Detoxified J5 Core Glycolipid/ Group B Meningococcal Outer Membrane Protein Vaccine for Gram-negative Bacterial Sepsis Administered With and Without Synthetic CPG Oligodeoxynucleotide 7909 Adjuvant

Bacterial Sepsis Clinical Trial

Official title: A Randomized, Partial-Blinded, Placebo-Controlled, Phase I Safety and Immunogenicity Study in Healthy Subjects of Detoxified J5 Core Glycolipid/ Group B Meningococcal Outer Membrane Protein Vaccine for Gram Negative Bacterial Sepsis Administered With and Without Synthetic CPG Oligodeoxynucleotide 7909 Adjuvant

Status Terminated

Clinical Trial Summary

The purpose of this study is to test the safety of an experimental vaccine against sepsis (infection of the blood) alone and with an experimental adjuvant (a substance that may improve vaccine effectiveness). This study will also find out how well antibodies are made after receiving vaccine alone or vaccine combined with adjuvant. Participants will include up to 34 healthy volunteers between the ages 18-50 years. Participants will be randomly assigned to 1 of 4 groups to receive vaccine alone, vaccine with adjuvant (2 different dosages) or placebo (inactive substance). Participants will receive 3 vaccinations at different times during the study (Day 0, Day 29 and Day 59). Study procedures will include blood samples, urine samples, electrocardiogram (measures heart activity) and a completion of a memory aid to document side effects. Participation will involve 16 clinic visits and 3 follow-up telephone calls over 12 months.

Clinical Trial Description

Invasive Gram negative bacterial infection resulting in sepsis continues to command substantial morbidity and mortality despite effective antibiotics and modern intensive care. It has been estimated that there are 300,000 cases per year in the United States. The emergence of multiple antibiotic resistant strains of bacteria adds to the urgency of finding novel therapies for the treatment of gram negative sepsis. Sepsis is a systemic inflammatory condition characterized by fever, hypotension, tachypnea, and tachycardia which can lead to multiple organ/system failure and ultimately death. This study is a randomized, partial blinded, placebo-controlled phase I safety and immunogenicity study in healthy subjects of detoxified J5 core glycolipid/ group B meningococcal outer membrane protein vaccine for gram-negative bacterial sepsis administered with and without synthetic unmethylated cytosine-guanosine motif (CPG) oligodeoxynucleotide 7909 adjuvant. The primary objective of this study is to establish the safety and tolerability of the combination of vaccine and CPG 7909. The secondary objective of this study is to determine if the combination of vaccine with the CPG 7909 is more immunogenic than vaccine alone. One dosage level of vaccine based on lipopolysaccharide (LPS) content will be studied in a three-dose regimen administered intramuscularly (IM). Since prior experience indicates no significant differences in immunogenicity response between the 10 and 25 microgram (mcg) doses of vaccine, researchers will test the 10 mcg dose. Researchers will also use 2 different doses of the CPG 7909 adjuvant (500 mcg and 250 mcg). There will be a control group that receives normal saline (NS) alone (placebo). The purpose of this study is to assess whether or not this vaccine is safe and well tolerated when given with an adjuvant, CPG 7909. The other goal of this study is to ascertain whether or not the combination of vaccine and adjuvant induces a more robust antibody response to the vaccine than is observed with the vaccine alone. The study population will include approximately 28-34 healthy subjects ages 18-50 years, inclusive, recruited from existing pool of Center for Vaccine Development (CVD) subjects. Subjects will be randomized to one of four study groups: (Group 1) 10 mcg vaccine alone; (Group 2) 10 mcg vaccine plus 500 mcg CPG 7909; (Group 3) 10 mcg vaccine plus 250 mcg CPG 7909; and (Group 4) placebo (normal saline). After blood is obtained for pre-vaccination antibody levels, subjects will receive 3 vaccinations at Day 0, 29 and 59. Subjects will be followed for safety (both clinical signs and symptoms and laboratory tests) and antibody response (anti-core glycolipid antibody by enzyme linked immunosorbent assay [ELISA], and opsonophagocytic response). Assessments for reactogenicity will be done for 60 minutes post vaccination and on the first and second days after each vaccination at the CVD and via 8 day memory aid, to be completed by the subject, after each vaccination. An electrocardiogram (EKG) will be performed after each vaccination. Blood sampling will be performed on Days 0, 14, 36, 66, 120, 180, and 365 to measure the immunogenicity of the vaccine with and without adjuvant and for antibody screening. A safety evaluation will be done by telephone on Day 90, Day 150 and Day 239, and a final safety antibody and immunogenicity evaluation will be done during the clinic visit at Day 365. ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Bacterial Sepsis
• Sepsis
• Toxemia

• NCT number: NCT01164514
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Terminated
• Phase: Phase 1
• Start date: November 2011
• Completion date: February 2013