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 Inactiva

• Status: Completed
• Trial end date: 2010-06-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Vaccines

Criteria

• INCLUSION CRITERIA:

A subject must meet all of the following criteria:

1. 18 to 70 years old.

2. Available for clinical follow-up through Week 24.

3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.

4. Complete an AoU prior to enrollment and verbalize understanding of all questions answered incorrectly.

5. Able and willing to complete the informed consent process.

6. Willing to donate blood for sample storage to be used for future research.

7. No evidence of previously undiagnosed clinically significant chronic diseases.

8. 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:

9. Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.5 g/dL for men

10. White blood cells (WBC) = 3,300-12,000 cells/mm(3)

11. Differential either within institutional normal range or accompanied by site physician approval as a differential that is consistent with healthy volunteer status

12. Total lymphocyte count greater than or equal to 800 cells/ mm(3)

13. Platelets = 125,000 - 500,000/ mm(3)

14. Alanine aminotransferase (ALT) less than or equal to 2.5 times the upper limit of normal (ULN)

15. Serum creatinine less than or equal to 1 x ULN (less than or equal to 1.3 mg/dL for females; less than or equal to 1.4 mg/dL for males) and estimated glomerular filtration rate greater than 60.

16. Negative FDA-approved HIV blood test. [Note: Results of HIV enzyme-linked immunosorbent assay (ELISA) will be documented, but a negative HIV polymerase chain reaction (PCR) test result will be sufficient for eligibility screening of subjects with positive HIV ELISA that is due to prior participation in an HIV vaccine study].

Female-Specific Criteria:

17. Negative human chorion gonadotropin (beta-HCG) pregnancy test (urine or serum) for women presumed to be of reproductive potential.

18. A female subject must meet one of the following criteria:

No reproductive potential because of menopause [one year without menses] or because of a hysterectomy, bilateral oophorectomy, or tubal ligation,

OR

Agrees to be heterosexually inactive at least 21 days prior to enrollment and through Week 24 of the study,

OR

Agrees to consistently practice contraception at least 21 days prior to enrollment and through Week 24 of the study by one of the following methods:

• condoms, male or female, with or without a spermicide;

• diaphragm or cervical cap with spermicide;

• intrauterine device;

• contraceptive pills, patch, implant or any other FDA-approved contraceptive method;

• male partner has previously undergone a vasectomy.

EXCLUSION CRITERIA:

A subject will be excluded if one or more of the following conditions apply.

Women Specific:

1. 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:

2. 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.]

3. Immunized with a current season FDA-approved influenza vaccine prior to enrollment.

4. 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).

5. Blood products within 112 days (16 weeks) prior to HIV screening

6. Immunoglobulin within 56 days (8 weeks) prior to HIV screening

7. Live attenuated vaccines within 28 days (4 weeks) prior to initial study vaccine administration

8. Investigational research agents within 28 days (4 weeks) prior to initial study vaccine administration

9. 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

10. Current anti-TB prophylaxis or therapy

Subject has a history of any of the following clinically significant conditions:

11. Autoimmune disease or immunodeficiency.

12. Contraindication to receiving an FDA approved current seasonal influenza vaccination (e.g., egg allergy).

13. Serious reactions to vaccines that preclude receipt of study vaccinations as determined by the investigator.

14. Hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.

15. Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or intravenous corticosteroids.

16. Diabetes mellitus (type I or II), with the exception of gestational diabetes.

17. Thyroid disease that is not well controlled.

18. Idiopathic urticaria within the past 1 year.

19. Hypertension that is not well controlled by medication or is more than 145/95 at enrollment.

20. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.

21. Malignancy that is active or treated malignancy for which there is not reasonable assurance of sustained cure or malignancy that is likely to recur during the period of the study.

22. Seizure disorder other than: 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years.

23. Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen.

24. Guillain-Barr Syndrome.

25. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5 years prior to enrollment, a history of suicide plan or attempt.

Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent.