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

• Status: Completed
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sandoz
• Treatments: Antibodies; Antibodies, Monoclonal; Antiviral Agents; Immunoglobulins

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.