Ensayos clínicos

Recipient Inclusion Criteria:

• Planned recipient of a first kidney allograft from an HLA-matched, living related donor. The donor and recipient must be HLA identical for both alleles at genetic loci HLA-A, HLA-B, and HLA-DRB1.
• Age ≥ 18 and ≤ 70 years at the time of providing informed consent.
• Single solid organ recipient (kidney only).
• ABO identical to the donor.  ABO compatible pairs that are not identical (e.g., ABO-O donor to ABO-A recipient) are not acceptable.
• Women of childbearing potential, including peri-menopausal women, should have a negative serum at Screening andor urine human chorionic gonadotropin (hCG) pregnancy test with a sensitivity < 50 mIU/mL at Screening and within 1 week prior to the kidney transplant surgery.  Women of childbearing potential, including peri-menopausal women, must receive contraceptive counseling and be willing and able to use effective contraception. The subject should use two chosen methods of contraception (e.g., hormonal contraceptives, intra-uterine device, diaphragm with spermicide, or condom with spermicide, male sterilization, or bilateral tubal occlusion) beginning no later than 4 weeks prior to starting MMF IS therapy, unless abstinence is the chosen method. She must be willing to continue contraceptive use during therapy and for at least 6 weeks after stopping MMF. In subjects for whom contraception is objectionable, complete abstinence (no vaginal penetration) for the duration of the study is required. Male subjects are required to use effective barrier contraception from Screening through at least 6 weeks after stopping MMF.   Able to receive oral medication.
• Able and willing to fully comply with all study procedures and restrictions.
• Acknowledgment of the expectation to participate in a separate, prospective, multi-year, longterm follow-up study (MDR-101-MLK-Plus) at the end of the current study (MDR-101-MLK).

Recipient Exclusion Criteria:

• Underlying kidney disease with a high risk of disease recurrence in the transplanted kidney, including:
  • Focal segmental glomerulosclerosis (FSGS);
  • Type I or II membranoproliferative glomerulonephritis;
  • Hemolytic-uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP).
• History of clinically important genitourinary tract dysfunction.
• History of undergoing a prior hematopoietic cell transplant, organ transplant, any cell therapy, or any gene therapy.
• Baseline positive donor-specific anti-HLA antibody testing (DSA).
• History of HUS, atypical HUS, or TTP.
• Women who are pregnant or breastfeeding.
• Is taking IS therapy [eg, glucocorticoids, cyclosporine, mycophenolate, tumor necrosis factor (TNF) inhibitors] for multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, or other acute or chronic condition.
• History of prior treatment with rabbit-derived ATG or a known allergy to rabbit proteins.
• History of cancer with the exception of non-melanoma skin cancer and adequately treated breast, prostate, or cervical in situ lesions (i.e., locally confined, non-invasive tumors) within 5 years prior to Screening.
• Has an active serious infection not controlled by oral or IV antibiotics or antifungals.
• Leukopenia (WBC count < 3,000/μL) or thrombocytopenia (platelet count < 100,000/μL).
• Serological or nucleic acid test (NAT) evidence of human immunodeficiency virus (HIV)-1 or HIV-2.
• Evidence of prior hepatitis B (HBV) infection as evaluated by hepatitis B surface antigen (HBsAg), total hepatitis B core antibody [(anti-HBc Immunoglobulin M (IgM) and Immunoglobulin G (IgG)] and hepatitis B surface antibody (anti-HBsAb), or exhibiting a positive HBV polymerase chain reaction (PCR) result.
• Evidence of prior hepatitis C (HCV) infection as evaluated by positive anti-HCV antibodies and a positive serum HCV ribonucleic acid (RNA) PCR. Participants with positive HCV antibodies but undetectable serum HCV RNA may be considered for eligibility. Participants with negative anti-HCV antibodies but unexplained liver enzyme abnormalities must undergo a quantitative serum RNA assay to rule out false negative HCV serologies.  Known hypersensitivity to dimethyl sulfoxide (DMSO), dextran, murine (mouse) proteins, or iron dextran.
• Has any medical condition or any circumstance that in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities, or would significantly interfere with the subject’s protocol compliance or put the subject at increased risk.
• Has been exposed to a live vaccine, approved or investigational, within the 30 days prior to the scheduled kidney transplantation.
• Participation in any other study of an investigational device, small molecule medication, biologic medication, or other agent within 30 days or 5 half-lives of the investigational product, whichever is longer, before MDR-101-MLK study enrollment and until completion of the final study followup visit.

Donor Inclusion Criteria:

• HLA-matched first-degree (parent, child or sibling) or second-degree (child of a sibling, half sibling) relative of the prospective recipient participant. The donor and recipient must be HLA identical for both alleles at genetic loci HLA-A, HLA-B, and HLA-DRB1.
• Age ≥ 18 and ≤ 7065 years at the time of providing informed consent.
• Prepared to be a living related kidney donor, and capable, as defined below, of undergoing G-CSF mobilization and apheresis for donation of hematopoietic cells:
  • Weight ≥ 50 kg, hematocrit ≥ 38%, and platelet count ≥ 110,000/μL;
  • Adequate peripheral venous access for apheresis. A central venous catheter may be placed with appropriate informed consent from the prospective donor.
• Women of childbearing potential, including peri-menopausal women, should have a negative serum at Screening andor urine human chorionic gonadotropin (hCG) pregnancy test with a sensitivity < 50 mIU/mL at Screening and within 1 week prior to the kidney transplant surgery.
• Able and willing to fully comply with all study procedures and restrictions.
• Meets institutional selection criteria for kidney donation and apheresis of mobilized peripheral blood stem cells (PBSCs).
• Able to understand and provide written, signed, and dated informed consent to participate in the study.

Donor Exclusion Criteria:

• Known sensitivity to filgrastim or to E. coli-derived recombinant protein products.
• History of autoimmune disorders, including rheumatic diseases and unsuccessfully treated thyroid disorders.
• History of undergoing a prior hematopoietic cell transplant, organ transplant, any cell therapy, or any gene therapy.
• History of type 1 or type 2 diabetes mellitus.
• History of blood product donation to prospective recipient participant.
• Pregnant or breastfeeding.
• History of deep vein thrombosis or pulmonary embolism.
• History of iritis or episcleritis.
• Current treatment with lithium.
• Taking IS therapy (e.g., glucocorticoids, CsA, Tac, mycophenolate, or TNF inhibitors).
• Positive Hemoglobin-Solubility (e.g., SickleDex™ or equivalent) test.
• Tests confirmed positive for HIV-1/2, human T-cell lymphotropic virus (HTLV)-I/II, West Nile Virus, HBV (as evaluated by HBsAG, anti-HBcIgM and IgG, and anti-HBsAg, or exhibiting a positive HBV PCR result), HCV (as evaluated by positive anti-HCV antibodies and a positive serum HCV RNA PCR; positive HCV antibodies but undetectable serum HCV RNA may be considered for eligibility), T. cruzi, or syphilis. Cytomegalovirus (CMV)-positive donors will not be excluded but the subject and Investigator will be notified of the CMV-positive status.  Epstein-Barr Virus (EBV)-positive donors will be excluded if the prospective transplant recipient is EBV naive.
• History of infection with Zika virus (ZIKV) in the past 6 months, as evidenced by a clinical diagnosis and/or a positive test for ZIKV. Each transplant center may use local screeening practices to screen and exclude donors with geographic (residence/travel) risk for ZIKV in the donor or the donor’s sexual partner(s).
• History of myeloid leukemia, myeloproliferative disease (e.g., polycythemia vera, essential thrombocythemia, myelofibrosis), or prior hematopoietic cell transplant.
• Participation in any other study of an investigational device, small molecule medication, biologic medication, or other agent within the 30 days or 5 half-lives of the investigational product, whichever is longer, before MDR-101-MLK study enrollment and until completion of the final donor study follow-up visit.
• Has any condition or circumstance, which in the opinion of the Investigator would significantly interfere with the subject’s protocol compliance or put the subject at increased risk.