (with or without prednisone), anti-CD20 biotherapeutics (especially Rituximab, RTX)) is gaining popularity as first-line therapy.
Both international and domestic guidelines recommend that moderate and severe MN require immunosuppressive therapy. RTX is an anti-CD20 monoclonal antibody, which can block the generation of B cells, differentiate into plasma cells, reduce the production of antibodies (such as PLA2R), and avoid processes such as glomerular basement membrane damage. TAC is a calcineurin inhibitor that has been used in PMN for many years. It mainly acts through various mechanisms such as immune regulation and stabilization of the pod cytoskeleton. Two-drug sequential therapy can work from multiple mechanisms, potentially achieving better and faster therapeutic effects.
- Conditions
- Efficacy and Safety
- Being tested
- Rituximab combined with tacrolimus induction + rituximab maintenance, Rituximab combined with tacrolimus induction + tacrolimus maintenance, Glucocorticoid combined with cyclophosphamide induction + maintenance
- Keywords
- Rituximab, Tacrolimus, Primary Membranous Nephropathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rituximab combined with tacrolimus induction + rituximab maintenanceDrug
RT-R group: Rituximab 1 g/time, once in 15 days, × 2 times, combined with tacrolimus, the initial dose is 0.05-0.1 mg/kg/d, 2 times at an interval of 12 hours, orally. Adjust the dose according to the blood concentration (maintain the blood concentration C0 4-8ng/ml). At the end of 24 weeks, tacrolimus was stopped, and rituximab was given 1 g/time × 1 time.
Rituximab combined with tacrolimus induction + tacrolimus maintenanceDrug
RT-T group: Rituximab 1 g/time, once in 15 days, × 2 times, combined with tacrolimus, the initial dose is 0.05-0.1 mg/kg/d, 2 times at an interval of 12 hours, orally. Adjust the dose according to the blood concentration (maintain the blood concentration C0 4-8ng/ml).
Glucocorticoid combined with cyclophosphamide induction + maintenanceDrug
PC-C group: The initial dose of prednisone/prednisolone was 0.5-1 mg/kg/d (the maximum dose was 70 mg/d), and the dose was gradually reduced after 4-8 weeks, and then stopped within 6-9 months. Cyclophosphamide 750mg/m2 (adjusted according to eGFR and other conditions), once a month, intravenous pulse therapy. CTX maintenance therapy.
| Study group | Role | What they receive |
|---|---|---|
| RT-R Group | Experimental | Rituximab combined with tacrolimus induction + rituximab maintenance Receives: Drug: Rituximab combined with tacrolimus induction + rituximab maintenance |
| RT-T Group | Experimental | Rituximab combined with tacrolimus induction + tacrolimus maintenance Receives: Drug: Rituximab combined with tacrolimus induction + tacrolimus maintenance |
| PC-C Group | Experimental | Glucocorticoid combined with cyclophosphamide induction + maintenance Receives: Drug: Glucocorticoid combined with cyclophosphamide induction + maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour urine protein quantification
- Remission: decreased proteinuria. Complete remission (CR): 24HUTP<0.3g/L Partial remission (PR): 24HUTP decreased by >50% and >0.3g/L from baseline
- Invalid: no decrease in proteinuria compared with baseline.
- Recurrence: increased proteinuria (24-hour urine protein quantification ≥3.5g/d) , recurred after reaching CR or PR.
Measured: 48 weeks
serum albumin
- Remission: serum albumin>30g/L
- Invalid: serum albumin <30g/L
- Recurrence: decreased serum albumin, <30g/L, recurred after reaching CR or PR.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2022
- Study start1 Sep 2022 (estimated)
- Primary completion30 Sep 2023 (estimated)
- Study completion30 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Efficacy and SafetyStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05532111
- Sponsor's protocol ID
- IIT-2021-0149
- Status last verified
- Sep 2022
- First submitted
- 1 Sep 2022
- Last updated
- 8 Sep 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Rituximab Combined With Tacrolimus in the Treatment of Intermediate-to-high Risk Primary Membranous Nephropathy: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05532111
- Acronym / sponsor ID
- IIT-2021-0149
- Conditions
- Efficacy and Safety
- Keywords
- Rituximab, Tacrolimus, Primary Membranous Nephropathy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Sep 2022 (estimated)
- Primary completion
- 30 Sep 2023 (estimated)
- Study completion
- 30 Sep 2024 (estimated)
- First posted
- 8 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Main purpose: To evaluate the efficacy and safety of rituximab combined with tacrolimus in the treatment of intermediate and high-risk primary membranous nephropathy
- Secondary research purposes: To describe the survival of patients with intermediate and high-risk primary membranous nephropathy treated with rituximab combined with tacrolimus; To describe renal survival in patients with intermediate and high-risk primary membranous nephropathy treated with rituximab combined with tacrolimus;
- Exploratory research purposes:
Feasibility of glucocorticoids-free therapy (rituximab combined with tacrolimus) in the treatment of intermediate and high-risk primary membranous nephropathy
Detailed description
Membranous nephropathy (MN) is the leading cause of primary nephrotic syndrome in adults, with a peak incidence in middle-aged and elderly patients. The typical pathological features are: thickening of the basement membrane, deposition of immunofluorescent IgG with or without C3 along the basement membrane, and deposition of epithelial electron-dense deposits. It is divided into primary MN (Primary membranous nephropathy, PMN) and secondary MN (which can be secondary to connective tissue diseases, infections, malignant tumors, drugs/toxicants, etc.). Clinically, it usually presents with massive proteinuria and edema, and some patients gradually progress to end stage renal disease (ESRD).
In recent years, the prevalence of PMN in China has increased year by year. It has been reported that the proportion of MN in primary glomerular diseases in renal biopsy increased from 10.4% in 2003-2006 to 24.1% in 2011-2014 [1], and some trend of youth.
For a long time, the treatment of PMN has mainly used glucocorticoids combined with alkylating agents or calcineurin inhibitors (CNIs). With the continuous exploration and in-depth understanding of the pathogenesis of MN, it has been developed to the molecular level. The KDIGO 2021 Glomerular Disease Management Guidelines are being published [2] Compared with the 2012 KDIGO Glomerular Disease Management Guidelines, the diagnosis and treatment of MN has undergone major changes (Figure 1). Due to the toxicity of alkylating agents and the long-term nephrotoxicity of CNIs, as well as their high risk of relapse when used as monotherapy (with or without prednisone), anti-CD20 biotherapeutics (especially Rituximab, RTX)) is gaining popularity as first-line therapy.
Both international and domestic guidelines recommend that moderate and severe MN require immunosuppressive therapy. RTX is an anti-CD20 monoclonal antibody, which can block the generation of B cells, differentiate into plasma cells, reduce the production of antibodies (such as PLA2R), and avoid processes such as glomerular basement membrane damage. TAC is a calcineurin inhibitor that has been used in PMN for many years. It mainly acts through various mechanisms such as immune regulation and stabilization of the pod cytoskeleton. Two-drug sequential therapy can work from multiple mechanisms, potentially achieving better and faster therapeutic effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| RT-R Group | Experimental | Drug: Rituximab combined with tacrolimus induction + rituximab maintenanceRituximab combined with tacrolimus induction + rituximab maintenance |
| RT-T Group | Experimental | Drug: Rituximab combined with tacrolimus induction + tacrolimus maintenanceRituximab combined with tacrolimus induction + tacrolimus maintenance |
| PC-C Group | Experimental | Drug: Glucocorticoid combined with cyclophosphamide induction + maintenanceGlucocorticoid combined with cyclophosphamide induction + maintenance |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- gender is not limited；
- Age 18-75；
- Kidney biopsy pathology suggests primary membranous nephropathy;
- Serological or histological PLA2R positive;
- 24-hour urine protein quantification ≥3.5g/d and serum albumin <30g/L;
Key exclusion criteria (7 listed)
- Secondary membranous nephropathy (tumor-related, lupus-related, hepatitis B-related, infection-related, drug-related, etc.);
- Renal biopsy pathology showed severe tubulointerstitial lesions;
- Severe infection, severe cardiac insufficiency, severe hepatic insufficiency, gastrointestinal bleeding, ketoacidosis and other life-threatening complications within one month;
- Glucocorticoids and/or immunosuppressive therapy (cyclophosphamide, MMF, tacrolimus) within 3 months;
- Have a history of kidney transplantation;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Rituximab combined with tacrolimus induction + rituximab maintenanceRT-R group: Rituximab 1 g/time, once in 15 days, × 2 times, combined with tacrolimus, the initial dose is 0.05-0.1 mg/kg/d, 2 times at an interval of 12 hours, orally. Adjust the dose according to the blood concentration (maintain the blood concentration C0 4-8ng/ml). At the end of 24 weeks, tacrolimus was stopped, and rituximab was given 1 g/time × 1 time. | Drug | RT-R Group |
| Rituximab combined with tacrolimus induction + tacrolimus maintenanceRT-T group: Rituximab 1 g/time, once in 15 days, × 2 times, combined with tacrolimus, the initial dose is 0.05-0.1 mg/kg/d, 2 times at an interval of 12 hours, orally. Adjust the dose according to the blood concentration (maintain the blood concentration C0 4-8ng/ml). | Drug | RT-T Group |
| Glucocorticoid combined with cyclophosphamide induction + maintenancePC-C group: The initial dose of prednisone/prednisolone was 0.5-1 mg/kg/d (the maximum dose was 70 mg/d), and the dose was gradually reduced after 4-8 weeks, and then stopped within 6-9 months. Cyclophosphamide 750mg/m2 (adjusted according to eGFR and other conditions), once a month, intravenous pulse therapy. CTX maintenance therapy. | Drug | PC-C Group |
Primary outcome
24-hour urine protein quantification
Time frame: 48 weeks
1. Remission: decreased proteinuria. Complete remission (CR): 24HUTP<0.3g/L Partial remission (PR): 24HUTP decreased by >50% and >0.3g/L from baseline 2. Invalid: no decrease in proteinuria compared with baseline. 3. Recurrence: increased proteinuria (24-hour urine protein quantification ≥3.5g/d) , recurred after reaching CR or PR.
serum albumin
Time frame: 48 weeks
1. Remission: serum albumin>30g/L 2. Invalid: serum albumin <30g/L 3. Recurrence: decreased serum albumin, <30g/L, recurred after reaching CR or PR.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A study testing Rituximab combined with tacrolimus induction + rituximab maintenance, Rituximab combined with tacrolimus induction + tacrolimus maintenance and Glucocorticoid combined with cyclophosphamide induction + maintenance in people with Efficacy and Safety, run by RenJi Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Qin Wang, doctor (+86136 2196 4604, qinwang_1975@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour urine protein quantification (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2022.