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

August 7, 2023 updated by: US Army Medical Research Institute of Infectious Diseases

An Exploratory, Pilot Study of the Safety and Immunogenicity of Reduced Doses of the US Yellow Fever Vaccine

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

88

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Frederick, Maryland, United States, 21702
        • United States Army Medical Research Institute of Infectious Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard Dose (Group 1)
Yellow Fever vaccine standard dose, 0.5mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX
Experimental: Fractional dose (Group 2)
Yellow Fever vaccine 1/5th standard dose, 0.1mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX
Experimental: Fractional dose (Group 3)
Yellow Fever vaccine 1/10th standard dose, 0.05mL.
Biological: Yellow Fever Vaccine
Administered subcutaneously once.
Other Names:
  • YF-VAX

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Up to one year following vaccination.
Incidence of Adverse Events of fractional doses vs standard dose of YF-VAX as determined by subject diary and clinical history and physical examination. The incidence of solicited and unsolicited adverse events will be analyzed.
Up to one year following vaccination.
Neutralizing Antibody Response
Time Frame: Up to one year following vaccination.
Compare the neutralizing antibody response rate and mean of each ARM as determined by PRNT obtained at several time points. Fractional doses will be compared to the standard dose of YF-VAX. The primary data point is post vaccination day 28.
Up to one year following vaccination.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Viremia
Time Frame: First 14 days following vaccination.
Compare the incidence and level of viremia and mean viral load by RT-PCR (copies/mL) of fractional doses vs standard dose.
First 14 days following vaccination.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

US Army Medical Research Institute of Infectious Diseases

Investigators

  • Principal Investigator: Phillip R Pittman, M.D., M.P.H., US Army Medical Research Institute of Infectious Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 7, 2021

Primary Completion (Actual)

November 2, 2022

Study Completion (Actual)

November 2, 2022

Study Registration Dates

First Submitted

March 28, 2022

First Submitted That Met QC Criteria

May 9, 2022

First Posted (Actual)

May 16, 2022

Study Record Updates

Last Update Posted (Actual)

August 14, 2023

Last Update Submitted That Met QC Criteria

August 7, 2023

Last Verified

May 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FY19-26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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