Non-interference Study of MR and Yellow Fever Vaccines Among Bangladeshi Infants Aged 9-12 Months

NCT06815835 | Not Yet Recruiting Phase 3 DMC

• 1 other identifier: PR-24098
• Study Type: interventional
• Target: 1,530
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted among 1530 healthy infants of 9 to 12 months of age residing in the Dakshinkhan and Uttarkhan area which is located in Dhaka North City Corporation (DNCC) to enroll the required number of participants. Only infants who have not previously received the MR and YF vaccines will be enrolled. The findings of this study are likely to have a significant impact on vaccine co-administration strategies for campaign and routine immunization programs. The participants will be assigned to one of the three groups by the central computer-generated randomization schedule. The numbers are defined for each arm (Table 1) based on the sample size calculation. A list of infants who did not receive MR and Yellow fever vaccine will be prepared before enrollment by trained study staff (TSS). The TSSs will visit households in the defined study area and ask if the parents/guardians of infants aged 9-12 months are willing to participate in the study. If they show a willingness to participate, the TSSs will check their vaccination cards (if available) and prepare the list of potentially eligible infants who have not received MR and Yellow fever vaccines based on their vaccination card status. The investigators will collect blood specimens (4-5 ml) at the time of screening (visit-1), to evaluate serological markers of dengue and Japanese Encephalitis infection and for baseline (pre-vaccination) immunological assessment. The investigators will vaccinate seronegative, eligible participants within 24 hours of blood collection. There will be additional three follow-up visits after enrollment and will collect around 3-4 ml blood from each participant during visit 4 (week 6), and visit 5 (week 26) for immunological assessment. Diary cards will be used to collect adverse events (AEs) following immunization (AEFI) data for vaccinated participants (up to 14 days for solicited and 6 weeks for unsolicited AEs). Medically attended adverse events (MAAEs) and data on serious adverse events (SAEs) will be reported during the study. All study updates including AEs and SAEs will be reported to the data safety and monitoring board (DSMB) and sponsor.

Conditions

Measles; Rubella; Yellow Fever

Keywords

Safety; Non-interference; Measles and Rubella; Co-administration; Immunogenicity

Outcome Measures

Primary Outcomes (1)

• Seropositivity

  Equivalence for seropositivity rate for anti-measles, anti-rubella, and anti-YF IgG antibodies at 6 weeks post-vaccination

  06 weeks

Secondary Outcomes (2)

• Immunogenicity

  06 months

• Safety reporting

  06 months

Study Arms (3)

Test (MR+YF)

EXPERIMENTAL

Based on randomization (n= 510) potential participants will be vaccinated with MR+YF on Day 0. A diary card will be provided. A blood sample (4-5 ml) will be collected for immunological assay on Day -1, Week 6 ±3 days, and Week 26 ±7 days. All details will be recorded in the eCRF.

Biological: Measles-Rubella vaccine (Live) I.P. (Freeze Dried) of M/s. Zydus Lifesciences Ltd; Biological: Yellow fever Vaccine (WHO prequalified)

Reference 1 (MR)

EXPERIMENTAL

Based on randomization (n= 510) potential participants will be vaccinated with MR on Day 0. A diary card will be provided. A blood sample (4-5 ml) will be collected for immunological assay on Day -1, Week 6 ±3 days, and Week 26 ±7 days. All details will be recorded in the eCRF.

Biological: Measles-Rubella vaccine (Live) I.P. (Freeze Dried) of M/s. Zydus Lifesciences Ltd

Reference 2 (YF)

PLACEBO COMPARATOR

Based on randomization (n= 510) potential participants will be vaccinated with YF on Day 0. A diary card will be provided. A blood sample (4-5 ml) will be collected for immunological assay on Day -1, Week 6 ±3 days, and Week 26 ±7 days. All details will be recorded in the eCRF.

Biological: Yellow fever Vaccine (WHO prequalified)

Interventions

Measles-Rubella vaccine (Live) I.P. (Freeze Dried) of M/s. Zydus Lifesciences Ltd BIOLOGICAL

Live attenuated vaccine

Reference 1 (MR); Test (MR+YF)

Yellow fever Vaccine (WHO prequalified) BIOLOGICAL

Live attenuated vaccine

Reference 2 (YF); Test (MR+YF)

Eligibility Criteria

• Age: 9 Months - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• The participant must satisfy all the following criteria to be eligible for enrolment:
• Healthy infant participants of either gender aged\* 9 to 12 months at the time of enrollment
• Participants should be in good health as determined by the medical history and physical examination based on the clinical judgment of the investigator
• No previous history of vaccination against measles, rubella, or Yellow fever
• Written informed consent from the participant's parent/guardian
• Participant's parent/guardian literate enough to fill the diary card \*Age calculated as per completed month

You may not qualify if:

• Participants positive for serological markers against Dengue and/or Japanese Encephalitis infections
• History of hypersensitivity reaction to any component of the study vaccines including egg and chicken proteins
• History of hypersensitivity reaction to neomycin
• History of laboratory-confirmed or suspected measles, rubella, or Yellow fever in the past
• Participant exposed# to measles, rubella, or Yellow fever virus within the past 30 days
• Fever of any origin or infectious disorder of 3 days or more within the past month
• Febrile illness (axillary temperature ≥37.5°C) at the time of enrollment
• History of any vaccination within the past month
• Clinically significant systemic disorders such as cardiovascular, respiratory, neurologic, gastrointestinal, hepatic, renal, endocrine, haematological, immunological, or metabolic disorder
• Confirmed or suspected immunosuppressive or immunodeficiency disorder; or participants on any immunosuppressive or immunostimulant therapy
• Known case of thrombocytopenia or any coagulation disorder, or participants on anticoagulation therapy
• Participants administered blood, blood-containing products, or immunoglobulins within the last 3 months or planned administration during the study
• Participant participated in another clinical study in the past 3 months
• Any other reason for which the investigator feels that the participant should not participate #Close contact (family member or neighbour) with laboratory-confirmed or clinical diagnosis of measles/rubella/Yellow fever

Sponsors & Collaborators

• International Centre for Diarrhoeal Disease Research, Bangladesh: lead
• Zydus Lifesciences Limited: collaborator

Study Sites (1)

Icddr,B

Dhaka, Bangladesh

Location

Related Publications (14)

• Cracknell Daniels B, Gaythorpe K, Imai N, Dorigatti I. Yellow fever in Asia-a risk analysis. J Travel Med. 2021 Apr 14;28(3):taab015. doi: 10.1093/jtm/taab015.

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• Sacchetto L, Drumond BP, Han BA, Nogueira ML, Vasilakis N. Re-emergence of yellow fever in the neotropics - quo vadis? Emerg Top Life Sci. 2020 Dec 11;4(4):399-410. doi: 10.1042/ETLS20200187.

  PMID: 33258924 BACKGROUND

• Roukens AH, Visser LG. Yellow fever vaccine: past, present and future. Expert Opin Biol Ther. 2008 Nov;8(11):1787-95. doi: 10.1517/14712598.8.11.1787.

  PMID: 18847312 BACKGROUND

• Monath TP, Vasconcelos PF. Yellow fever. J Clin Virol. 2015 Mar;64:160-73. doi: 10.1016/j.jcv.2014.08.030. Epub 2014 Oct 24.

  PMID: 25453327 BACKGROUND

• Gaythorpe KA, Hamlet A, Jean K, Garkauskas Ramos D, Cibrelus L, Garske T, Ferguson N. The global burden of yellow fever. Elife. 2021 Mar 16;10:e64670. doi: 10.7554/eLife.64670.

  PMID: 33722340 BACKGROUND

• Monath TP. Yellow fever vaccine. Expert Rev Vaccines. 2005 Aug;4(4):553-74. doi: 10.1586/14760584.4.4.553.

  PMID: 16117712 BACKGROUND

• Asish PR, Dasgupta S, Rachel G, Bagepally BS, Girish Kumar CP. Global prevalence of asymptomatic dengue infections - a systematic review and meta-analysis. Int J Infect Dis. 2023 Sep;134:292-298. doi: 10.1016/j.ijid.2023.07.010. Epub 2023 Jul 16.

  PMID: 37463631 BACKGROUND

• Turtle L, Solomon T. Japanese encephalitis - the prospects for new treatments. Nat Rev Neurol. 2018 Apr 26;14(5):298-313. doi: 10.1038/nrneurol.2018.30.

  PMID: 29697099 BACKGROUND

• Endale A, Medhin G, Darfiro K, Kebede N, Legesse M. Magnitude of Antibody Cross-Reactivity in Medically Important Mosquito-Borne Flaviviruses: A Systematic Review. Infect Drug Resist. 2021 Oct 19;14:4291-4299. doi: 10.2147/IDR.S336351. eCollection 2021.

  PMID: 34703255 BACKGROUND

• Shi N, Rasuli A, Thollot Y. Safety of two doses of an inactivated hepatitis a vaccine given 6 months apart in healthy toddlers, children, and adolescents aged 12 months to 15 years in China: a phase IV study. Hum Vaccin Immunother. 2019;15(3):748-754. doi: 10.1080/21645515.2018.1539600. Epub 2018 Dec 5.

  PMID: 30403910 BACKGROUND

• Nolan T, McVernon J, Skeljo M, Richmond P, Wadia U, Lambert S, Nissen M, Marshall H, Booy R, Heron L, Hartel G, Lai M, Basser R, Gittleson C, Greenberg M. Immunogenicity of a monovalent 2009 influenza A(H1N1) vaccine in infants and children: a randomized trial. JAMA. 2010 Jan 6;303(1):37-46. doi: 10.1001/jama.2009.1911. Epub 2009 Dec 21.

  PMID: 20026597 BACKGROUND

• Brandriss MW, Schlesinger JJ, Walsh EE, Briselli M. Lethal 17D yellow fever encephalitis in mice. I. Passive protection by monoclonal antibodies to the envelope proteins of 17D yellow fever and dengue 2 viruses. J Gen Virol. 1986 Feb;67 ( Pt 2):229-34. doi: 10.1099/0022-1317-67-2-229.

  PMID: 3944585 BACKGROUND

• Monath TP. Yellow fever: an update. Lancet Infect Dis. 2001 Aug;1(1):11-20. doi: 10.1016/S1473-3099(01)00016-0.

  PMID: 11871403 BACKGROUND

• Measles vaccines: WHO position paper - April 2017. Wkly Epidemiol Rec. 2017 Apr 28;92(17):205-27. No abstract available. English, French.

  PMID: 28459148 BACKGROUND

Related Links

• WHO. Rubella vaccines: WHO position paper. Wkly Epidemiol Rec. WHO: WHO; 2020
• Organization CDSC. Summary of product characteristics Measles and Rubella Vaccine (Live) I.P. (Freeze Dried) 2024
• WHO. Yellow fever: WHO; 2023 \[updated 31 May 2023
• WHO. Yellow Fever Vaccines WHO web page: WHO
• WHO. Laboratory biosafety manual, 3rd edition. 2004
• Union E. Directive 2000/54/EC of the European Parliament and of the Council of 18 September 2000 on the protection of workers from risks related to exposure to biological agents at work (seventh individual directive within the meaning of Article 16(1) of

MeSH Terms

Conditions

Measles; Rubella; Yellow Fever

Interventions

Freeze Drying; Yellow Fever Vaccine

Condition Hierarchy (Ancestors)

Morbillivirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Rubivirus Infections; Togaviridae Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Cryopreservation; Tissue Preservation; Histocytological Preparation Techniques; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Preservation, Biological; Therapeutics; Investigative Techniques; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Central Study Contacts

Dr. Firdausi Qadri, PhD

CONTACT

88029827001-10; fqadri@icddrb.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is a prospective, randomized, parallel, three-arm, open-label, equivalence clinical trial of co-administration of MR vaccines (manufactured by Zydus Lifesciences Limited) and Yellow fever vaccine (WHO prequalified). The vaccine administration team will be un-blinded to the treatment assignment list. The vaccine administrator team members will not be involved in the evaluation of vaccine safety and laboratory analysis. The DSMB will be responsible for un-blinding the randomization number codes in the event of severe putative vaccine reactions. Otherwise, the codes will not be revealed until the end of the trial and until the computerized dataset has been frozen. If the intervention assignment is un-blinded, all study collaborators will be notified immediately. If deemed necessary, the DSMBs will recommend unblinding to the IRB and contact the study statistician responsible for providing information on the vaccine received by the individual in question.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomized, parallel, three-arm, open-label, equivalence clinical trial of co-administration of MR vaccines (manufactured by Zydus Lifesciences Limited) and Yellow fever vaccine (WHO prequalified) among healthy infants 9 to 12 months of age in Dhaka, Bangladesh who did not receive any of the aforementioned vaccines will be included in the study.

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: February 7, 2025
• Study Start: April 1, 2025
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)