Dose, Safety, Tolerability and Immunogenicity of an Influenza H1 Stabilized Stem Ferritin Vaccine in Healthy Adults
Condition: Influenza Infection
MeSH terms: Influenza, Human
Intervention: VRC-FLUNPF099-00-VP (H1ssF_3928)
Intervention description: The vaccine is composed of the HA stem domain from Influenza A/New Caledonia/20/1999 (H1N1) genetically fused to the ferritin protein from H. pylori. Purified H1ssF_3928 particles display eight well-formed HA trimers that antigenically resemble the native H1 stem viral spikes.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 52.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Flu; Seasonal Allergy; Respiratory Illness; Flu Virus; Viral Infection

Summary:

      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 received 1 or 2 vaccinations by injections (shots) in the upper arm muscle over
      4 months. Participants received a thermometer and recorded their temperature and symptoms
      every day a diary card for 7 days after each injection. The injection site was checked for
      redness, swelling, or bruising.

      Participants had 9-11 follow-up visits over 12-15 months. At follow-up visits, participants
      had blood drawn and were checked for health changes or problems. Participants who reported
      influenza-like illness had nose and throat swabs for evaluation of viral infection.

      Some participants had apheresis. A needle was placed into a vein in both arms. Blood was
      removed through a needle in the vein of one arm. A machine removed the white blood cells and
      then the rest of the blood was returned to the participant through a needle in the other arm.

      A separate consent was provided to participants for genetic testing on their samples.
    

Eligibility criteria:

        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. Agreed 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.

             Participant 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 planned 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 (tuberculosis) 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

             Participant 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-Barré 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 participant's ability to give informed consent.