Trial to Evaluate Safety and Tolerability of Tacrolimus Extended-Release (Astagraf XL) in Human Leukocyte Antigen (HLA) Sensitized Kidney Transplant Recipients
Condition: End Stage Renal Disease
MeSH terms: Kidney Failure, Chronic
Intervention: Tacrolimus Extended-Release Oral Capsule
Intervention description: Maintenance immunosuppression will consist of tacrolimus extended-release, mycophenolate mofetil 500mg twice daily or mycophenolate sodium 360mg twice daily, and prednisone.
Intervention MeSH terms: Tacrolimus
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Highly-sensitized; Kidney transplantation; Desensitization

Summary:

      The purpose of this study is to demonstrate the safety of tacrolimus extended-release in HLA
      sensitized (HS, defined as panel reactive antibody ≥ 30%), kidney transplant recipients after
      desensitization with intravenous immunoglobulin (IVIG) and rituximab (also known as ritux)
      +/- plasma exchange (PLEX) per the standard of care with alemtuzumab induction.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Recipient of a deceased or living donor kidney allograft

          2. Patients must have undergone desensitization with intravenous immunoglobulin (IVIG)
             and rituximab with or without plasma exchange prior to transplant or be administered
             IVIG and rituximab peri-operatively (within seven days of transplant) post-transplant

          3. Age 18 and over

          4. Able to understand and provide informed consent

          5. Calculated Panel Reactive Antibodies (CPRA)> 30% demonstrated on 3 consecutive
             samples. The methodology to measure polymerase chain reaction (PCR) includes FLOW and
             Luminex Single Antigen Assay.

          6. At transplant, patient must have an acceptable crossmatch (as defined as T-or B- Flow
             Cytometry Crossmatch (FCMX) ≤ 225 MCS) from non-HLA identical donor. Negative
             crossmatch is Tpronase FCMX <70; T- FCMX <50 and Bpronase FCMX <130; B-FCMX <100.

        Exclusion Criteria:

          1. Recipients of a dual simultaneous kidney/liver, kidney/heart, kidney/lung, or
             kidney/pancreas transplant

          2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical
             classes

          3. Patients being treated with drugs that are strong inducers or inhibitors of cytochrome
             P450 3A4

          4. Patients with a clinically significant systemic infection within 30 days prior to
             transplant

          5. Patients who have any surgical or medical condition that may affect absorption of
             drug, such as severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes
             mellitus, which in the opinion of the investigator, might significantly alter the
             absorption, distribution, metabolism and/or excretion of study medication

          6. Women of childbearing potential who are either pregnant, lactating, planning to become
             pregnant during this trial, or with a positive serum or urine pregnancy test. Women of
             childbearing potential must be willing to agree to contraceptive practices.

          7. Patients who are PCR positive for Hep B, Hep C, or HIV.