Safety and Efficacy Study of Fluzone® Vaccine Combined With Different Doses of JVRS-100 Adjuvant (H-100-001)

Randomized, Double Blind, Controlled Phase I Trial of the Safety, Tolerability and Immunogenicity of Fluzone® Inactivated Trivalent Influenza Virus Vaccine Administered With Ascending Doses of JVRS-100 Adjuvant

This study is designed to assess safety, tolerability and immunogenicity of Fluzone® vaccine with four dose levels of JVRS-100 adjuvant compared to Fluzone® vaccine alone in healthy adults 18-49 years of age.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Fluzone vaccine with JVRS-100 adjuvant; Biological: Fluzone vaccine; Biological: Fluzone vaccine

Detailed Description

The purpose of this trial is to evaluate the safety and tolerability of graded, ascending doses of JVRS-100 adjuvant when administered in combination with a vaccine antigen.

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Miami Research Associates
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• able to understand the study and provide written informed consent
• be age 18 to 49 years
• be in good general health, without significant medical history, physical examination findings, or abnormal laboratory results
• be available for the study duration, including all planned follow-up visits
• female subjects of child bearing potential must not be pregnant and agree to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before the study and during the study

Exclusion Criteria:

• have allergy to eggs or other components of the vaccine
• have had an influenza vaccine within 3 years preceding the screening visit
• have a history of severe reaction of any kind to conventional influenza vaccines
• have or suspected immunodeficiency disorder, including leukemia, lymphoma, generalized malignancy, or treatment with immunosuppressive medications, including corticosteroids, alkylating agents, antimetabolites, or radiation therapy
• have a history of an autoimmune disorder, including systemic lupus, rheumatoid arthritis, scleroderma, other collagen vascular disease, multiple sclerosis, etc. Psoriasis limited to cutaneous manifestations is not an exclusion criterion.
• have prior history of anaphylaxis to foods, hymenoptera stings, vaccines or drugs
• have had transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within 3 months of the Screening Visit or anticipated through the study period
• have received another vaccine within 30 days preceding the screening visit or anticipated through the study period
• have participation in another clinical trial within 60 days of the screening visit
• have a positive serum or urine pregnancy test prior to vaccination or plan on a pregnancy during study period
• have abnormalities on laboratory assessment
• be seropositive to HIV or HCV or positive for HBsAg
• be positive for anti-nuclear antibodies
• have a physical examination indicating any clinically significant medical condition
• have a body temperature >38.1°C (100.6°F) or acute illness within 3 days prior to vaccination
• intention to travel out of the area prior to the study visit on Day 28 of the study
• have a history of excessive alcohol consumption, drug abuse, significant psychiatric illness
• have the intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 28 of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Arm includes treatment with Fluzone® vaccine mixed with study product JVRS-100 adjuvant	Biological: Fluzone vaccine with JVRS-100 adjuvant; One vaccination on Day 0 with Fluzone vaccine at 22.5µg mixed with JVRS-100 adjuvant at one of four dose levels (7.5µg, 25µg, 75µg, 225µg) given by IM injection in the upper deltoid.; Other Names: Fluzone vaccine; adjuvant
Active Comparator: 2; Arm includes treatment with half adult dose of Fluzone® vaccine	Biological: Fluzone vaccine; One vaccination on Day 0 with Fluzone vaccine at 22.5µg given by IM injection in the upper deltoid.; Other Names: Flu vaccine; Biological: Fluzone vaccine; One vaccination on Day 0 with Fluzone vaccine at 45µg given by IM injection in the upper deltoid.; Other Names: Flu vaccination
Active Comparator: 3; Arm includes treatment with full adult dose Fluzone® vaccine	Biological: Fluzone vaccine; One vaccination on Day 0 with Fluzone vaccine at 22.5µg given by IM injection in the upper deltoid.; Other Names: Flu vaccine; Biological: Fluzone vaccine; One vaccination on Day 0 with Fluzone vaccine at 45µg given by IM injection in the upper deltoid.; Other Names: Flu vaccination

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison of adverse events between treatment groups	Active Study Duration
Dose-response analysis of HAI geometric mean titers (GMT)	5 time points

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety endpoints include between treatment group analyses of all safety parameters as described for the primary endpoint for each ascending dose cohort.	2 periods
Seroprotection and seroconversion rates to various antigens, distribution of antibody titers, duration of HAI antibody titers, and assessment of cross-reactive HAI responses against "drifted" strains.	5 time points

Collaborators and Investigators

• Sponsor: Colby Pharmaceutical Company
• Investigators: Study Director: Thomas P Monath, MD, Medical Monitor for Juvaris

Publications and helpful links

General Publications

• Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003 Jan 8;289(2):179-86. doi: 10.1001/jama.289.2.179.
• Betts RF, Treanor JJ. Approaches to improved influenza vaccination. Vaccine. 2000 Feb 25;18(16):1690-5. doi: 10.1016/s0264-410x(99)00508-3.
• Monto AS, Kioumehr F. The Tecumseh Study of Respiratory Illness. IX. Occurence of influenza in the community, 1966--1971. Am J Epidemiol. 1975 Dec;102(6):553-63. doi: 10.1093/oxfordjournals.aje.a112193.
• Barker WH. Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States, 1970-78. Am J Public Health. 1986 Jul;76(7):761-5. doi: 10.2105/ajph.76.7.761.
• Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25-44. doi: 10.1093/oxfordjournals.epirev.a036250. No abstract available.
• Pfleiderer M, Lower J, Kurth R. Cold-attenuated live influenza vaccines, a risk-benefit assessment. Vaccine. 2001 Dec 12;20(5-6):886-94. doi: 10.1016/s0264-410x(01)00386-3.
• Hilleman MR. Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control. Vaccine. 2002 Aug 19;20(25-26):3068-87. doi: 10.1016/s0264-410x(02)00254-2.
• CBER. Guidance for Industry. Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines. May 2007. Available at hhtp://www.fda.gov/cber/guidelines.htm
• Advisory Committee on Immunization Practices; Smith NM, Bresee JS, Shay DK, Uyeki TM, Cox NJ, Strikas RA. Prevention and Control of Influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006 Jul 28;55(RR-10):1-42. Erratum In: MMWR Morb Mortal Wkly Rep. 2006 Jul 28;55(29):800.
• de Jong JC, Palache AM, Beyer WE, Rimmelzwaan GF, Boon AC, Osterhaus AD. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol (Basel). 2003;115:63-73.
• Beyer WE, Palache AM, Luchters G, Nauta J, Osterhaus AD. Seroprotection rate, mean fold increase, seroconversion rate: which parameter adequately expresses seroresponse to influenza vaccination? Virus Res. 2004 Jul;103(1-2):125-32. doi: 10.1016/j.virusres.2004.02.024.
• Banzhoff A, Nacci P, Podda A. A new MF59-adjuvanted influenza vaccine enhances the immune response in the elderly with chronic diseases: results from an immunogenicity meta-analysis. Gerontology. 2003 May-Jun;49(3):177-84. doi: 10.1159/000069172.
• CBER. Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. Guidance. September 2007. Available at hhtp://www.fda.gov/cber/guidelines.htm

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: April 15, 2008
• First Submitted That Met QC Criteria: April 17, 2008
• First Posted (Estimate): April 21, 2008

Study Record Updates

• Last Update Posted (Estimate): March 17, 2010
• Last Update Submitted That Met QC Criteria: March 15, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Influenza vaccine; Adjuvant; Flu; Safety of an adjuvanted vaccine; Immune response to an adjuvanted vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: H-100-001