This study is designed to evaluate the safety of the FLSC vaccine and will be a randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers (Human Immunodeficiency Virus-1 uninfected).
This is a Phase 1 randomized, placebo-controlled, modified double-blinded dose escalation study in 60 healthy adult volunteers who are Human Immunodeficiency Virus-1 (HIV-1) uninfected. Participants in the study will receive 4 injections at 0, 4, 8 and 24 weeks and will be followed for an additional 24 weeks. The total study duration will be 48 weeks. As this is a Phase 1 trial, the primary objective is to document safety of the Full Length Single Chain (FLSC) gp120-CD4 complex vaccine with a secondary objective to evaluate immune responses induced by the vaccine. This vaccine is being evaluated as it is constructed so that the gp120 and CD4 moieties form a stable intra-chain binding interaction that forms a transition state structure that presents conserved, conformational domains involved in the early HIV replication process. It is hypothesized that antibodies directed to these epitopes would be highly cross-reactive and potentially useful for HIV vaccine development.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
65
FLSC vaccine 300 ug (1.0 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
FLSC vaccine 150 ug (0.5 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
FLSC vaccine 75 ug (0.25 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
University of Maryland, Institute of Human Virology
Baltimore, Maryland, United States
Number of Participants With Local and Systemic Reactogenicity Signs and Symptoms
Signs and symptoms include pain, tenderness, maximum severity of pain and/or tenderness, erythema, induration, fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms.
Time frame: 48 weeks
Number of Participants With Related Adverse Events
Treatment emergent adverse events assessed by investigator to be either possibly, probably, or definitely related to study treatment. Medical Dictionary for Regulatory Activities (MedDRA) preferred term, severity, and assessed relationship to study products.
Time frame: 48 weeks
Number of Participants With Sustained Decrease in CD4 Count and CD4%.
CD4 count was monitored from baseline and at each study visit through study completion. Baseline CD4 and CD4% levels were calculated by taking the average of the screening and first vaccination visits. The number of individuals who had sustained (2 consecutive time points) 30% decrease in CD4 cell/ul and CD4% from baseline were counted.
Time frame: 48 weeks
Binding Antibody Response Rates to FLSC
Percent of participants with anti-FLSC antibodies as assessed by ELISA by 2 weeks after final vaccination
Time frame: 2 weeks after 4th (last) vaccination.
Binding Antibody Response Rates to BaL-gp120
Percent of participants with anti-gp120 antibodies as assessed by ELISA
Time frame: 2 weeks after 4th (last) vaccination
Competitive Antibody Rates to CD4i Epitopes
Percent of participants with antibodies competing with A32 or 17b as assessed by ELISA.
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Placebo sterile saline (0.25 - 1.0 mL) given by intramuscular injection into the arm on study Days 0, 28, 56, 168
Time frame: 2 weeks after 4th (last) vaccination