An Open Study on the Preventive Effect of Early Mizoribine Conversion on BKV Nephropathy in Renal Transplant Recipients

This study is divided into two parts: ① Part I was a retrospective observational study. Kidney transplant recipients infected with BK virus (BKV) in the First Affiliated Hospital of Sun Yat-sen University from 2015 to 2021 were retrospectively collected and divided into case group and control group whether to convert MPA drug to mizoribine. ② The second part was a prospective, open and interventional clinical trial. Thirty patients with positive urinary BK virus after kidney transplantation using Mycophenolic acid (MPA) were enrolled in the First Affiliated Hospital of Sun Yat-sen University. All patients who met the inclusion criteria were treated with mizoribine to place MPA (Mycophenolate or mycophenolate sodium enteric coated tablets) for 12 months as directed. At the baseline of follow-up (before enrollment) and at each follow-up point, clinical indicators of patients were recorded, and renal biopsy was performed to evaluate the occurrence of BKV nephropathy in patients with persistent elevated BK viruria or persistent BK viremia after conversion and patients with BK viruria after 12 months, and to judge the progress after early activation of BKV and the safety of mizoribine.

Study Overview

• Status: Not yet recruiting
• Conditions: BK Virus; Kidney Transplant Recipients
• Intervention / Treatment: Drug: Mizoribine

Detailed Description

This study is divided into two parts: ① Part I was a retrospective observational study. Kidney transplant recipients infected with BK virus (BKV) in the First Affiliated Hospital of Sun Yat-sen University from 2015 to 2021 were retrospectively collected and divided into case group and control group whether to convert MPA drug to mizoribine. The basic data of the two groups, the concentration of mizoribine, the clinical benefit after conversion and the outcome of BKV infection were analyzed, and the clinical improvement rate and preliminary safety of mizoribine conversion on BKV infection were determined. ② The second part was a prospective, open and interventional clinical trial. Thirty patients with positive urinary BK virus after kidney transplantation using Mycophenolic acid (MPA) were enrolled in the First Affiliated Hospital of Sun Yat-sen University. The patients and their families voluntarily participated in the experiment and signed the Informed Consent on the premise of fully understanding the treatment plan. The treatment was approved by the hospital ethics Committee. All patients who met the inclusion criteria were treated with MPA (Mycophenolate or mycophenolate sodium enteric coated tablets) replaced with mizoribine for 12 months. At the baseline of follow-up (before enrollment) and at each follow-up point, clinical indicators of patients were recorded, and renal biopsy was performed to evaluate the occurrence of BKV nephropathy in patients with persistent elevated BK viruria or persistent BK viremia after conversion and patients with BK viruria after 12 months, and to judge the progress after early activation of BKV and the safety of mizoribine.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yang huan; Phone Number: 15626450204; Email: huan.yang@leespharm.com

Study Locations

• China
  • Guangzhou, China
    • The First Affiliated Hospital of Sun Yat-sen University
    • Contact: huan Yang; Phone Number: 15626450204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Kidney transplant recipients;
• Postoperative maintenance therapy with glucocorticoid + tacrolimus +MPA;
• Urinary BKV-DNA load ≥10^7/L;
• No gender limitation for recipients > 18 years of age;
• Voluntarily sign written informed consent.

Exclusion Criteria:

• Multiple organ transplantation;
• Acute rejection occurred within 1 week before enrollment;
• Recipients with signs of active infection;
• Recipients with white blood cell count below 3,000 /cubic metre;
• Women who are pregnant, breast-feeding, or unwilling to use appropriate contraceptive methods during the study period;
• Patients with serious gastrointestinal diseases and active peptic ulcer disease;
• Suffering from any mental illness;
• Patients with severe heart disease and abnormal cardiac function;
• Subjects with known allergy to the test drug;
• Other competent physicians judged that the recipients were not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants who had BKV-related nephropathy occurred	During the follow-up, patients with urinary BKV-DNA increase of more than 10 times for 3 consecutive months after dressing change, or viremia (serum BKV-DNA load ≥10^4/ mL) for 3 consecutive months after dressing change, as well as patients with urinary BKV positive 12 months after dressing change, were evaluated by renal biopsy pathology. The number of Participants who had BKV-related nephropathy occurred will be counted.（BKV stands for BK polyoma virus）	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants in who Serum and urine BK viral load were cleared	During the observation period, the presence of serum BKV and the corresponding BKV-DNA load of the subjects were recorded to determine the incidence and outcome of BKV.	12 month
Number of Participants with Acute rejection	Diagnosis of acute rejection: including clinical diagnosis and pathological diagnosis. If the serum creatinine increased by more than 20% within 72 hours, acute rejection was suspected, and ultrasound examination of the transplanted kidney was performed, and biopsy of the transplanted kidney was performed if necessary. Acute rejection (BPAR) confirmed by biopsy needs to be diagnosed by a pathologist according to the classification criteria (1997 edition and subsequently updated). If not confirmed by biopsy, acute rejection should be diagnosed based on the exclusion of other causes of elevated creatinine.	12 month
Number of Participants with Renal graft loss	During the study, renal function was recorded, the survival of transplanted kidneys was counted and the survival rate of transplanted kidneys was calculated.	12 month

Collaborators and Investigators

• Sponsor: Lee's Pharmaceutical Limited

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): May 1, 2024

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Mizoribine
• Other Study ID Numbers: BLDN-LEES-2022-3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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