Efficacy and Safety of Tacrolimus in Combination With Ripertamab in the Initial Treatment of Patients With MCD

Efficacy and Safety of Tacrolimus in Combination With Anti-CD20 Monoclonal Antibody (Ripertamab) in the Initial Treatment of Patients With Minimal Change Disease: a Multi-center Randomized Controlled Clinical Trial

To evaluate the safety and efficacy of ripertamab and its combination with tacrolimus in the initial treatment of MCD to provide a treatment regimen with higher remission rates, lower recurrence rates, and fewer side effects in patients with MCD.

Study Overview

• Status: Not yet recruiting
• Conditions: Minimal Change Disease
• Intervention / Treatment: Drug: Supportive care+Prednisone; Drug: Supportive care+Tacrolimus+Ripertamab; Drug: Supportive care+Ripertamab

Detailed Description

Minimal change disease is the third most common primary kidney disease in adults with idiopathic nephrotic syndrome. The pathological features of the disease are no or only slight changes under light microscope, and the foot process fusion under electron microscope. The KDIGO guidelines recommend oral adequate doses of glucocorticoids as the initial treatment for adults with MCD. However, 48%-76% of patients relapse after tapering or gradual discontinuation of the drug, requiring a high cumulative dose of glucocorticoids. As the cumulative dose of glucocorticoids increases, the potential for side effects increases. In addition, 10% to 30% of patients frequently relapse, and 15% to 30% of these are steroid dependent. Therefore, the clinical goals for patients with MCD are to achieve early remission of proteinuria, reduce hormonal side effects, and more importantly, prevent the recurrence of proteinuria.

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: shiren Sun[Author], Doctor; Phone Number: 18729387675; Email: 272844142@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18-80 years old;
2. Primary minimal change disease confirmed by renal biopsy (Initial therapy);
3. 24h-UTP>3.5g/d or PCR>3500mg/g, and serum albumin<30g/L;
4. Agree to participate in the project and sign the informed consent.

Exclusion Criteria:

1. Secondary minimal change disease;
2. eGFR<60 mL/min/1.73m2;
3. Had history of mental disease, dysnoesia, serious cardiovascular and cerebrovascular diseases, pulmonary insufficiency, malignant tumors or other major diseases that are not suitable for clinical experiments;
4. Active bleeding in the gastrointestinal tract;
5. Prior treatment with corticosteroids or other immunosuppressants;
6. HBV, HCV, HIV or other untreated infections, congenital or acquired immunodeficiency diseases;
7. Have been vaccinated with live vaccine in the past four weeks;
8. Serum bilirubin > 3.6mg/dl for at least 1 month or liver function ≥3 times the upper limit of normal value;
9. Allergic to prednisolone, tacrolimus, or ripertamab;
10. Reluctance to use contraception or plan pregnancy/lactation within 6 months of study completion;
11. Had history of alcohol/drug abuse;
12. Unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Group; Supportive care+Prednisolone	Drug: Supportive care+Prednisone; Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Induction period: 1mg/kg/day. The maximum dose is not more than 60mg. The duration of adequate prednisone is a minimum of 4 weeks and a maximum of 16 weeks. Maintenance period: A reduction of 5-10mg/wk was initiated after 2 weeks of complete remission and finally discontinued after 6 months of maintenance at 5mg/day.; Other Names: Control group
Active Comparator: Test group 1; Supportive care+Tacrolimus+Ripertamab	Drug: Supportive care+Tacrolimus+Ripertamab; Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Tacrolimus：Induction period: 0.05mg/kg/d. It will be given in two doses 12 hours apart. The blood concentration should be up to 5-10ng/ml. Maintenance therapy was initiated two weeks after complete remission; Maintenance period: Reduced to a blood concentration of 3-8ng/ml, and stopped after 6 months of maintenance treatment. Ripertamab: Given twice every two weeks at a dose of 1000mg. 1000mg is added at 6 months.; Other Names: Test group 1
Active Comparator: Test group 2; Supportive care+Ripertamab	Drug: Supportive care+Ripertamab; Supportive care: Control blood pressure:ACEI/ARB; Diet that is low in fat and salt; Stop smoking; Moderate exercise. Ripertamab: Given twice every two weeks at a dose of 1000mg. 1000mg is added at 6 months.; Other Names: Test group 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse rate at 24 months	Relapse: Proteinuria>3.5g/d or PCR>3500mg/g after complete remission has been achieved.	Up to 24 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse rate at 12/18 months	The relapse rates of MCD patients at 12 months and 18 months were observed	Up to 18 months after enrollment
Partial or complete remission at 2/6/12/24 months	Partial remission: Reduction of proteinuria to 0.3-3.5g/d, or PCR 300-3500mg/g and a decrease >50% from baseline Complete remission: Reduction of proteinuria to <0.3g/d or PCR<300mg/g	Up to 24 months after enrollment
The time from the start of treatment to achieve complete remission	The time it takes for patients with MCD to reach a state of complete remission needs to be observed	Up to 24 months after enrollment
The time from clinical complete remission to replase		Up to 24 months after enrollment
Safety-adverse events	Creatinine levels doubled from baseline; an increase ≥30% from eGFR baseline; ESRD; adverse events; drug-related adverse events, and abnormal clinical manifestations	The time from randomization until the occurrence of such adverse events, up to 24 months

Collaborators and Investigators

• Sponsor: Air Force Military Medical University, China
• Collaborators: First Affiliated Hospital Xi'an Jiaotong University; Shaanxi Provincial People's Hospital; Second Affiliated Hospital of Xi'an Jiaotong University; The Second Affiliated Hospital of Air Force Military Medical University; Shaanxi Provincial Hospital of Chinese Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: May 4, 2024
• First Submitted That Met QC Criteria: May 4, 2024
• First Posted (Actual): May 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Nephrosis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephrosis, Lipoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Calcineurin Inhibitors; Prednisone; Tacrolimus
• Other Study ID Numbers: TAC and ripertamab in MCD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No