Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine, VRCFLUNPF099-00-VP, in Healthy Adults
Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine, VRCFLUNPF099-00-VP, in Healthy Adults
Background:

 The flu is a common viral infection that can be deadly for certain people. Vaccines against
 flu have been developed to teach the body to prevent or fight the infection. A new vaccine
 may help the body to make an immune response to H1 flu, a flu strain that infects humans.

 Objective:

 To test the safety and effectiveness of the H1 Stabilized Stem Ferritin vaccine
 (VRC-FLUNPF099-00-VP).

 Eligibility:

 Healthy people ages 18-70 years old who got at least 1 licensed flu vaccine since January 1,
 2014.

 Design:

 Participants will have 1 or 2 vaccination visits over 4 months. Each will take about 4-6
 hours.

 They will get the vaccine by injections (shots) in the upper arm muscle.

 Women who can get pregnant will have a pregnancy test before each injection.

 After each vaccination, participants will complete a diary card for 7 days. They will record
 their temperature, skin changes, and any symptoms that they may have.

 Participants will have 9-11 follow-up visits over 12-15 months. They will be checked for any
 health changes or problems. They will give blood samples and may give nose and throat swabs.

 Participants may have apheresis. A needle will be placed into a vein in both arms. Blood will
 be removed through a needle in the vein of one arm. A machine will remove the white blood
 cells and then the rest of the blood is returned to the participant through a needle in the
 other arm.

 Participants may sign a separate consent for genetic testing on their samples.
Study Design: This is a Phase I, open-label, dose escalation study to evaluate the dose,
 safety, tolerability, and immunogenicity of VRC-FLUNPF099-00-VP in two regimens. The
 hypotheses are that the vaccine is safe and tolerable and will elicit an immune response. The
 primary objective is to evaluate the safety and tolerability of the investigational vaccine
 in healthy adults. Secondary objectives are related to immunogenicity of the investigational
 vaccine and dosing regimen.

 Study Products: The investigational vaccine, VRC-FLUNPF099-00-VP (H1ssF_3928), was developed
 by the Vaccine Research Center (VRC), National Institute of Allergy and Infectious Diseases
 (NIAID) and is composed of Helicobacter pylori non-heme ferritin assembled with influenza
 virus H1 haemagglutinin (HA) insert to form a nanoparticle displaying eight HA stabilized
 stem trimers from A/New Caledonia/20/1999 (H1N1) influenza. The vaccine is supplied in
 single-use vials at a concentration of 180 mcg/mL. H1ssF_3928 will be administered
 intramuscularly (IM) in the deltoid muscle via needle and syringe.

 Subjects: Healthy adults between the ages of 18-70 years, inclusive.

 Study Plan: The study will evaluate the safety, tolerability and immunogenicity of 1 or 2
 doses of the H1ssF_3928 vaccine in a dose-escalation design. In Group 1, five subjects will
 receive a single low dose (20 mcg) of H1ssF_3928 on Day 0. For Group 1, the protocol requires
 1 vaccination visit, about 9 follow-up visits, and a telephone contact after vaccination.

 If the low dose is assessed as safe and well tolerated, enrollment will begin for Group 2A.
 Groups 2A, 2B, 2C, and 2D are stratified by age as shown in the vaccination schema. In Group
 2A, subjects will receive a higher dose (60 mcg) of H1ssF_3928 on Day 0. If this higher dose
 is assessed as safe and well tolerated, subjects in Group 2A may receive a second vaccination
 at week 16 and enrollment can begin for Groups 2B, 2C, and 2D. For Groups 2A, 2B, 2C, and 2D,
 the protocol requires 2 vaccination visits, about 11 follow-up visits, and a telephone
 contact after each vaccination.

 For all groups, solicited reactogenicity will be evaluated using a 7-day diary card.
 Assessment of vaccine safety will include clinical observation and monitoring of
 hematological and chemical parameters at clinical visits throughout the study.

 VRC 321 Vaccination Schema

 Group: 1; Age Cohort: 18-40; Subjects: 5; Day 0: 20 mcg; Week 16

 Group: 2A; Age Cohort: 18-40; Subjects: 12; Day 0: 60 mcg; Week 16: 60 mcg

 Group: 2B; Age Cohort: 41-49; Subjects: 12; Day 0: 60 mcg; Week 16: 60 mcg

 Group: 2C; Age Cohort: 50-59; Subjects: 12; Day 0: 60 mcg; Week 16: 60 mcg

 Group: 2D; Age Cohort: 60-70; Subjects: 12; Day 0: 60 mcg; Week 16: 60 mcg

 Total: 53*

 *Enrollment up to 70 is permitted if additional subjects are needed for safety or
 immunogenicity evaluations.

 Study Duration: Group 1: Subjects will be evaluated for 52 weeks following the vaccine
 administration and through an influenza season.

 Groups 2A, 2B, 2C, 2D: Subjects will be evaluated for 52 weeks following the last vaccine
 administration and through an influenza season.
-  INCLUSION CRITERIA:

 1. Healthy adults between the ages of 18-70 years inclusive

 2. Based on history and examination, in good general health and without history of
 any of the conditions listed in the exclusion criteria

 3. Received at least one licensed influenza vaccine from 2014 to the present

 4. Able and willing to complete the informed consent process

 5. If enrolled in Group 1: Available for clinic visits for 52 weeks after enrollment
 and through an influenza season

 6. If enrolled in Group 2A, 2B, 2C, or 2D: Available for clinic visits for 68 weeks
 after enrollment and through an influenza season

 7. Willing to have blood samples collected, stored indefinitely, and used for
 research purposes

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

 9. Physical examination and laboratory results without clinically significant
 findings and a Body Mass Index (BMI) less than or equal to 40 within the 28 days
 before enrollment

 Laboratory Criteria within 28 days before enrollment

 10. White blood cells (WBC) and differential either within institutional normal range
 or accompanied by the site Principal Investigator (PI) or designee approval

 11. Total lymphocyte count greater than or equal to 800 cells/mm^3

 12. Platelets = 125,000 - 500,000/mm3

 13. Hemoglobin within institutional normal range

 14. Serum iron either within institutional normal range or accompanied by the site PI
 or designee approval

 15. Serum ferritin within institutional normal range or accompanied by the site PI or
 designee approval

 16. Alanine aminotransferase (ALT) less than or equal to 1.25 x institutional upper
 limit of normal (ULN)

 17. Aspartate aminotransferase (AST) less than or equal to 1.25 x institutional ULN

 18. Alkaline phosphatase (ALP) <1.1 x institutional ULN

 19. Total bilirubin within institutional normal range

 20. Serum creatinine less than or equal to 1.1 x institutional ULN

 21. Negative for HIV infection by an FDA-approved method of detection

 Criteria applicable to women of childbearing potential:

 22. Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or
 serum) on the day of enrollment

 23. Agrees to use an effective means of birth control from at least 21 days prior to
 enrollment through the end of the study

 EXCLUSION CRITERIA:

 1. Breast-feeding or planning to become pregnant during the study.

 Subject has received any of the following substances:

 2. More than 10 days of systemic immunosuppressive medications or cytotoxic medications
 within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment

 3. Blood products within 16 weeks prior to enrollment

 4. Live attenuated vaccines within 4 weeks prior to enrollment

 5. Inactivated vaccines within 2 weeks prior to enrollment

 6. Investigational research agents within 4 weeks prior to enrollment or planning to
 receive investigational products while on the study

 7. Current allergy treatment with allergen immunotherapy with antigen injections, unless
 on maintenance schedule

 8. Current anti-TB prophylaxis or therapy

 9. Previous investigational H1 influenza vaccine

 10. Previous investigational ferritin-based vaccine

 11. Receipt of a licensed influenza vaccine within 6 weeks before trial enrollment

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

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

 13. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema

 14. Asthma that is not well controlled

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

 16. Thyroid disease that is not well controlled

 17. Idiopathic urticaria within the past year

 18. Autoimmune disease or immunodeficiency

 19. Hypertension that is not well controlled (baseline systolic > 140 mmHg or diastolic >
 90 mmHg)

 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 history of 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(SqrRoot)(Copyright) Syndrome

 25. 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 subject s ability to give informed consent.