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Protocol Details

VRC 323: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability and Immunogenicity of an Influenza H10 Stabilized Stem Ferritin Vaccine, VRC-FLUNPF0103-00-VP, in Healthy Adults

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

20-I-0145

Sponsoring Institute

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 18 Years
Max Age: 70 Years

Referral Letter Required

No

Population Exclusion(s)

Children

Keywords

Flu Virus;
Respiratory Illness;
Viral Infection;
Experimental Vaccine

Recruitment Keyword(s)

None

Condition(s)

Influenza

Investigational Drug(s)

VRC-FLUNPF0103-00-VP(H10ssF-6473)

Investigational Device(s)

None

Intervention(s)

Biological/Vaccine: VRC-FLUNPF0103-00-VP (H10ssF-6473)

Supporting Site

National Institute of Allergy and Infectious Diseases

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 H10 flu, a flu strain that infects humans.

Objective:

To test the safety and effectiveness of the H10 Stabilized Stem Ferritin vaccine (VRC-FLUNPF0103-00-VP or H10ssF-6473).

Eligibility:

Healthy adults ages 18-70, , but not born between 1965-1970.

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 on/with/via a diary card for 7 days after each injection. The injection site was checked for redness, swelling, itching or bruising.

Participants had 8-10 follow-up visits over 10 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 collected for evaluation of viral infection.

Some participants had apheresis. A needle was placed into a vein in both arms. Blood is was removed through a needle in the vein of one arm. A machine removed the white cells and then the rest of the blood was returned to the participant through a needle in the other arm.

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Eligibility

INCLUSION CRITERIA:

1. Healthy adults between the ages of 18-70 years (excluding adults born between January 1, 1965 and December 31,1970)

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 2015 to the present

4. Able and willing to complete the informed consent process

5. Available for clinic visits for 40 weeks after enrollment

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

7. Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) less than or equal to 40 within the 56 days before enrollment

Laboratory Criteria within 56 days before enrollment

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

9. Total lymphocyte count greater than or equal to 800 cells/microL

10. Platelets = 125,000 - 500,000 cells/microL

11. Hemoglobin within institutional normal range or accompanied by the PI or designee approval

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

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

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

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

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

17. Total bilirubin within institutional normal range, except when otherwise consistent with Gilbert s syndrome

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

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

Criteria applicable to women of childbearing potential:

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

21. 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:

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

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 H10 influenza vaccine

10. Receipt of a licensed influenza vaccine within 6 weeks prior to enrollment

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

11. Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator

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

13. Asthma that is not well controlled

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

15. Thyroid disease that is not well controlled

16. Idiopathic urticaria within the past year

17. Autoimmune disease or immunodeficiency

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

19. 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

20. Malignancy that is active or history of malignancy that is likely to recur during the period of the study

21. 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

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

23. Guillain-Barre Syndrome

24. Previous or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented by PCR test

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.

INCLUSION OF VULNERABLE SUBJECTS

Children

Children are not eligible to participate in this clinical trial because the investigational vaccine has not been previously evaluated in adults. If the product is assessed as safe and immunogenic, other protocols designed for children may be conducted in the future.

NIH Employees

NIH employees and members of their immediate families may participate in this protocol. We will follow the Guidelines for the Inclusion of Employees in NIH Research Studies and will give each employee a copy of the 'NIH Information Sheet on Employee Research Participation' and a copy of the 'Leave Policy for NIH Employees Participating in NIH Medical Research Studies.'

Neither participation nor refusal to participate will have an effect, either beneficial or adverse, on the participant s employment or work situation. The NIH information sheet regarding NIH employee research participation will be distributed to all potential subjects who are NIH employees. The employee subject s privacy and confidentiality will be preserved in accordance with NIH CC and NIAID policies. For NIH employee subjects, consent will be obtained by an individual who is independent of the employee s team. If the individual obtaining consent is a co-worker to the subject, independent monitoring of the consent process will be included through the Bioethics Consultation Service. Protocol study staff will be trained on obtaining potentially sensitive and private information from co-workers or subordinates.


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Citations:

Ledgerwood JE, Zephir K, Hu Z, Wei CJ, Chang L, Enama ME, Hendel CS, Sitar S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Graham BS; VRC 310 Study Team. Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect. J Infect Dis. 2013 Aug 1;208(3):418-22. doi: 10.1093/infdis/jit180. Epub 2013 Apr 30. PMID: 23633407; PMCID: PMC3699006.

Kanekiyo M, Wei CJ, Yassine HM, McTamney PM, Boyington JC, Whittle JR, Rao SS, Kong WP, Wang L, Nabel GJ. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013 Jul 4;499(7456):102-6. doi: 10.1038/nature12202. Epub 2013 May 22. PMID: 23698367.

Boyoglu-Barnum S, Hutchinson GB, Boyington JC, Moin SM, Gillespie RA, Tsybovsky Y, Stephens T, Vaile JR, Lederhofer J, Corbett KS, Fisher BE, Yassine HM, Andrews SF, Crank MC, McDermott AB, Mascola JR, Graham BS, Kanekiyo M. Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses. Nat Commun. 2020 Feb 7;11(1):791. doi: 10.1038/s41467-020-14579-4. PMID: 32034141; PMCID: PMC7005838.

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Contacts:

Principal Investigator

Referral Contact

For more information:

Joseph P. Casazza III, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
NIHBC 40 - VRC BG RM 3610B
40 CONVENT DR
BETHESDA MD 20892
(301) 496-6487
jcasazza@mail.nih.gov

Pamela Costner, R.N.
National Institute of Allergy and Infectious Diseases (NIAID)
National Institutes of Health
Building 10 - Magnuson CC
Room 5-2452
10 Center Drive
Bethesda, Maryland 20892
(301) 451-8715
vaccines@nih.gov

VRC Clinic
National Institute of Allergy and Infectious Diseases (NIAID)
Vaccine Research Center
National Institutes of Health (NIH)
Bethesda, MD 20892

(301) 451-8715
vaccines@nih.gov

Clinical Trials Number:

NCT04579250

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