A Multicenter Clinical Trial: Risk Factors of Chinese Kidney Transplant Recipients DSA Based on MPA Immunosuppressive Regimen

Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University

THE INCIDENCE AND INFLUENTIAL FACTORS OF DSA IN CHINESE RENAL TRANSPLANT RECIPIENTS WITH MPA-BASED IMMUNOSUPPRESSIVE REGIMEN： A MULTI-CENTER CLINICAL STUDY (TIAIFOD STUDY)

Study procedure Investigators at participating centers will identify patients fulfilling inclusion criteria and do not violate any exclusion criteria. Informed consent will be obtained upon entry into the study according to national regulations. Patients will be enrolled into the study and clinical data of patient history will be collected. Clinical data will be collected prospectively up to a total period of 12 months.

Medical history and Kidney transplantation This will include age at transplantation, gender, race, weight, height of both recipient and donor; Recipients: previous history ,BMI ,primary kidney disease including biopsy proven diagnosis (if present), historic dialysis，pregnancy history (female). Donor: the catalogue (DCD,DBD,DBCD), ECD or not，the cause of death, received CPR or not; zero biopsy results if done, ABO blood type match, HLA-MM, cold and warm ischemic time.

Clinical data at baseline and 12months follow up period:

Clinical assessments, laboratory, comorbidity, immunosuppressive therapy, and selected concomitant therapy (anti-hypertension anti-hyperlipidemics, anti-diabetics and drugs known to affect renal function) will be collected at transplant day（Day 0, visit 0）and 8 subsequent visits scheduled Day 3, Week1, Week2, Week 4，Week 12，Week 26，Week 40，Week 52 post transplantation. MPA-AUC, acute rejection episodes and graft loss will be collected at visits scheduled Day 3, Week 1，Week 2, Week 4，Week 12， Week 26(6 month)，Week 40，Week 52 (12 month) post transplantation. On day 3, MPA-AUC will be tested by full time sample (0h,0.5h,1h,2h,3h,4h,6h,8h,10h,12h post receiving MMF). LSS (0h, 0.5h, 2h post receiving MMF) will be used for testing MPA-AUC on other visits. PRA will be tested on week 4, week 12, week 26, week 52. If PRA is positive, DSA will be tested following once. All the PRA and DSA MFI and phenotype will be collected（including the clinical-drive test）.

Statistical analysis:

The primary endpoint in this study is the incidence of DSA formation in 12-months post-transplantation in Chinese kidney transplant recipients with MMF-based IS regimen. The proportion and its 95% CI will be provided.

The influential factors of DSA formation will be estimated using logistic regression including relevant influential factors, where the influential factors are defined as {age, gender of donor / recipients recipient: BMI, blood transfusion, previous AR （before DSA appears）, ECD , cold ischemia time, HLA-MM, Tac trough concentration, MPA-AUC, DGF, introduction therapy (including use or not and the drugs )}. .

The full MPA-AUC0-12h will be calculated using the trapezoidal rule. The calculated formula with Limited Sample Strategy (LSS) will be established to predict the MPA-AUC0-12h in the Chinese patients. Correlation coefficients will be calculated and multiple stepwise regression analysis will be used to determine the time points and best equation for evaluating MPA-AUC0-12h.

Estimates for the time-to-event variable(s), such as Overall Survival(OS), will be obtained by using the Kaplan-Meier (KM) approach together with associated 95% CI.

The other secondary endpoints will be summarized descriptively depended on the variable type. The comparison between patients with and without DSA-positive will be performed according to the variable type.

• Kidney Transplant Recipients

Intervention type: Drug

Intervention name: Mycophenolate Mofetil Capsules

Description: Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation

Arm group label: Mycophenolate Mofetil Capsules

Other name: Other MPAs

Criteria:

Inclusion Criteria:

- Male or female kidney transplant recipients from 18 to 65 years of age (including 18 & 65 years old patients)

- Single organ and first kidney transplant recipients from donation after citizen's death

- Patients who received MMF+TAC+ Corticosteroids immunosuppressive regimen as first choice post transplantation

- Pre-transplant PRA is negative (0%)

- One serum pregnancy test with a sensitivity of at least 25mlU/Ml for patients of childbearing potential before enrolled. A second test should be performed 8-10 days later. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. Patients should be instructed to consult their physician immediately should pregnancy occur. For patients to be included in the study, negative result must be obtained. And highly effective contraception for women of childbearing potential. Contraception must be taken before beginning study drug therapy, during therapy and for 6 weeks after the last dose of study medication

Exclusion criteria:

- Patients who do not receive MMF

- Patients who are re-transplantation or multiple organ transplantation recipients

- Female patients who are pregnant or lactating

- Patients who have any form of substance abuse, psychological illness or any other condition, which, in the opinion of the investigator, may interfere with the patient's ability to understand the requirements of the study.

- Patients who would have received another investigational drug within 30 days preceding the enrollment, received prohibited immunosuppressant medications prior to transplant

- Patients who are using AZA, MTX, CTX or will use these drugs post-transplantation

- Known contraindications to TAC , corticosteroids, MMF

- Patients who have active peptic ulcer

- Patients who have severe cardiac or lung disease

- Patient who have active hepatica disease

- Patients who have a history of cancer, except successfully treated localized nonmelanocytic skin cancer

- Patients who would not be available for routine study visits or follow-up, or not being followed by an accredited laboratory.

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: No

Last name: Wujun Xue, Prof.

Phone: +86 13991990128

Email: [email protected]

January 2020

Responsible party type: Sponsor

• kidney transplant recipients
• Mycophenolate Mofetil Capsules
• Acute Rejection
• Cyclosporine
• Delayed graft function
• Tacrolimus
• Mycophenolic Acid Area under the Curve

Arm group label: Mycophenolate Mofetil Capsules

Arm group type: Other

Description: The dosage of mycophenolate mofetil (CellCept) will be decided by the investigator and should be adjusted according to clinical response or therapeutic drug monitoring. It is not allowed to switch to other MPAs. When MMF is discontinued but is not switched to other MPA, the patients will be followed until the end of study.

Allocation: N/A

Intervention model: Single Group Assignment

Intervention model description: To estimate the incidence of DSA formation during 12-months post-transplantation

Primary purpose: Treatment

Masking: None (Open Label)