AzTrials
AzTrials

Yellow FeverPhase 4YEFENCT02991495

Immunogenicity and Safety of Fractional Doses of Yellow Fever Vaccines (YEFE)

A Phase 4 study testing Stamaril, Sanofi Pasteur, Yellow fever vaccine, Bio-Manguinhos and Yellow fever vaccine, Institut Pasteur in people with Yellow Fever, run by Epicentre at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

In July 2016, the demand for yellow fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through the African continent and even to Asia, was larger than the available supply. Read more about this study

Who is it for?
Ages 9 months to 60 yearsHealthy volunteers can take part
Conditions the study is for
Yellow Fever
What is being tested?
Stamaril, Sanofi Pasteur, Yellow fever vaccine, Bio-Manguinhos and Yellow fever vaccine, Institut Pasteur
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,630 participants
Where
2 sitesin 2 countries
Study dates
6 Nov 2017to 31 Dec 2021
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 months to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult

Who may be able to join

  • Adults population: 18 to 60 years of age
  • Children population: 9 to 59 months of age
  • For HIV positive population: HIV positive on serological testing
  • If HIV infection, CD4 T-cell counts ≥200 cells/mm³ for adults or CD4 percentage >25% for children
  • Providing informed consent to participate in the study

Who cannot join

  • Contraindications to yellow fever vaccination:
  • History of yellow fever vaccination
  • Previous yellow fever infection
  • Requiring yellow fever vaccination for travelling purposes
  • Pregnancy (as determined by a urine test on the proposed day of vaccination) and lactating women
  • Refusal to participate in the study
  • Planning to move out of the study area before the end of the study follow-up

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Kenya1 site
  • KEMRI

    Kilifi

Other trials in Kenya

Uganda1 site
  • Epicentre

    Mbarara

Other trials in Uganda

About this study

Official title: A Randomized, Blinded Non-inferiority Trial on the Immunogenicity and Safety of Fractional Doses of Yellow Fever Vaccines in Kenya and Uganda

In July 2016, the demand for yellow fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through the African continent and even to Asia, was larger than the available supply. In this situation, the World Health Organization (WHO) developed recommendations for the use of fractional-dose of yellow fever vaccine as a dose-sparing strategy. These recommendations were based on limited number of clinical trials and additional studies should assess the applicability of the fractional dose to all WHO-prequalified vaccines, the persistence of neutralizing antibodies and the performance of the fractional dose in young children and populations in Africa including those with HIV.

This study aims to respond to some of the research questions that would allow broadening the recommendations on the use of fractional doses of yellow fever vaccine in emergency situations. The study will be conducted in Uganda and Kenya and the main objective is to assess the non-inferiority is seroconversion 28 days after vaccination of a fractional dose compared to full dose for each WHO-prequalified manufacturer. As secondary objectives the study will assess seroprotection 10 days and 1 year after vaccination, to assess rapidity and persistence of protective antibody levels; describe the geometric mean titre and the change in neutralizing antibody on Day 28 days after vaccination with fractional and full doses; and assess the occurrence of adverse events and serious adverse events (SAE) during 28 days after administration of fractional and full doses.

The study consists of a randomized non-inferiority trial. The study aims to start in April 2017 in the two sites and aims to recruit 960 adults. Results for the main outcome will be reviewed by the study Data and Safety Monitoring Board and one vaccine will be selected for the studies in children and HIV positive adults.

Read the detailed description

Yellow fever (YF) is a mosquito-borne viral disease that is endemic in 34 countries in the African region and 14 in South America. YF virus infection can be asymptomatic or cause a wide spectrum of disease, from mild symptoms to severe, potentially lethal illness with jaundice, renal failure and haemorrhage. The vast majority of reported cases and deaths occur in sub-Saharan Africa where yellow fever is a major health problem occurring in epidemic patterns. There is no specific treatment for yellow fever infection. However, YF vaccine is shown to be very effective for outbreak control as well as for the prevention of outbreaks. YF vaccination confers protection in most vaccinated individuals and this is considered to be life-long.

In 2016, YF outbreaks occurred in Africa (Angola, Democratic Republic of Congo (DRC) and Uganda) as well as in South America (Brazil, Colombia and Peru). Factors such increased urbanization in poor areas without proper water and sanitation systems and population movements, have the potential to contribute to increasing incidence of yellow fever and large epidemics. In July 2016, the demand for yellow fever vaccines in response to the large urban outbreaks occurring concurrently and the risk of further spread through the African continent and even to Asia, was larger than the available supply. In this situation, the World Health Organization (WHO) developed recommendations for the use of fractional-dose of yellow fever vaccine as a dose-sparing strategy. This strategy consisted on delivering 1/5th of the conventional dose and was used to vaccinate over 7 million people in Kinshasa, the capital city of DRC.

The evidence to recommend the use of fractional dosing was based on a limited number of clinical studies. However this was considered sufficient to provide emergency recommendations. In order to broaden and also possibly simplify WHO recommendations of fractional dose use in case of need for emergency campaigns, additional data is needed to respond to the important data gaps. These include the applicability of the fractional dose to all WHO-prequalified vaccines, the persistence of neutralizing antibodies and the performance of the fractional dose in young children and populations in Africa including those with HIV. Following these data gaps, WHO called for research to be conducted.

This study aims to respond to some of the research questions that would allow to broaden the recommendations on the use of fractional doses of yellow fever vaccine in emergency situations. The study will be conducted in Uganda and Kenya and the main objective is to assess the non-inferiority is seroconversion 28 days after vaccination of a fractional dose compared to full dose for each manufacturer. As secondary objectives the study will assess seroprotection 10 days and 1 year after vaccination, to assess rapidity and persistence of protective antibody levels; describe the geometric mean titre and the change in neutralizing antibody on Day 28 after vaccination with fractional and full doses; and assess the occurrence of adverse events and serious adverse events (SAE) during 28 days after administration of fractional and full doses. The study aims to recruit 960 adults (480 in Mbarara, Uganda, and 480 in Kilifi, Kenya). Results for the main outcome will be reviewed by the study Data and Safety Monitoring Board (DSMB) and if results are considered satisfactory, the study will continue with the recruitment of 420 children in Uganda and 250 HIV infected adults in Kenya, to assess non-inferiority of one of the WHO prequalified vaccines.

Conditions
Yellow Fever
Being tested
Stamaril, Sanofi Pasteur, Yellow fever vaccine, Bio-Manguinhos, Yellow fever vaccine, Institut Pasteur, Yellow fever vaccine, Chumakov Institute
Keywords
Epidemic response
Medical subject headings
Yellow Fever

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stamaril, Sanofi PasteurBiological

    1. Full dose
    2. Fractional dose: one fifth (1/5)
  • Yellow fever vaccine, Bio-ManguinhosBiological

    1. Full dose
    2. Fractional dose: one fifth (1/5)
  • Yellow fever vaccine, Institut PasteurBiological

    1. Full dose
    2. Fractional dose: one fifth (1/5)
  • Yellow fever vaccine, Chumakov InstituteBiological

    1. Full dose
    2. Fractional dose: one fifth (1/5)
  • Yellow fever vaccine, Chumakov InstituteBiological

    Also called Children sub-study

    1. Full dose
    2. Fractional dose: one fifth (1/5)
  • Yellow fever vaccine, Chumakov InstituteBiological

    Also called HIV + adults

    1. Full dose
    2. Fractional dose: one fifth (1/5)
Study groups in NCT02991495
Study groupRoleWhat they receive
Stamaril, Sanofi Pasteur: Standard doseActive comparatorSubcutaneous administration of 1 dose of a standard yellow fever vaccine
Receives: Biological: Stamaril, Sanofi Pasteur
Stamaril, Sanofi Pasteur: Fractional doseExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Stamaril, Sanofi Pasteur
Yellow fever vaccine, Bio-Manguinhos: Standard doseActive comparatorSubcutaneous administration of 1 dose of a standard yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Bio-Manguinhos
Yellow fever vaccine, Bio-Manguinhos: Fractional doseExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Bio-Manguinhos
Yellow fever vaccine, Institut Pasteur: Standard doseActive comparatorSubcutaneous administration of 1 dose of a standard yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Institut Pasteur
Yellow fever vaccine, Institut Pasteur: Fractional doseExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Institut Pasteur
Yellow fever vaccine, Chumakov Institute: Standard doseActive comparatorSubcutaneous administration of 1 dose of a standard yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute
Yellow fever vaccine, Chumakov Institute: Fractional doseExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute
YF, Chumakov Institute: Standard dose in ChildrenActive comparatorSubcutaneous administration of 1 dose of the yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute
YF, Chumakov Institute: Fractional dose in ChildrenExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute
YF, Chumakov Institute: Standard dose in HIV+ adultsActive comparatorSubcutaneous administration of 1 dose of the yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute
YF, Chumakov Institute: Fractional dose in HIV+ adultsExperimentalSubcutaneous administration of 1/5th of a standard dose of yellow fever vaccine
Receives: Biological: Yellow fever vaccine, Chumakov Institute

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Seroconversion by PRNT50 (Plaque Reduction Neutralization Test 50 value)

    Plaque reduction neutralization test will be used to quantify the titer of neutralising antibody for the virus

    Measured: 28 days post-vaccination

Secondary outcomes (3)
  1. Assessment of protection by PRNT50 (Plaque Reduction Neutralization Test 50 value)

    Plaque reduction neutralization test will be used to quantify the titer of neutralising antibody for the virus

    Measured: 10 days post-vaccination

  2. Duration of immunity

    Assessment of duration of immunity at 1 year after vaccination

    Measured: 1 year post-vaccination

  3. Assessment of adverse events and serious adverse events

    Measured: 28 days post-vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2016 (estimated)
  2. Study start6 Nov 2017
  3. Primary completion21 Feb 2018
  4. Study completion31 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,630 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02991495
Sponsor's protocol ID
YEFE_2017
Acronym
YEFE
Status last verified
Jan 2022
First submitted
7 Dec 2016
Last updated
1 Feb 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Juan-Giner A, Charrier M, Langendorf C, Namulwana ML, Logoose S, Enguita-Fernandez C, Carrillo-Alvarez E, Briand V, Mwanga J, Giustranti C, Grais RF. Carbon emissions of a vaccine trial implemented in Uganda: retrospective assessment to identify actions to enhance researchers' environmental responsibilities. BMJ Open. 2026 Jul 15;16(7):e117954. doi: 10.1136/bmjopen-2026-117954.

    PubMed 42463194
  • Juan-Giner A, Namulwana ML, Kimathi D, Grantz KH, Fall G, Dia M, Bob NS, Sall AA, Nerima C, Sahani MK, Mulogo EM, Ampeire I, Hombach J, Nanjebe D, Mwanga-Amumpaire J, Cummings DAT, Bejon P, Warimwe GM, Grais RF. Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in children (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial. Lancet Infect Dis. 2023 Aug;23(8):965-973. doi: 10.1016/S1473-3099(23)00131-7. Epub 2023 Apr 28.

    PubMed 37127047
  • Kimathi D, Juan-Giner A, Orindi B, Grantz KH, Bob NS, Cheruiyot S, Hamaluba M, Kamau N, Fall G, Dia M, Mosobo M, Moki F, Kiogora K, Chirro O, Thiong'o A, Mwendwa J, Guantai A, Karanja HK, Gitonga J, Mugo D, Ramko K, Faye O, Sanders EJ, Grais RF, Bejon P, Warimwe GM. Immunogenicity and safety of fractional doses of 17D-213 yellow fever vaccine in HIV-infected people in Kenya (YEFE): a randomised, double-blind, non-inferiority substudy of a phase 4 trial. Lancet Infect Dis. 2023 Aug;23(8):974-982. doi: 10.1016/S1473-3099(23)00114-7. Epub 2023 Apr 28.

    PubMed 37127045
  • Juan-Giner A, Kimathi D, Grantz KH, Hamaluba M, Kazooba P, Njuguna P, Fall G, Dia M, Bob NS, Monath TP, Barrett AD, Hombach J, Mulogo EM, Ampeire I, Karanja HK, Nyehangane D, Mwanga-Amumpaire J, Cummings DAT, Bejon P, Warimwe GM, Grais RF. Immunogenicity and safety of fractional doses of yellow fever vaccines: a randomised, double-blind, non-inferiority trial. Lancet. 2021 Jan 9;397(10269):119-127. doi: 10.1016/S0140-6736(20)32520-4.

    PubMed 33422245
  • Kimathi D, Juan A, Bejon P, Grais RF, Warimwe GM; YEFE and NIFTY vaccine trials teams. Randomized, double-blinded, controlled non-inferiority trials evaluating the immunogenicity and safety of fractional doses of Yellow Fever vaccines in Kenya and Uganda. Wellcome Open Res. 2019 Nov 20;4:182. doi: 10.12688/wellcomeopenres.15579.1. eCollection 2019.

    PubMed 31984244

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Stamaril, Sanofi Pasteur, Yellow fever vaccine, Bio-Manguinhos and Yellow fever vaccine, Institut Pasteur in people with Yellow Fever, run by Epicentre at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Kenya, Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Seroconversion by PRNT50 (Plaque Reduction Neutralization Test 50 value) (time frame: 28 days post-vaccination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02991495, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2022.

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