MURINE OKT4A IMMUNOSUPPRESSION IN CADAVER DONOR RENAL-ALLOGRAFT RECIPIENTS - A COOPERATIVE CLINICAL-TRIALS IN TRANSPLANTATION PILOT-STUDY

Background. A phase I study of anti-CD4 immunosuppression of cadaver d onor renal allograft recipients was conducted by the NIH Cooperative C linical Trials in Transplantation to assess safety, tolerability, immu noactivity, and pharmacokinetics of multiple infusions of murine anti- human CD4 monoclonal antibody OKT4A. Methods. Thirty patients were enr olled (from August 1992 to October 1993) and received OKT4A at doses o f 0.5 mg/kg (24 patients), 1.0 mg/kg (three patients), and 2.0 mg/kg ( three patients) beginning and continuing for 12 consecutive days with a standard regimen of cyclosporine, azathioprine, and prednisone. OKT4 A treatment was continued postoperatively if serum creatinine 24 hr af ter transplantation was <85% of pre-transplantation baseline creatinin e. Results. Ninety-three percent of patients treated at 0.5 mg/kg OKT4 A and all patients at higher doses had mean peak CD4 saturations in ex cess of 90%. A human antimouse antibody response of more than three ti mes pretreatment levels was observed in 84% of patients. There was no evidence of CD4 T-cell depletion. OKT4A was well tolerated without fir st-dose side effects. For the 19 eligible patients treated with 0.5 mg /kg OKT4A with initial graft function, the 3-month treated rejection r ate was 37%. The 2-year graft survival rate for all 30 patients enroll ed was 83%, and for the 19 eligible patients it was 95%. Conclusions. The high percentage of CD4 saturation, minimal side effects, the obser vation of a low 3-month rejection rate, and an excellent 2-year graft survival rate in patients treated with 0.5 mg/kg OKT4A support the con tinued investigation of an anti-CD4 approach to immunosuppressive ther apy.