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

NCT01164514 | Terminated Phase 1

• 2 other identifiers: 04-086N01AI80057C
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bacterial Sepsis

Keywords

bacterial sepsis, septicemia, vaccine

Outcome Measures

Primary Outcomes (1)

• Clinical measures: severity and duration of systemic and local adverse events (AEs), and vaccine-related serious adverse events (SAEs)

  Solicited local and systemic adverse events (AEs) within 8 days post vaccination (Day 0-7); vaccine-related serious adverse events (SAEs) throughout the course of the study.

Secondary Outcomes (1)

• Immunogenicity measures: mean fold-increase in anti-J5 detoxified lipopolysaccharide (dLPS) IgG and IgM levels in serum and percent of subjects having >/= 4-fold IgG and IgM antibody titer response, time to seroconversion.

  Blood sampling Days 0, 14, 36, 66, 120, 180 and 365.

Study Arms (4)

Group 1 - vaccine alone

ACTIVE COMPARATOR

8 subjects to receive vaccine (10 mcg) alone on Days 0, 29 and 59.

Biological: J5-OMP Vaccine

Group 3 - vaccine + CPG 7909 (250 mcg)

EXPERIMENTAL

8 subjects to receive vaccine (10 mcg) with 250 mcg of adjuvant on Days 0, 29 and 59.

Biological: CPG 7909; Biological: J5-OMP Vaccine

Group 2 - vaccine + CPG 7909 (500 mcg)

EXPERIMENTAL

8 subjects to receive vaccine (10 mcg) with 500 mcg of adjuvant on Days 0, 29 and 59.

Biological: CPG 7909; Biological: J5-OMP Vaccine

Group 4 - Placebo

PLACEBO COMPARATOR

4 subjects to receive normal saline (placebo) on Days 0, 29 and 59.

Drug: Placebo

Interventions

CPG 7909 BIOLOGICAL

CPG 7909 is a synthetic oligodeoxynucleotide used as an adjuvant and administered at 2 different dosages: 250 mcg and 500 mcg.

Group 2 - vaccine + CPG 7909 (500 mcg); Group 3 - vaccine + CPG 7909 (250 mcg)

J5-OMP Vaccine BIOLOGICAL

J5-OMP vaccine 10 mcg to be administered with and without CpG 7909 adjuvant 250 or 500 mcg, intramuscularly on Days 0, 29 and 59.

Group 1 - vaccine alone; Group 2 - vaccine + CPG 7909 (500 mcg); Group 3 - vaccine + CPG 7909 (250 mcg)

Placebo DRUG

Normal saline.

Group 4 - Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female ages 18-50 years, inclusive.
• The subject has provided written informed consent prior to any study procedures.
• Able to attend scheduled visits and comply with trial procedures.
• Women of child-bearing potential or their partners must be surgically sterile or must agree to use an effective method of contraception and agree to remain on that same method through Day 120. Male subjects or their partners must be surgically sterile or must agree to use effective contraception through Day 120. (e.g. hormonal contraceptives initiated at least 30 days prior to receipt of vaccine, intrauterine devices (IUDs), diaphragm in combination with contraceptive jelly, condoms in combination with contraceptive jelly, cream, or foam; or vasectomized partner).
• Have normal laboratory values for hemoglobin, white blood cells (WBC) and platelets, absolute neutrophil count (ANC), absolute lymphocyte count (ALC) obtained from the complete blood count (CBC), and serum glucose and thyroid stimulating hormone (TSH). Serum alkaline phosphatase, aspartate aminotransferase (AST), alanine transferase (ALT), blood urea nitrogen (BUN), C-reactive protein (CRP) and creatinine are not to exceed the upper limit of normal, and urinalysis must be normal on day of screening visit.
• Must have a negative pregnancy test at screening (serum) and negative pregnancy test (urine) on days of vaccination, with known results prior to vaccination.
• Subject agrees to avoid non-study related blood donation for 1 year following the last immunization.

You may not qualify if:

• History of allergy or severe reaction to any vaccine or vaccine components or unmethylated cytosine-guanosine motif (CPG) components.
• Acute illness or fever \>/= 38 degrees Celsius/100.4 degrees Fahrenheit within a week prior to each vaccination.
• Prior receipt of any Group B meningococcal outer membrane protein (OMP) vaccine.
• Previous receipt of oligodeoxynucleotide adjuvant including CPG.7909.
• Immunosuppression as a result of underlying illness or treatment.
• Use of oral steroids, parenteral steroid or high-dose inhaled (\>800 mcg/day of beclomethasone dipropionate or equivalent) within 30 days prior to each vaccination.
• Acute or chronic condition that (in the opinion of the investigator) would render vaccination unsafe or would interfere with the evaluation of responses including, but not limited to the following: cardiovascular, known chronic liver disease, significant renal disease, chronic lung diseases, unstable neurologic disorder.
• Receipt of immunoglobulin or other blood product within 3 months prior to enrollment.
• Current excessive use of alcohol or drug dependence (\>8 ounces of liquor or \>96 ounces of beer/day) or a history of alcohol or drug abuse in the 5 years prior to enrollment.
• History of meningococcal infection.
• Diagnosed autoimmune condition in either subject or immediate family member.
• Under the care of a physician for a diagnosed psychiatric condition.
• Women who are pregnant or breast feeding.
• Women with a current or recent (i.e. within two half-lives) history of diuretic or promethazine use.
• The subject is immunosuppressed as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Maryland Medical System - General Clinical Research Center (GCRC)

Baltimore, Maryland, 21201-1544, United States

Location

Related Publications (1)

• Cross AS, Greenberg N, Billington M, Zhang L, DeFilippi C, May RC, Bajwa KK. Phase 1 testing of detoxified LPS/group B meningococcal outer membrane protein vaccine with and without synthetic CPG 7909 adjuvant for the prevention and treatment of sepsis. Vaccine. 2015 Nov 27;33(48):6719-26. doi: 10.1016/j.vaccine.2015.10.072. Epub 2015 Oct 26.

  PMID: 26514420 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

ProMune

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2010
• First Posted: July 16, 2010
• Study Start: November 1, 2011
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: January 31, 2014

Record last verified: 2012-08

Locations

US (1)