Tocilizumab for Renal Graft Inflammation
Condition: Late Complication From Kidney Transplant
MeSH terms: Inflammation
Intervention: Tocilizumab
Intervention description: Will receive tocilizumab 8 mg/kg intravenously at four-week intervals for a total of 6 doses. In addition, will continue usual immunosuppressive regimen.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Kidney transplantation; Inflammation

Summary:

      Randomized open label clinical trial in which 48 renal transplant recipients with
      inflammation in the 6 month allograft biopsy will either continue usual immunosuppression or
      receive monthly Actemra (Tocilizumab) infusions for 6 months in addition to usual
      immunosuppression.
    

Eligibility criteria:

        Inclusion Criteria:

          -  All kidney transplant recipients with SCI on 6-month surveillance biopsy.

          -  Maintenance immunosuppression regimens containing tacrolimus and MMF with or without
             prednisone.

          -  Ability to provide written informed consent for the study.

          -  Men and women of reproductive potential must agree to use an acceptable method of
             birth control during treatment and for six months after completion of treatment.

        Exclusion Criteria:

        General:

        • Major surgery (including joint surgery) within 8 weeks prior to screening or planned
        major surgery within 6 months following randomization.

        Excluded Previous or Concomitant Therapy:

          -  Treatment with any investigational agent within 4 weeks (or 5 half-lives of the
             investigational drug, whichever is longer) of screening.

          -  Previous treatment with any cell-depleting therapies, including investigational agents
             or approved therapies, some examples are CAMPATH, anti-CD4, anti-CD5, anti-CD3,
             anti-CD19 and anti-CD20, except Thymoglobulin.

          -  Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6
             months of baseline.

          -  Immunization with a live/attenuated vaccine within 4 weeks prior to baseline.

          -  Previous treatment with TCZ (an exception to this criterion may be granted for single
             dose exposure upon application to the sponsor on a case-by-case basis).

          -  Any previous treatment with alkylating agents such as chlorambucil, or with total
             lymphoid irradiation.

        Exclusions for General Safety:

          -  Presence of acute cellular (Banff Type 1-3) or antibody-mediated rejection on 6-month
             surveillance biopsy or on biopsies for-cause in the previous 6 months.

          -  History of positive urine or serum screening for BK virus (defined as a quantitative
             BK virus PCR in urine > 0.5 million copies/ml or any detectable BK viremia) within the
             first 6 months post-transplant.

          -  History of severe allergic or anaphylactic reactions to human, humanized or murine
             monoclonal antibodies.

          -  Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary
             (including obstructive pulmonary disease), renal, hepatic, endocrine (include
             uncontrolled diabetes mellitus) or gastrointestinal disease (including diverticulitis,
             ulcerative colitis, or Crohn's disease.)

          -  Current liver disease as determined by principal investigator unless related to
             primary disease under investigation.

          -  Known active current or history of recurrent bacterial, viral, fungal, mycobacterial
             or other infections (including but not limited to tuberculosis and atypical
             mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding fungal
             infections of nail beds).

          -  Any major episode of infection requiring hospitalization or treatment with IV
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
             screening.

          -  Active TB requiring treatment within the previous 3 years. Patients should be screened
             for latent TB and, if positive, treated following local practice guidelines prior to
             initiating TCZ. Patients treated for tuberculosis with no recurrence in 3 years are
             permitted. (Appendix 8).

          -  Primary or secondary immunodeficiency (history of or currently active) unless related
             to primary disease under investigation.

          -  Evidence of active malignant disease, malignancies diagnosed within the previous 10
             years (including hematological malignancies and solid tumors, except basal and
             squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has
             been excised and cured), or breast cancer diagnosed within the previous 20 years
             unless related to primary disease under investigation.

          -  Pregnant women or nursing (breast feeding) mothers.

          -  Patients with reproductive potential not willing to use an effective method of
             contraception.

          -  History of alcohol, drug or chemical abuse within 1 year prior to screening.

          -  Patients with lack of peripheral venous access.

        Laboratory Exclusion criteria (at screening):

          -  Serum creatinine > 1.6 mg/dL (141 µmol/L) in female patients and > 1.9 mg/dL (168
             µmol/L) in male patients. Patients with serum creatinine values exceeding limits may
             be eligible for the study if their estimated glomerular filtration rates (GFR) are >30
             ml/min/1.73 m2.

          -  Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 times upper
             limit of normal (ULN)

          -  Total Bilirubin > 1.5 times ULN

          -  Platelet count < 100 x 109/L (100,000/mm3)

          -  Hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L)

          -  White Blood Cells < 3.0 x 109/L (3000/mm3)

          -  Absolute Neutrophil Count < 2.0 x 109/L (2000/mm3)

          -  Absolute Lymphocyte Count < 0.5 x 109/L (500/mm3)

          -  Positive Hepatitis BsAg, or Hepatitis C antibody