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

NCT02991495 | Completed Phase 4 DMC

• 1 other identifier: YEFE_2017
• Study Type: interventional
• Target: 1,630
• Locations: 2 countries
• Sites: 2

Brief 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. 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.

Conditions

Yellow Fever

Keywords

Epidemic response

Outcome Measures

Primary Outcomes (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

  28 days post-vaccination

Secondary Outcomes (3)

• Assessment of protection by PRNT50 (Plaque Reduction Neutralization Test 50 value)

  10 days post-vaccination

• Duration of immunity

  1 year post-vaccination

• Assessment of adverse events and serious adverse events

  28 days post-vaccination

Study Arms (12)

Stamaril, Sanofi Pasteur: Standard dose

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of a standard yellow fever vaccine

Biological: Stamaril, Sanofi Pasteur

Stamaril, Sanofi Pasteur: Fractional dose

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Stamaril, Sanofi Pasteur

Yellow fever vaccine, Bio-Manguinhos: Standard dose

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of a standard yellow fever vaccine

Biological: Yellow fever vaccine, Bio-Manguinhos

Yellow fever vaccine, Bio-Manguinhos: Fractional dose

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Yellow fever vaccine, Bio-Manguinhos

Yellow fever vaccine, Institut Pasteur: Standard dose

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of a standard yellow fever vaccine

Biological: Yellow fever vaccine, Institut Pasteur

Yellow fever vaccine, Institut Pasteur: Fractional dose

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Yellow fever vaccine, Institut Pasteur

Yellow fever vaccine, Chumakov Institute: Standard dose

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of a standard yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

Yellow fever vaccine, Chumakov Institute: Fractional dose

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

YF, Chumakov Institute: Standard dose in Children

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of the yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

YF, Chumakov Institute: Fractional dose in Children

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

YF, Chumakov Institute: Standard dose in HIV+ adults

ACTIVE COMPARATOR

Subcutaneous administration of 1 dose of the yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

YF, Chumakov Institute: Fractional dose in HIV+ adults

EXPERIMENTAL

Subcutaneous administration of 1/5th of a standard dose of yellow fever vaccine

Biological: Yellow fever vaccine, Chumakov Institute

Interventions

Stamaril, Sanofi Pasteur BIOLOGICAL

1. Full dose 2. Fractional dose: one fifth (1/5)

Stamaril, Sanofi Pasteur: Fractional dose; Stamaril, Sanofi Pasteur: Standard dose

Yellow fever vaccine, Bio-Manguinhos BIOLOGICAL

1. Full dose 2. Fractional dose: one fifth (1/5)

Yellow fever vaccine, Bio-Manguinhos: Fractional dose; Yellow fever vaccine, Bio-Manguinhos: Standard dose

Yellow fever vaccine, Institut Pasteur BIOLOGICAL

1. Full dose 2. Fractional dose: one fifth (1/5)

Yellow fever vaccine, Institut Pasteur: Fractional dose; Yellow fever vaccine, Institut Pasteur: Standard dose

Yellow fever vaccine, Chumakov Institute BIOLOGICAL

1. Full dose 2. Fractional dose: one fifth (1/5)

Yellow fever vaccine, Chumakov Institute: Fractional dose; Yellow fever vaccine, Chumakov Institute: Standard dose

Eligibility Criteria

• Age: 9 Months - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Epicentre: lead
• Kenya Medical Research Institute: collaborator

Study Sites (2)

KEMRI

Kilifi, Kenya

Location

Epicentre

Mbarara, Uganda

Location

Related Publications (4)

• 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.

  PMID: 37127047 DERIVED

• 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.

  PMID: 37127045 DERIVED

• 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.

  PMID: 33422245 DERIVED

• 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.

  PMID: 31984244 DERIVED

MeSH Terms

Conditions

Yellow Fever

Interventions

Yellow Fever Vaccine; Seroconversion

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures; Immune System Phenomena

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 13, 2016
• Study Start: November 6, 2017
• Primary Completion: February 21, 2018
• Study Completion: December 31, 2021
• Last Updated: February 1, 2022

Record last verified: 2022-01

Locations

UG (1); KE (1)