Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

NCT ID: NCT05374317

Last Updated: 2023-08-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-07

Study Completion Date

2022-11-02

Brief Summary

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This is an open-label, randomized, exploratory study to evaluate the human immune response to reduced subcutaneous (SQ) dosing of Yellow Fever vaccine compared to the standard FDA approved subcutaneous vaccination dose. The current dose of the US FDA licensed Yellow Fever vaccine is approximately 55,000 plaque-forming unit(s) (PFU) in 0.5 mL administered SQ. Using the licensed dosage as standard, investigators are evaluating reduced doses of 1/5th (0.10 mL) and 1/10th (0.05 mL) Yellow Fever vaccine (YF-VAX).

Detailed Description

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Up to 150 individuals will be screened in order to randomize 90 eligible individuals to one of three groups: Group 1- YF-VAX® standard dose 0.5 mL SQ = 30 subjects; Group 2-0.10 mL (1/5th) SQ = 30 subjects; Group 3-0.05 mL (1/10th) SQ = 30 subjects.

Conditions

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Yellow Fever Vaccination Reaction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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Standard Dose (Group 1)

Yellow Fever vaccine standard dose, 0.5mL.

Group Type ACTIVE_COMPARATOR

Yellow Fever Vaccine

Intervention Type BIOLOGICAL

Administered subcutaneously once.

Fractional dose (Group 2)

Yellow Fever vaccine 1/5th standard dose, 0.1mL.

Group Type EXPERIMENTAL

Yellow Fever Vaccine

Intervention Type BIOLOGICAL

Administered subcutaneously once.

Fractional dose (Group 3)

Yellow Fever vaccine 1/10th standard dose, 0.05mL.

Group Type EXPERIMENTAL

Yellow Fever Vaccine

Intervention Type BIOLOGICAL

Administered subcutaneously once.

Interventions

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Yellow Fever Vaccine

Administered subcutaneously once.

Intervention Type BIOLOGICAL

Other Intervention Names

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YF-VAX

Eligibility Criteria

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Inclusion Criteria

1. Males and Females 18 to 50 years of age.
2. In good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations.
3. Female of child bearing potential: Has a negative pregnancy test and is willing to use a reliable form of contraception for the duration of the study after vaccination.
4. Negative human immunodeficiency virus (HIV) antibody screen, seronegative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (following HIV and hepatitis testing, subjects will be provided with counseling and referral for health care if any test is positive).
5. Ability to comprehend and a willingness to sign an informed consent, which includes the Health Insurance Portability and Accountability Act (HIPAA) Authorization, and a separate consent form for HIV testing.
6. Be willing to comply with all follow-up visits, testing, adverse event (AE) reporting, and completion of diary card.

Exclusion Criteria

1. Receipt of any other investigational vaccine or investigational drug within 28 days prior to or after vaccination with YF-VAX® vaccine.
2. Have had any known flavivirus disease or receipt of any flavivirus vaccine, licensed or investigational at any time; in addition to any yellow fever vaccine, these include; Japanese Encephalitis (JE), St. Louis Encephalitis, Tick Borne Encephalitis (TBE), West Nile, Dengue, Zika virus
3. Anticipates receipt of any other vaccine within 28 days of YF-VAX®. Influenza vaccination will be permitted but not within 14 days of YF-VAX®.
4. Acute or chronic medical conditions, or medications that, in the Principal Investigator's (PI) opinion, would impair the subject's ability to respond to vaccination.
5. Hypersensitivity to any vaccine, eggs or egg products, or allergy to any component of the YF-VAX® (sorbitol, gelatin) or latex.
6. Corticosteroids even ≥20 mg/day of prednisone for ≥ 2 weeks suppresses the immune system. Low-dose corticosteroid topical products and nasal sprays used sporadically (i.e. prn--according to circumstances) are permissible.
7. History of immunosuppression, by any cause--primary or acquired immunodeficiencies, transplantation, malignant neoplasm, lymphoma, leukemia, thymoma, myasthenia gravis, radiation, immunosuppressive drugs, including antimetabolites, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), interleukin-1 (IL-1) blocking agents and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab, etc), etc.
8. Receipt of or anticipates receipt of/or donation of blood or blood products for 2 months after receipt of YF-VAX®. (Note: Blood banks require a minimum 2 week interval between the receipt of this FDA licensed vaccine and blood donations; however because of the blood collections in this study, an interval of 2 months is requested).
9. Female: Pregnant (or planning to become pregnant) or breastfeeding for the duration of the study after receipt of YF-VAX®.
10. Clinically significant abnormal laboratory tests (generally 2 times the upper limit of normal or as determined by the PI).
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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US Army Medical Research Institute of Infectious Diseases

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Phillip R Pittman, M.D., M.P.H.

Role: PRINCIPAL_INVESTIGATOR

US Army Medical Research Institute of Infectious Diseases

Locations

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United States Army Medical Research Institute of Infectious Diseases

Frederick, Maryland, United States

Site Status

Countries

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United States

References

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Monath TP, Woodall JP, Gubler DJ, Yuill TM, Mackenzie JS, Martins RM, Reiter P, Heymann DL. Yellow fever vaccine supply: a possible solution. Lancet. 2016 Apr 16;387(10028):1599-600. doi: 10.1016/S0140-6736(16)30195-7. Epub 2016 Apr 14. No abstract available.

Reference Type BACKGROUND
PMID: 27116054 (View on PubMed)

Calisher CH, Woodall JP. Yellow Fever-More a Policy and Planning Problem than a Biological One. Emerg Infect Dis. 2016 Oct;22(10):1859-60. doi: 10.3201/eid2210.160875. Epub 2016 Oct 15. No abstract available.

Reference Type BACKGROUND
PMID: 27479749 (View on PubMed)

Elachola H, Ditekemena J, Zhuo J, Gozzer E, Marchesini P, Rahman M, Sow S, Kattan RF, Memish ZA. Yellow fever outbreaks, vaccine shortages and the Hajj and Olympics: call for global vigilance. Lancet. 2016 Sep 17;388(10050):1155. doi: 10.1016/S0140-6736(16)31546-X. Epub 2016 Sep 5. No abstract available.

Reference Type BACKGROUND
PMID: 27609407 (View on PubMed)

Roukens AH, Vossen AC, Bredenbeek PJ, van Dissel JT, Visser LG. Intradermally administered yellow fever vaccine at reduced dose induces a protective immune response: a randomized controlled non-inferiority trial. PLoS One. 2008 Apr 23;3(4):e1993. doi: 10.1371/journal.pone.0001993.

Reference Type BACKGROUND
PMID: 18431480 (View on PubMed)

Slifka MK, Leung DY, Hammarlund E, Raue HP, Simpson EL, Tofte S, Baig-Lewis S, David G, Lynn H, Woolson R, Hata T, Milgrom H, Hanifin J. Transcutaneous yellow fever vaccination of subjects with or without atopic dermatitis. J Allergy Clin Immunol. 2014 Feb;133(2):439-47. doi: 10.1016/j.jaci.2013.10.037. Epub 2013 Dec 10.

Reference Type BACKGROUND
PMID: 24331381 (View on PubMed)

Campi-Azevedo AC, de Almeida Estevam P, Coelho-Dos-Reis JG, Peruhype-Magalhaes V, Villela-Rezende G, Quaresma PF, Maia Mde L, Farias RH, Camacho LA, Freire Mda S, Galler R, Yamamura AM, Almeida LF, Lima SM, Nogueira RM, Silva Sa GR, Hokama DA, de Carvalho R, Freire RA, Filho EP, Leal Mda L, Homma A, Teixeira-Carvalho A, Martins RM, Martins-Filho OA. Subdoses of 17DD yellow fever vaccine elicit equivalent virological/immunological kinetics timeline. BMC Infect Dis. 2014 Jul 15;14:391. doi: 10.1186/1471-2334-14-391.

Reference Type BACKGROUND
PMID: 25022840 (View on PubMed)

Wu JT, Peak CM, Leung GM, Lipsitch M. Fractional dosing of yellow fever vaccine to extend supply: a modelling study. Lancet. 2016 Dec 10;388(10062):2904-2911. doi: 10.1016/S0140-6736(16)31838-4. Epub 2016 Nov 10.

Reference Type BACKGROUND
PMID: 27837923 (View on PubMed)

Visser LG, Roukens AH. Modelling a way out of yellow fever. Lancet. 2016 Dec 10;388(10062):2847-2848. doi: 10.1016/S0140-6736(16)31330-7. Epub 2016 Nov 10. No abstract available.

Reference Type BACKGROUND
PMID: 27837922 (View on PubMed)

Casey RM, Harris JB, Ahuka-Mundeke S, Dixon MG, Kizito GM, Nsele PM, Umutesi G, Laven J, Kosoy O, Paluku G, Gueye AS, Hyde TB, Ewetola R, Sheria GKM, Muyembe-Tamfum JJ, Staples JE. Immunogenicity of Fractional-Dose Vaccine during a Yellow Fever Outbreak - Final Report. N Engl J Med. 2019 Aug 1;381(5):444-454. doi: 10.1056/NEJMoa1710430. Epub 2018 Feb 14.

Reference Type BACKGROUND
PMID: 29443626 (View on PubMed)

Martins RM, Maia Mde L, Farias RH, Camacho LA, Freire MS, Galler R, Yamamura AM, Almeida LF, Lima SM, Nogueira RM, Sa GR, Hokama DA, de Carvalho R, Freire RA, Pereira Filho E, Leal Mda L, Homma A. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study. Hum Vaccin Immunother. 2013 Apr;9(4):879-88. doi: 10.4161/hv.22982. Epub 2013 Jan 30.

Reference Type BACKGROUND
PMID: 23364472 (View on PubMed)

Yellow fever vaccine: WHO position on the use of fractional doses - June 2017. Wkly Epidemiol Rec. 2017 Jun 23;92(25):345-50. No abstract available. English, French.

Reference Type BACKGROUND
PMID: 28643507 (View on PubMed)

Roukens AHE, Visser LG. Fractional-dose yellow fever vaccination: an expert review. J Travel Med. 2019 Sep 2;26(6):taz024. doi: 10.1093/jtm/taz024.

Reference Type BACKGROUND
PMID: 30937437 (View on PubMed)

Hepburn MJ, Kortepeter MG, Pittman PR, Boudreau EF, Mangiafico JA, Buck PA, Norris SL, Anderson EL. Neutralizing antibody response to booster vaccination with the 17d yellow fever vaccine. Vaccine. 2006 Apr 5;24(15):2843-9. doi: 10.1016/j.vaccine.2005.12.055. Epub 2006 Jan 18.

Reference Type BACKGROUND
PMID: 16494976 (View on PubMed)

Vasconcelos PF, Monath TP. Yellow Fever Remains a Potential Threat to Public Health. Vector Borne Zoonotic Dis. 2016 Aug;16(8):566-7. doi: 10.1089/vbz.2016.2031. Epub 2016 Jul 11.

Reference Type RESULT
PMID: 27400066 (View on PubMed)

Provided Documents

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Document Type: Informed Consent Form

View Document

Related Links

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http://dx.doi.org/10.15585/mmwr.mm6617e2

Addressing a Yellow Fever Vaccine Shortage

Other Identifiers

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FY19-26

Identifier Type: -

Identifier Source: org_study_id

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