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

Sandoz

Status and phase: Completed; Phase 1

Conditions: HIV Infections; Cytomegalovirus Infections

Treatments: Drug: Sevirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002268

Study No B102

071A

Details and patient eligibility

About

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.