Iguratimod in Kidney Transplant Recipients

Study Overview
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Brief Summary
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The objective of the study is to evaluate the effect of iguratimod concomitant with conventional immunosuppressive drugs on preventing antibody-induced rejection in HLA Highly mismatched Kidney Transplant recipients.

Official Title
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An Open-label Study to Evaluate the Effect of Iguratimod Concomitant With Conventional Immunosuppressive Drugs on Preventing Antibody-induced Rejection in Human Leukocyte Antigen(HLA) Highly Mismatched Kidney Transplant Recipients

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: Iguratimod
* Drug: Mycophenolate mofetil
* Drug: Tacrolimus
* Drug: Glucocorticoids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged ≥18, <65 years At least 2 weeks post kidney transplantation from deceased or living donor Stable renal graft function, i.e., serum creatinine undulation for 3 consecutive test <±10% Serum creatinine<1.5×upper limits of normal(ULN) Number of HLA mismatches ≥ 4 Panel Reactive Antibody(PRA) value pre-transplantation <10% Concentration of conventional immunosuppressive drugs reach target ranges Subjects are willing to participate in the study, fully informed, and sign informed consent form(ICF) Women of childbearing potential (WOCBP) must have a negative pregnancy test within 24 hours prior to the start of study medication, and agree to use an acceptable method to avoid pregnancy for the entire study period and for up to 3 months after the last dose of study medication. Exclusion Criteria: Pregnant or nursing women Currently clinical acute rejection; Graft function hasn't recovered for delayed graft function (DGF), or primary non-function (PNF) Second or subsequent kidney transplant or multi-organ recipients (e.g. kidney and pancreas) Subjects with Liver failure Abnormal hepatic, renal and hematopoietic function, Alanine transaminase(ALT), Aspartate transaminase(AST)>1.5×ULN White blood cell(WBC)<3.5×10^9/L Hemoglobin(HGB)<80 g/L Platelet count(PLT)<80×10^9/L. Severe clinically relevant disease, Abnormality in chest X ray image, such as Tuberculosis, Pulmonary interstitial fibrosis, or symptom or physical sign of clinical significance Serious cardiovascular, hepatic, hematological, endocrinal disease, or malignancy 3）History of serious cardiovascular, hepatic, hematological, endocrinal disease, or malignancy 4) Immunodeficiency, uncontrolled active infection, and active gastrointestinal disease. Women or men of childbearing potential plan to be pregnant recently; Allergic with study drug, or excipient Subject with psychiatric illness, which may put him/her into unacceptable risk in the opinion of investigators Has received or is receiving Rituximab treatment Iguratimod treatment within 1 week pre-transplantation, or during screening period Received live vaccines in the previous 3 months, or plan to receive live vaccines during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experiment<br> | Drug: Iguratimod<br>* Subjects will receive iguratimod orally, twice a day, for consecutive 52 weeks<br>Drug: Mycophenolate mofetil<br>* All subjects will receive mycophenolate mofetil for consecutive 52 weeks<br>Drug: Tacrolimus<br>* All subjects will receive tacrolimus for consecutive 52 weeks<br>Drug: Glucocorticoids<br>* All subjects will receive glucocorticoids for consecutive 52 weeks<br>|
| Sham Comparator: Control<br> | Drug: Mycophenolate mofetil<br>* All subjects will receive mycophenolate mofetil for consecutive 52 weeks<br>Drug: Tacrolimus<br>* All subjects will receive tacrolimus for consecutive 52 weeks<br>Drug: Glucocorticoids<br>* All subjects will receive glucocorticoids for consecutive 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biopsy-proven acute rejection rates |  | 0-52 week | 
| Survival of transplanted kidney |  | 52 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Donor Specific Antibody(DSA) level compared to baseline |  | 52 week | 
| Graft renal function |  | 52 week | 
| Adverse event |  | 0-52 week |