A Phase I Trial of APL 400-003 Vaccine: Safety and Immune Response Evaluations of Multiple Injections at Escalating Doses in Asymptomatic HIV-Infected Patients

Facilitated DNA inoculation, a new type of DNA vaccine, involves direct injection of non-infectious HIV genes into a patient's muscle, along with agents that promote uptake of the genes into host cells. Host cells that have taken up these genes then produce viral proteins in a form that elicits immune responses in the form of antibodies, killer T-cells, and helper T-cells. The safety of this new vaccine approach needs to be assessed.

PER 2/27/96 AMENDMENT: The Biojector 2000 provides an option for delivering the vaccine without a needle and employs a single-use syringe to avoid cross-contamination.

Patients are given intramuscular injections of APL 400-003 at one of three doses (30, 100, or 300 mcg) on day 0 and again at weeks 10 and 20, and followed for 16 weeks after the final dose. An 8-week period prior to initial dosing is required for immortalizing the patient's PBMCs.

PER 2/27/96 AMENDMENT: Five patients will be evaluated at the 300 mcg dose with the Biojector 2000.

Inclusion criteria

Concurrent Medication:

Allowed:

• Low doses of nonprescription NSAIDS, acetaminophen, ibuprofen, aspirin, replacement hormone therapy, and vitamin supplements.

Patients must have:

• Asymptomatic HIV infection with no acute related infection.
• CD4 count >= 500 cells/mm3.
• Normal hematologic, renal, hepatic, metabolic, and endocrine function.

NOTE:

• No more than one patient over 50 years of age is permitted at each dose level.

Exclusion criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Residual toxicity from prior drug treatment.
• Hypersensitivity to bupivacaine or amide-type local anesthetic.
• Active viral hepatitis, autoimmune disorders, or other debilitating chronic diseases.

Concurrent Medication:

Excluded:

• Medications that affect immune function.
• Antiretrovirals.

Patients with the following prior conditions are excluded:

• Malignancies other than curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
• History of anaphylaxis to vaccines.

Prior Medication:

Excluded:

• Prior immunization with any experimental HIV vaccines.
• Other experimental therapy within 30 days prior to study entry.
• Prior cancer chemotherapy.
• Antiretrovirals within 3 months prior to study entry.

Prior Treatment:

Excluded:

• Prior radiotherapy. IV drug use or any other high-risk behavior.