Trial Information

A Phase I Dose Escalation Study of Lipopeptide Vaccines With Activity Against Human Cytomegalovirus

OBJECTIVES:

- To establish whether 4 dose levels of the CMVpp65-A*0201 peptide vaccine are safe and
well tolerated in cytomegalovirus (CMV)-seropositive participants.

- To determine whether the CMVpp65-A*0201 peptide vaccine, when given as a single
injection followed by one booster injection at a safe and well-tolerated dose, is
capable of stimulating a memory response in CMV-seropositive participants.

- To evaluate whether CMV-seronegative participants generate a de novo immune response
against CMV after immunization with CMVpp65-A*0201 peptide vaccine given as a single
injection followed by three booster injections.

- To determine the duration of immune enhancement of CMV-specific cytotoxic T-lymphocyte
function as assessed for up to 12 months after primary or secondary immunization with
the CMVpp65-A*0201 peptide vaccine.

OUTLINE: This is a dose-escalation study of CMVpp65-A*0201 peptide vaccine in
cytomegalovirus (CMV)-seropositive participants. Once a safe dose is established,
CMV-seronegative participants are accrued and immunized at that dose. Participants are
stratified according to gender.

- CMV-seropositive participants: Participants are randomized to receive 1 of 4 escalating
doses of CMVpp65-A*0201 peptide vaccine containing either helper T-lymphocyte (HTL)
PADRE peptide or HTL tetanus toxoid peptide. Within each vaccine dose group, two
participants are randomized to receive a placebo. Participants receive the vaccine or a
placebo subcutaneously (SC) on days 0 and 28 in the absence of unacceptable toxicity.

- CMV-seronegative participants: Participants are randomized to receive 1 of 4
established doses (established in CMV-seropositive participants) of CMVpp65-A*0201
peptide vaccine containing either HTL PADRE peptide or HTL tetanus toxoid peptide.
Participants receive the vaccine on days 0, 28, and 56 in the absence of unacceptable
toxicity. Participants with a partial or low-level immune response receive one
additional booster vaccine on day 90.

Participants undergo blood sample collection at baseline and periodically during study for
immunologic laboratory studies. Participants also undergo skin biopsy at baseline.
Laboratory studies include assessment of human cytotoxic T-lymphocyte activity and response
by ^51chromium-release assay, limiting-dilution analysis, and T-cell proliferation assay;
and CD4/CD8 phenotyping by FACScan® flow cytometry.

After completion of study therapy, participants are followed for 12 months.