VRC 307: A Double-Blind, Randomized Phase I Study of the Safety and Immunogenicity of a Prime-Boost Schedule of the Investigational DNA Trivalent Influenza Vaccine, VRC-FLUDNA047-00-VP, Followed by the 2008/2009 Seasonal Influenza Trivalent Inactivat...

NCT00858611 | Completed Phase 1

• 2 other identifiers: 09009009-I-0090
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives:

• To evaluate the safety and tolerability of a prime-boost study regimen that includes the recombinant DNA vaccine followed by licensed 2008/2009 FluLaval(Registered Trademark) in adults ages 18-50 years and adults ages 51-70 years as compared with control groups that receive the licensed vaccine only.
• To evaluate whether the study participants in each age group receiving a prime-boost schedule have a greater frequency of H1 or H3 neutralizing antibodies compared with those of the same age group who received only the 2008/2009 trivalent influenza vaccine.
• To evaluate differences in antibody or T cell responses (quantity, quality, or durability) between the two groups. Eligibility:
• Participants ages 18 to 70 years of age who are available for clinic follow-up through Week 24 and who have no previously undiagnosed clinically significant chronic diseases. Participants will provide blood samples for further testing to determine eligibility. Females must not be or become pregnant during the study.
• Volunteers who have been immunized with the current season FDA-approved influenza vaccine (2008-2009), or who are being treated for tuberculosis may not participate. Design:
• The study lasts for 24 weeks.
• Week 0: The first day of Week 0 (i.e., Day 0) is defined as the day of enrollment and first injection. Specific eligibility is reviewed. Participants will receive an injection of either the DNA vaccine VRC-FLUDNA047-00-VP (at 4 mg dosage) or a placebo.
• Week 4: All study participants will receive an injection of the trivalent seasonal influenza vaccine, according to the manufacturer's package insert directions.
• Participants will be given 7-day diary cards on which to record temperature and symptoms (e.g., muscle aches, headache, chills, nausea) and injection site reactions (e.g., pain, tenderness). Participants may also enter this information via the Internet. Presence of symptoms may require additional visits to the clinic.
• Participants will return to the clinic 2 weeks after each injection for the following procedures:
• Blood draws for further tests to determine the immune system's response to the vaccine(s) Clinical evaluations: vital signs and weight, examinations of the lymph nodes, and targeted physical exam on any visit if indicated by interim complaints or laboratory findings.

Conditions

Influenza, Human

Keywords

Influenza; Healthy; Immunity; Preventive; Flu; Healthy Volunteer; HV

Outcome Measures

Primary Outcomes (1)

• safety (local and systemic reactogenicity, lab tests, AEs)

Secondary Outcomes (1)

• lmmunogenlcity (cellular and humoral immune function assays)

Interventions

VRC-FLUDNA047-00-VP DRUG

Flulaval (Registered) Seasonal Influenza Vaccine DRUG

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A subject must meet all of the following criteria:
• to 70 years old.
• Available for clinical follow-up through Week 24.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Complete an AoU prior to enrollment and verbalize understanding of all questions answered incorrectly.
• Able and willing to complete the informed consent process.
• Willing to donate blood for sample storage to be used for future research.
• No evidence of previously undiagnosed clinically significant chronic diseases.
• Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) greater than or equal to 18.5 and less than 40 within the 28 days prior to enrollment.
• Laboratory Criteria within 56 days prior to enrollment:
• Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men
• White blood cells (WBC) = 3,300-12,000 cells/mm(3)
• Differential either within institutional normal range or accompanied by site physician approval as a differential that is consistent with healthy volunteer status
• Total lymphocyte count greater than or equal to 800 cells/ mm(3)
• Platelets = 125,000 - 500,000/ mm(3)

You may not qualify if:

• A subject will be excluded if one or more of the following conditions apply.
• Women Specific:
• Breast-feeding or planning to become pregnant during the first 28 weeks after enrollment in the study.
• Subject has received any of the following substances:
• Systemic immunosuppressive medications or cytotoxic medications, within the 12 weeks prior to enrollment. \[With the exceptions that a short-acting beta-agonists in controlled asthmatics; or a short course (duration of 10 days or less or a single injection) of corticosteroids for a self-limited condition at least 2 weeks prior to enrollment in this study will not exclude study participation.\]
• Immunized with a current season FDA-approved influenza vaccine prior to enrollment.
• Influenza infection within 6 months prior to enrollment (as assessed by clinician review of subject's self-report of a clinical course consistent with influenza).
• Blood products within 112 days (16 weeks) prior to HIV screening
• Immunoglobulin within 56 days (8 weeks) prior to HIV screening
• Live attenuated vaccines within 28 days (4 weeks) prior to initial study vaccine administration
• Investigational research agents within 28 days (4 weeks) prior to initial study vaccine administration
• Medically indicated subunit or killed vaccines (e.g., pneumococcal, or allergy treatment with antigen injections) within 14 days (2 weeks) of initial study vaccine administration
• Current anti-TB prophylaxis or therapy
• Subject has a history of any of the following clinically significant conditions:
• Autoimmune disease or immunodeficiency.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Subbarao K, Murphy BR, Fauci AS. Development of effective vaccines against pandemic influenza. Immunity. 2006 Jan;24(1):5-9. doi: 10.1016/j.immuni.2005.12.005.

  PMID: 16413916 BACKGROUND

• Luke CJ, Subbarao K. Vaccines for pandemic influenza. Emerg Infect Dis. 2006 Jan;12(1):66-72. doi: 10.3201/eid1201.051147.

  PMID: 16494720 BACKGROUND

• Beigel JH. Influenza. Crit Care Med. 2008 Sep;36(9):2660-6. doi: 10.1097/CCM.0b013e318180b039.

  PMID: 18679129 BACKGROUND

• Ledgerwood JE, Hu Z, Costner P, Yamshchikov G, Enama ME, Plummer S, Hendel CS, Holman L, Larkin B, Gordon I, Bailer RT, Poretz DM, Sarwar U, Kabadi A, Koup R, Mascola JR, Graham BS; VRC 307 and VRC 309 Study Teams. Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost. Contemp Clin Trials. 2015 Sep;44:112-118. doi: 10.1016/j.cct.2015.08.006. Epub 2015 Aug 12.

  PMID: 26275339 DERIVED

• Enama ME, Hu Z, Gordon I, Costner P, Ledgerwood JE, Grady C; VRC 306 and 307 Consent Study Teams. Randomization to standard and concise informed consent forms: development of evidence-based consent practices. Contemp Clin Trials. 2012 Sep;33(5):895-902. doi: 10.1016/j.cct.2012.04.005. Epub 2012 Apr 20.

  PMID: 22542645 DERIVED

MeSH Terms

Conditions

Influenza, Human

Interventions

FluLaval

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 7, 2009
• First Posted: March 10, 2009
• Study Start: March 3, 2009
• Primary Completion: June 21, 2010
• Study Completion: June 21, 2010
• Last Updated: July 2, 2017

Record last verified: 2010-06-21

Locations

US (1)