a randomized, phase i/ii trial to assess the safety and antiviral effects of escalating doses of a human anti-cytomegalovirus monoclonal antibody (sdz msl-109) in patients with the acquired immunodeficiency syndrome and cmv viremia and/or viruria

Conditions: Cytomegalovirus Infections; HIV Infections

Summary: to determine the safety, tolerance, and potential in vivo antiviral effects of five dosage levels and a dose to be determined of human anti-cytomegalovirus (cmv) monoclonal antibody (sdz msl-109; formerly sdz 89-109) when administered once every 2 weeks for a total of 12 doses to patients with either aids or eligible aids-related complex (arc) and with culture proven evidence of cmv viremia and/or viruria. sandoglobulin will be employed as a comparative control.


Eligibility criteria:
inclusion criteria concurrent medication: allowed: * zidovudine (azt). * acyclovir. * experimental maintenance or prophylactic therapy with an approved therapeutic agent for a non-viral opportunistic infection. * trimethoprim / sulfamethoxazole (tmp / smx). * pyrimethamine / sulfadoxine. * inhaled pentamidine. * amphotericin b. * ketoconazole. * flucytosine (5-fc). * antituberculosis therapy. * recombinant human erythropoietin. * recombinant granulocyte-macrophage colony-stimulating factor (gm-csf). * recombinant human interferon alfa 2 for aids-related kaposi's sarcoma. patients must have: * aids or be hiv positive with cd4 lymphocyte counts below 200 cells/mm3 and be receiving prophylaxis for pneumocystis carinii pneumonia (pcp) (with or without prophylaxis for another opportunistic infection), but have no prior medical history of an opportunistic infection. * expected survival of = or \> 6 months. * willingness and ability to give written informed consent. * a copy of the signed and witnessed consent form must be maintained with the investigator's study files. * positive culture results documenting the presence of cytomegalovirus (cmv) viremia and/or viruria. * seropositive for the presence of circulating anti-cmv immunoglobulin. exclusion criteria co-existing condition: patients with the following conditions or symptoms are excluded: * significant pulmonary dysfunction. * uncontrolled or unstable diabetes. * significant cardiovascular disease including uncontrolled hypertension, congestive heart failure, cardiac arrhythmia, angina pectoris, or a history of myocardial infarction within one year of entry into the study. * coagulation or hemorrhagic disorders. * any active severe opportunistic infection. concurrent medication: excluded: * therapy with ganciclovir (dhpg) or phosphonoformate (pfa) or other experimental anti-cytomegalovirus therapy except as stipulated in this protocol. * any other experimental antiviral therapy. * biologicals including immunoglobulin therapy (except those patients randomized to receive sandoglobulin as specified in this protocol). patients with the following are excluded: * any significant organ system dysfunction as described in exclusion co-existing conditions. * previous history of or evidence of idiopathic thrombocytopenia purpura, agammaglobulinemia, or hypogammaglobulinemia. * any other severe concomitant clinical condition. * documented, active cytomegalovirus (cmv) disease (tissue or organ invasion/dysfunction) at baseline. to this end, baseline indirect funduscopy (to detect and exclude patients with peripheral cmv retinitis) will be performed. prior medication: excluded within 2 weeks of study entry: * therapy with ganciclovir (dhpg) or phosphonoformate (pfa) or other experimental anti-cytomegalovirus therapy except as stipulated in this protocol. * any other experimental antiviral therapy. * biologicals including immunoglobulin therapy (except those patients randomized to receive sandoglobulin as specified in this protocol). * excluded: * prior treatment with monoclonal antibodies derived from any animal species. prior treatment: excluded within 2 weeks of study entry: * major surgery.

Keywords: aids-related opportunistic infections immunotherapy drug evaluation cytomegalovirus infections antibodies, monoclonal