A Phase I Study of the Safety and Pharmacokinetics of Recombinant CD4 Immunoglobulin G (rCD4-IgG) in Infants and Children With Documented HIV-1 Infection

A Phase I Study of the Safety and Pharmacokinetics of Recombinant CD4 Immunoglobulin G (rCD4-IgG) in Infants and Children With Documented HIV-1 Infection

To determine the safety profile, assess pharmacokinetic properties (blood levels), and obtain preliminary indication of the antiviral and immunologic effects of recombinant CD4 immunoglobulin G (CD4-IgG).

CD4-IgG may be effective in blocking HIV transmission and spread, that is, CD4-IgG has antiviral effects. Studies done in adult patients with AIDS and AIDS related complex (ARC) have shown that rCD4 can be safely administered by intravenous bolus, intramuscular or subcutaneous injection. No serious or dose-limiting, drug-related toxicities have been observed to date.

CD4-IgG may be effective in blocking HIV transmission and spread, that is, CD4-IgG has antiviral effects. Studies done in adult patients with AIDS and AIDS related complex (ARC) have shown that rCD4 can be safely administered by intravenous bolus, intramuscular or subcutaneous injection. No serious or dose-limiting, drug-related toxicities have been observed to date.

Patients receive one intravenous injection the first week, followed by a 6 day washout period and then intravenous injections on a twice weekly basis from week 2 to week 12. The dose per injection may vary. The study evaluates 2 groups: (1) Children 3 months to 5 years of age; (2) Infants 0-3 months of age.

Inclusion Criteria

Patients must have the following:

• HIV-1 infection, or if less than 15 months old, born to mother with HIV-1 infection.
• Legally qualified guardian with the ability to sign a written, informed consent form.
• Willingness to abstain from all other experimental therapy for HIV-1 infection during the first 12 weeks of the study period.
• Anticipated life expectancy of at least 3 months.

Prior Medication:

Allowed:

• Prophylactic anti-Pneumocystis carinii pneumonia (PCP) or antifungal therapy.
• Gamma globulin as prophylaxis for measles and varicella.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

• Past or present history of neurological abnormalities including withdrawal syndrome or seizures.
• Past or present history of any serious active opportunistic infection including Pneumocystis carinii pneumonia (PCP).
• Echocardiogram values > 2 standard deviations from normal.
• Hematologic, renal, or hepatic insufficiency.

Concurrent Medication:

Excluded:

• Zidovudine (AZT).
• Intravenous gamma globulin (IVIG) except as prophylaxis for measles and varicella.
• Cancer chemotherapy.
• Corticosteroids.
• Other known immunomodulatory agents.
• Other experimental therapy not specifically allowed.

Patients with the following are excluded:

• Hematologic, renal, or hepatic insufficiency.
• Past or present history of any serious active opportunistic infection.

Prior Medication:

Excluded for a minimum of 3 weeks prior to study entry:

• Zidovudine (AZT).
• Intravenous gamma globulin (IVIG).
• Cancer chemotherapy.
• Immunomodulatory agents.
• Acyclovir and other experimental therapy.

Risk Behavior:

Excluded:

• Patients born to substance abusing mothers (including alcohol) during the pregnancy.