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Immunogenicity of Fractional One-fifth and One-half Doses of Yellow Fever Vaccine Compared to Full Dose in Children 9-23 Months Old

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ClinicalTrials.gov Identifier: NCT03725618
Recruitment Status : Not yet recruiting
First Posted : October 31, 2018
Last Update Posted : October 31, 2018
Sponsor:
Collaborators:
Infectious Disease Institute, Kampala, Uganda
MRC/UVRI Uganda Research Unit on Aids
Ministry of Health, Uganda
Information provided by (Responsible Party):
Centers for Disease Control and Prevention

Brief Summary:

A randomized clinical trial comparing fractional dose Yellow Fever vaccination to the full dose among children aged 9-23 months in Uganda. Children will have immune response assessed at baseline, 4 weeks, and 12 months after vaccination.

Enrolled participants will be randomized to one of three arms:

A. One-fifth fractional dose (0.1 ml) administered subcutaneously B. One-half fractional dose (0.25 ml) administered subcutaneously C. Full dose (0.5 ml) administered subcutaneously


Condition or disease Intervention/treatment Phase
Yellow Fever Biological: Yellow Fever 17DD Vaccine Phase 4

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1788 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Immunogenicity of Fractional One-fifth and One-half Doses of Yellow Fever Vaccine Compared to Full Dose in Children 9-23 Months Old
Estimated Study Start Date : November 2018
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020


Arm Intervention/treatment
Experimental: One-fifth fractional dose
One-fifth fractional dose (0.1 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
Biological: Yellow Fever 17DD Vaccine
live attenuated vaccine based on the 17DD strain

Experimental: One-half fractional dose
One-half fractional dose (0.25 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
Biological: Yellow Fever 17DD Vaccine
live attenuated vaccine based on the 17DD strain

Experimental: Full dose
Full dose (0.5 ml) of Yellow Fever 17DD Vaccine administered subcutaneously
Biological: Yellow Fever 17DD Vaccine
live attenuated vaccine based on the 17DD strain




Primary Outcome Measures :
  1. Immune response at 4 weeks in terms of seroconversion following vaccination [ Time Frame: 4 weeks post vaccination ]
    Assess whether seroconversion following one-fifth (0.1 ml) and one-half (0.25 ml) doses of YF 17DD vaccine is non-inferior to seroconversion following a full dose (0.5 ml) at 4 weeks post-vaccination in children aged 9 - 23 months. Study endpoints at 4 weeks will be the following: Seroconversion will be defined as seronegative participants (plaque reduction neutralization test with a 50% cut-off (PRNT50) < 10) at enrollment who become seropositive (PRNT50 ≥ 10) at 4 week follow-up. A boosted response will be defined as baseline-positive participants who demonstrate a four-fold or greater change in YF virus-specific titers between the baseline and 4 week specimens, e.g. a change from 1:20 to 1:80.


Secondary Outcome Measures :
  1. Immune response at 12 months in terms of seroconversion following vaccination [ Time Frame: 12 months post vaccination ]
    Assess whether the proportion of baseline seronegative children that are seropositive following one-fifth (0.1 ml) and one-half (0.25 ml) doses of YF 17DD vaccine is non-inferior to the proportion seropositive following a full dose (0.5 ml) of vaccine at 12 months post-vaccination. At 12 months, the endpoint will be a plaque reduction neutralization test with a 50% cut-off ( PRNT50) ≥ 10 as evidence of seropositivity


Other Outcome Measures:
  1. Titers at 4weeks and 12 months [ Time Frame: 4 weeks and 12 months ]
    • Compare the geometric mean antibody titers following the fractional doses to the geometric mean titer following the full dose at 4 weeks and 12 months post vaccination

  2. Frequency of adverse events following vaccination [ Time Frame: 1 hour, 3 days, 14 days, 28 days ]
    Compare frequency of adverse events for pre-defined conditions associated with yellow fever vaccine and serious adverse events associated following vaccination, as defined by Brighton Criteria and WHO guidelines, in the trial between the 3 study arms



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Ages Eligible for Study:   9 Months to 23 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 9 to 23 months at the time of enrollment
  2. Intent to stay in the health center catchment area and availability to do study visits at 2 weeks, 4 weeks, and 12 months after enrollment date
  3. Informed consent signed by parent/guardian for child's participation in the study, including blood sample collections at 4 week and 12 month visits post-vaccination
  4. Willingness of parent/guardian to be contacted by study personnel by telephone and through home visits if they cannot be reached by telephone.

Exclusion Criteria:

  1. Verbal or written report of previous vaccination against YF
  2. Verbal or documented history of YF disease
  3. Contraindication for YF vaccine including:

    1. Allergy to eggs, gelatin, or neomycin
    2. Severe immune deficiency immunological including symptomatic HIV infection and HIV- infected persons with CD4 T-cell counts ≤200 cells/ mm³, primary immunodeficiencies, having received immunosuppressive doses of oral or injectable corticosteroids (or equivalent), having received immunomodulatory or chemotherapeutic agents
    3. Thymus disorder
    4. History of malignant neoplasm or recent hematopoietic stem cell transplantation
    5. Serious illness/fever (mild illness without fever is not an exclusion criterion)
  4. Administration of immunoglobulins or other blood derivative within 6 months of enrollment in the study or during the study

    a. Exception: children with a history of Kawasaki disease who received gammaglobulin cannot be enrolled if they received it in the previous 11 months.

  5. Administration of any other attenuated viral vaccine in the month prior to enrollment, or if the administration of any other attenuated viral vaccine is expected during the month after enrollment. Note: the administration of measles vaccine on the same day as YF vaccination is not a contraindication; however, if Uganda introduces measles-rubella vaccine (MR), participants will not be able to receive MR on the same day as YF vaccine due to possible interference between rubella and YF vaccine. In this situation, children will have to delay study enrollment until 1 month after MR vaccination.
  6. Participating in another clinical drug trial of a drug, vaccine, or medical device
  7. Severely underweight defined as ≤ 3rd percentile in the height/weight tables
  8. Severe reaction to prior vaccination
  9. Any chronic or other condition that, in the opinion of the study staff, represents a health risk to the participant or interferes with the evaluation of the response to the vaccine


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03725618


Contacts
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Contact: Terri Hyde, MD 404.639.8764 tkh4@cdc.gov

Sponsors and Collaborators
Centers for Disease Control and Prevention
Infectious Disease Institute, Kampala, Uganda
MRC/UVRI Uganda Research Unit on Aids
Ministry of Health, Uganda

Publications:
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Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT03725618     History of Changes
Other Study ID Numbers: 2017-197
First Posted: October 31, 2018    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fever
Yellow Fever
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Vaccines
Immunologic Factors
Physiological Effects of Drugs