renal transplantation MedDRA version: 21.1 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865
Conditions
Sponsors
ITB-MED AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able to understand the study requirements and provide written informed consent before any study assessment is performed. 2. Male or female patients = 18 to 70 years of age. 3. Recipients of a de novo renal allograft from a heart-beating deceased, living unrelated or non-HLA identical living related donor. 4. Recipients of a kidney with a cold ischemia time (CIT) =65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: • Transplant recipients sero-negative for Epstein-Barr virus (EBV). • Multi-organ transplant recipients. • Subjects who have received a kidney allograft previously; e.g. re-transplant. • Recipient of a kidney from an HLA identical living related donor. • Recipient of a kidney from a donor after cardiac death. • Subjects at high immunological risk for rejection as determined by local practice [(e.g., presence of pre-existing DSA, recipient of high Kidney Donor Profile Index = 85 kidney (where assessed)]. • Subjects with donor specific anti-HLA antibody as measured by complement-dependent cytotoxicity assay (CDC), enzyme-linked immunosorbent assay (ELISA), or flow cytometry within 90 days prior to transplant or as performed per the center’s local practice. • Complement-dependent cytotoxicity (CDC) crossmatch positive transplant (isolated positive B cell crossmatches are not an exclusion criterion). • ABO incompatible recipient. • History of malignancy of any organ system, except for localized excised non-melanomatous skin lesions or carcinoma in situ of the cervix. • Subjects with clinically significant laboratory abnormality that would preclude participation in the study (e.g., >2.5 x Upper Limit of Normal (ULN) values for (a) liver function chemistries (ALT, AST, alkaline phosphatase (ALP)), (b) bilirubin, (c) coagulation studies (INR/PT, aPTT). • Patient with any of the following: hemoglobin (Hbg) < 8 mg/dL, WBC count = 2,000/mm3 or platelet count = 75,000/mm3. • Sero-positive for Human Immunodeficiency Virus (HIV) or Hepatitis B Surface Antigen (HBsAg). Subjects who are sero-positive for Hepatitis C virus (HCV) are excluded without proof of sustained viral response (SVR) after anti-HCV treatment. • Recipient of a kidney from a donor who tests positive for HIV, HBsAg/HBc positive or HCV. • History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes (e.g., siplizumab, ATG, TAC, MMF, CS). • Any additional contraindication to the use of TAC or MMF according to the national labeling information of these products (refer to the local product label). • Evidence of TB infection (after anti-TB treatment, patients with history of latent TB may become eligible according to national guidelines). • Patient with severe systemic infections, current or within the two weeks prior to randomization. • Subjects with any other clinically significant medical condition, active infection or laboratory abnormality that would, in the judgment of the investigator, interfere with the subject’s ability to participate in the study. • Subjects who, in the opinion of the investigator, are not capable of giving informed consent for the study or who are unable or unwilling to adhere to the study requirements outlined in the protocol. • Use of other investigational products or enrollment in another investigational drug study within 30 days of screening or 5 half-lives of the medication, whichever is longer. • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. • Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 24 weeks after the study medications have been stopped.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety, tolerability, PK and PD of siplizumab compared to rATG, in de novo renal transplant recipients at 12 months post-transplant.;Secondary Objective: • To measure changes in peripheral lymphocyte immunophenotype • To the time-course and duration of siplizumab induced lymphocyte depletion and time to recovery • To measure peripheral CD2-receptor occupancy following siplizumab administration over time • To assess the incidence of treated biopsy proven acute rejection (tBPAR) at 12 months • To assess the incidence of treatment emergent de novo, donor specific antibodies (DSA) at 12 months • To assess the incidence of antibody meditated rejection at 12 months • To assess renal function via eGFR using MDRD equation at Months 3, 6, 12 or EOS;Primary end point(s): • Adverse events • Serious adverse events • Clinically significant changes in clinical chemistry, hematology, vital signs, serology • siplizumab PK • Immunophenotyping • CD2 RO • eGFR via MDRD;Timepoint(s) of evaluation of this end point: 12-months post-transplant | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Immunophenotyping via FACS • Lymphocyte counts • CD2 RO • Anti-siplizumab Ab • Incidence of BPAR • de novo-DSA / anti-HLA ab measurement • incidence of AMR;Timepoint(s) of evaluation of this end point: 12-months post-transplant | — |
Countries
Austria, Spain, Sweden
Contacts
Public ContactClinical Trial Information
ITB-MED LLC
Outcome results
None listed