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

Minimal Change Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06405100
• Other study ID #: TAC and ripertamab in MCD
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: May 2024
• Est. completion date: April 2027

Study information

• Verified date: April 2024
• Source: Air Force Military Medical University, China
• Contact: shiren Sun[Author], Doctor
• Phone: 18729387675
• Email: 272844142[@]qq.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 81
• Est. completion date: April 2027
• Est. primary completion date: April 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Minimal Change Disease
• Nephrosis, Lipoid

Intervention

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.
• 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.
• 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.

Locations

Country	Name	City	State
n/a

Sponsors (6)

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	The time from clinical complete remission to replase		Up to 24 months after enrollment
Secondary	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