Tocilizumab for Renal Graft Inflammation

• Status: Completed
• Trial end date: 2018-12-16
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Flavio Vincenti; University of California, San Francisco

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