A Phase I/II Trial to Assess the Safety and Tolerance of Escalating Doses of a Human Anti-Cytomegalovirus Monoclonal Antibody (SDZ MSL-109) in Patients With the Acquired Immunodeficiency Syndrome and CMV Retinitis

Sandoz

Status and phase: Completed; Phase 1

Conditions: Cytomegalovirus Retinitis; HIV Infections

Treatments: Drug: Sevirumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00002016

071B

Study No B103

Details and patient eligibility

About

To determine the safety and tolerance of 3 dosage levels of human anti-cytomegalovirus (CMV) monoclonal antibody (SDZ MSL-109) when administered once every 2 weeks for a total of 8 doses during the maintenance phase of ganciclovir (DHPG) therapy to patients with AIDS and documented evidence of CMV retinitis. In addition for those patients with positive CMV cultures upon entry into this trial a preliminary attempt will be made to assess the potential in vivo antiviral effects of the concomitant administration of DHPG and SDZ MSL-109.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Zidovudine (AZT) < 600 mg/day.
• Experimental maintenance or prophylactic therapy with an approved therapeutic agent for a non-viral opportunistic infection.
• Trimethoprim / sulfamethoxazole (TMP / SMX).
• Pyrimethamine / sulfadoxine.
• Aerosolized pentamidine.
• Ketoconazole.
• Flucytosine (5-FC).
• Antituberculosis therapy.

Concurrent Treatment:

Allowed:

• Maintenance phase of ganciclovir (DHPG) therapy.

Patients must have:

• AIDS with documented ophthalmologic findings consistent with cytomegalovirus (CMV) retinitis whose retinal lesions are less than 750 microns from the fovea and who have visual symptoms of CMV retinitis.
• Completed the treatment induction phase with ganciclovir (DHPG) and be about to participate in the maintenance phase DHPG therapy.
• 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.
• 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 amphotericin B or fluconazole.
• Any other investigational drug.
• Biologicals including immunoglobulin therapy, granulocyte-macrophage-colony-stimulating-factor (GM-CSF), erythropoietin alpha, or any interleukin.

Patients with the following are excluded:

• Any significant organ system dysfunction as described in Exclusion Co-existing Conditions.
• Any other severe concomitant clinical condition.

Prior Medication:

Excluded within 2 weeks of study entry:

• Therapy with amphotericin B or fluconazole.
• Any other investigational drug.
• Biologicals including immunoglobulin therapy, granulocyte-macrophage-colony-stimulating factor (GM-CSF), erythropoietin alpha, or any interleukin.
• Excluded:
• Prior treatment with monoclonal antibodies derived from any animal species.

Prior Treatment:

Excluded within 2 weeks of study entry:

• Major surgery.