Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202112680671189 Date of Approval: 24/12/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CVIA 092 Short Title: Phase 3 EuTCV Trial in Africa
Official scientific title A Phase 3 Multicenter, Observer Blind, Randomized, Controlled Study to Evaluate Safety (Ages 6 Months to 45 Years) and Non-inferiority (Ages 9-12 Months) of Multi-dose and Single-dose Vial Formulations of EuTCV (Vi-CRM197 Typhoid Conjugate Vaccine) against Typbar TCV® and Lot-to-Lot Consistency of the Immune Response (Ages 9-12 Months) to Multi-dose Vial Formulation EuTCV in Healthy African Participants
Brief summary describing the background and objectives of the trial Typhoid fever, an invasive bacterial infection caused by Salmonella enterica serovar typhi (S. typhi), remains an important public health problem. It is spread via contact with faeces-contaminated food, beverages and/or on occasion by direct contact with other infected humans. It may be transmitted via a food vehicle handled by an individual who is a chronic carrier of S. typhi - S. typhi is an obligate human pathogen; an effective vaccination program could lead to herd protection. WHO reiterated the global health importance of typhoid vaccination and recommends utilisation of parenteral Vi-conjugate vaccines. Multiple antibiotic resistance among typhoid strains and S. typhi is designated as an Antimicrobial Resistance (AMR) threat; accelerated vaccine development is needed. Primary: • Evaluate non-inferiority as measured by seroconversion rates of anti-Vi IgG antibody titers of single-dose and multi-dose vial formulations of EuTCV compared with Typbar TCV® at 28 days (in immunogenicity subset) • Evaluate safety of single-dose and multi-dose vial formulations of EuTCV and compare to that of Typbar TCV® Secondary: • Evaluate non-inferiority by anti-Vi IgG geometric mean titer (GMT) of single-dose and multi-dose vial formulations of EuTCV compared with Typbar TCV® at 28 days (in immunogenicity subset) • Evaluate immune persistence of single-dose and multi-dose vial formulations of EuTCV by anti-Vi IgG GMT and geometric mean fold-rise at 180 days post-vaccination from baseline (in immunogenicity subset) • Evaluate lot-to-lot consistency of multi-dose vial formulation of EuTCV by anti-VI IgG GMT at 28 days • Assess and compare immune response to the co-administered measles-rubella vaccine and yellow fever vaccine of infants receiving either single-dose or multi-dose vial formulations of EuTCV with those receiving Typbar TCV® (in immunogenicity subset) • Further assess immune response to co-administered MR vaccine, in terms of GMC (in immunogenicity subset)
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations,Paediatrics
Sub-Disease(s) or condition(s) being studied Typhoid fever
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 06/12/2021
Actual trial start date
Anticipated date of last follow up 03/04/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 3255
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://pactr.samrc.ac.za/
Secondary Ids Issuing authority/Trial register
Kenya Clinical Trials Registry
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group EuTCV is Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197 non preservative Single-dose vial EuTCV: 25 mcg / 0.5 mL dose purified Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197 Receive only one dose Each 0.5 mL dose contains 25 mcg purified Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197, non-preservative containing Typhoid Conjugate Vaccine (Manufacturer: EuBiologics Co., Ltd.) for intramuscular (IM) injection 1275
Experimental Group EuTCV is Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197 with preservative Multi-dose vial EuTCV: 2.5 mL-5 dose vial; each dose contains 25 mcg / 0.5 mL purified Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197 Receive only one dose Multi-dose vial EuTCV: 2.5 mL-5 dose vial, each 0.5 mL dose contains 25 mcg purified Vi polysaccharide of Salmonella typhi Ty2 conjugated to CRM197; 2-phenoxyethanol (2-PE) is included as a preservative (Manufacturer: EuBiologics Co., Ltd.) for IM injection 1650
Control Group Typbar TCV One dose Typbar TCV® 25 mcg / 0.5 mL purified Vi-Capsular Polysaccharide of S. typhi Ty2 conjugated to Tetanus Toxoid Receive only one dose Active-Comparator Vaccine: Typbar TCV®: each 0.5 mL dose contains 25 mcg purified Vi-Capsular Polysaccharide of S. typhi Ty2 conjugated to Tetanus Toxoid (Manufacturer: Bharat Biotech International Ltd.) for IM injection 330 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Male or female participants, ages 6 months to 45 years (all inclusive) 2. Healthy as defined by absence of clinically significant medical condition, either acute or chronic, as determined by medical history and clinical assessment 3. The participant him/herself (or his/her guardian or LAR) is informed and consents, and signs informed consent form. If the participant is above the age of assent per local ethics committee requirements, informed assent will also be sought. 4. Participants are able to follow the requirements of clinical trial protocol and intend to remain in the area during the study period 5. Individuals of childbearing capacity: Negative pregnancy test with understanding (through informed consent process) to not become pregnant during the study Specific for children: 1. 6–36-month-olds must have a weight for height Z score of ≥-2 at the time of randomization 2. Infants must have been born >36 weeks gestation 3. Must have completed all age-appropriate recommended EPI vaccinations at time of randomization -Participation in research involving another IP during the 30 days before planned first vaccination or concurrently participating in another clinical study -History of major congenital abdominal disorders, intussusception, abdominal surgery, or other congenital disorder or presence of significant medical condition -Clinical evidence of gastrointestinal illness and acute disease (a temporary exclusion) -Known or suspected impairment of immunological function based on medical history and examination. Known history of immune function disorders incl immunodeficiency disease or chronic systemic steroid use, cytotoxic or immunosuppressive drugs -Breastfeeding, pregnancy, planning pregnancy during the study, or unwilling to use adequate contraception -History of uncontrolled coagulopathy or blood disorders -Presence of known systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) -Known history of administration of blood or blood-derived products in the past 90 days -Previously ascertained or suspected disease caused by S. typhi -Household contact with and/or intimate exposure to individual with laboratory-confirmed S. typhi -Have received a dose of Typhoid-containing vaccine within the last 10 years -Already immunised with any licensed vaccine within 4 weeks prior to enrolment/vaccination -Have experienced transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or typhoid -Known hypersensitivity to any component of the study vaccines -Clinically significant screening laboratory value -Acute illness, infectious disease, or fever within 3 days and/or acute illness requiring antibiotic or antiviral within past 7 days -Not be able to comply with any of the protocol required procedures Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 6 Month(s) 45 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/09/2022 KEMRI IRB Kenya Medical Research Institute Scientific and Ethics Review Unit KEMRI SERU
Ethics Committee Address
Street address City Postal code Country
PO Box 54840 00200 off Mbagathi Road Nairobi 00100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/06/2022 WRAIR Walter Reed Army Institute of Research
Ethics Committee Address
Street address City Postal code Country
503 Robert Grant Avenue Silver Spring MD 20910 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 07/12/2021 CNERS Comite National dEthique pour Ia Recherche en Sante
Ethics Committee Address
Street address City Postal code Country
Ministere de la Sante et de lAction Sociale, Aime Cesaire, Fann Residence Dakar 12500 Senegal
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 29/06/2022 WCG Institutional Review Board IRB
Ethics Committee Address
Street address City Postal code Country
1019 39th Ave., SE, Suite 120 Puyallup WA 98374 United States of America
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 03/08/2022 National Commission for Science Technology and Innovation NACOSTI
Ethics Committee Address
Street address City Postal code Country
off Waiyaki Way, Upper Kabete Nairobi 00100 Kenya
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 01/09/2022 Pharmacy and Poisons Board MOH
Ethics Committee Address
Street address City Postal code Country
Pharmacy and Poisons Board Hourse, Lenana Road Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Immunogenicity: Seroconversion rates (≥4-fold rise from baseline) of anti-Vi IgG ELISA titers at 28 days after vaccination of EuTCV multi-dose vial, EuTCV single-dose vial, or Typbar TCV® (immunogenicity subset) 28 days after vaccination
Primary Outcome Safety: Proportion of solicited local and systemic adverse events; o Local: pain, tenderness, erythema/redness, swelling/induration, pruritus, and abscess o Systemic (adapted to each age group): fever, lethargy, irritability, nausea/vomiting, arthralgia, diarrhoea, drowsiness, loss of appetite, chills, headache, fatigue, myalgia, persistent crying and acute allergic reaction. During 7 days after vaccination
Primary Outcome Safety: Proportion of unsolicited AEs Within 28 days after vaccination
Primary Outcome Safety: Proportion of SAEs throughout the study Through 180 days after vaccination
Secondary Outcome GMTs of anti-Vi IgG 28 days after vaccination of EuTCV single-dose vial, EuTCV multi-dose vial, or Typbar TCV® (immunogenicity subset) Day 29
Secondary Outcome GMTs and GMFR from baseline of Anti-Vi serum IgG at 180 days post-vaccination either multi-dose and single-dose formulations of EuTCV or Typbar TCV® (immunogenicity subset) Day 181
Secondary Outcome GMTs of anti-Vi ELISA 28 days following a single dose of multi-dose vial EuTCV for the assessment of consistency of response across three lots of vaccine (immunogenicity subset) Day 29
Secondary Outcome Percentage of participants with measles IgG seroconversion by ELISA 28 days following vaccination with either single-dose vial and multi-dose vial formulations of EuTCV or Typbar TCV®. (Measles seroconversion in initially seronegative infants will be defined as concentrations ≥200 mlU/mL) (immunogenicity subset) Day 29
Secondary Outcome Percentage of participants with rubella IgG seroconversion by ELISA 28 days following vaccination with either single-dose vial and multi-dose vial formulations of EuTCV or Typbar TCV®. (Rubella seroconversion in initially seronegative infants will be defined as concentrations ≥10 lU/mL) (immunogenicity subset) Day 29
Secondary Outcome Percentage of participants with yellow fever neutralizing antibody seroconversion 28 days following vaccination with either single-dose vial and multi-dose vial formulations of EuTCV or Typbar TCV® (YFV seroconversion is defined as a reciprocal 50% plaque reduction neutralization titer (PRNT50) of ≥10 among those participants negative (PRNT50< 10) at baseline) (immunogenicity subset) Day 29
Secondary Outcome Measles IgG GMC 28 days following vaccination with either single-dose vial and multi-dose vial formulations of EuTCV or Typbar TCV® (immunogenicity subset) Day 29
Secondary Outcome Rubella IgG GMCs 28 days following vaccination with either single-dose vial and multi-dose vial formulations of EuTCV or Typbar TCV® (immunogenicity subset) Day 29
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya Medical Research Institute Kericho Hospital Road, PO Box 1357 Kericho 20200 Kenya
IRESSEF Institut de Recherche en Sante de Surveillance Epidemiologique et de Formation Arrondissement 4 Rue 2 D1 Pole Urbain de Diamniado Dakar BP 7325 Senegal
FUNDING SOURCES
Name of source Street address City Postal code Country
Research Investment for Global Health Technology RIGHT Fund and TBD International Vaccine Institute, 2nd Floor, SNU, Research Park, 1 Gwanak-ro, Gwanak-gu Seoul 08826 Korea, Republic of
EuBiologics Co. Ltd 8F Seongdo B/D, 207 Dosan-daero, Sinsa-dong ,Gangnam-gu Seoul 06026 Korea, Republic of
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor EuBiologics Co Ltd 8F Seongdo B/D, 207 Dosan-daero, Sinsa-dong ,Gangnam-gu Seoul 06026 Korea, Republic of Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
PATH Center for Vaccine Innovation and Access CVIA 455 Massachusetts Avenue, Suite 1000 Washington DC 20001 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Patricia Njuguna pnjuguna@path.org +254101833063 PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road
City Postal code Country Position/Affiliation
Nairobi 00100 Kenya PATH Medical Officer
Role Name Email Phone Street address
Public Enquiries Niles Eaton neaton@path.org +12066963576 PATH Center for Vaccine Innovation and Access CVIA 2201 Westlake Avenue, Suite 200 Seattle, WA 98121
City Postal code Country Position/Affiliation
Seattle WA 98121 United States of America Clinical Operations Specialist and Clinical Research Manager
Role Name Email Phone Street address
Principal Investigator Lucy C Koech Lucy.koech@usamru-k.org +254522036100 Kenya Medical Research Institute Kericho Hospital Road PO Box 1357
City Postal code Country Position/Affiliation
Kericho 20200 Kenya Principal Investigator
Role Name Email Phone Street address
Principal Investigator Pierre B Ndiaye birahimpierre.ndiaye@iressef.org +221776389908 IRESSEF Institut de Recherche en Sante, de Surveillance Epidemiologique et de Formations, Arrondissement 4 Rue 2 D1 Pole Urbain de Diamniado
City Postal code Country Position/Affiliation
Dakar BP7325 Senegal Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The results of the trial will be shared with trial participants in a manner clearly stipulated by the protocol team. The Study Report will also be made available in line with the country, international and sponsor regulations. Clinical Study Report Three (3) years Final Study Report from protocol team
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Not available No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 22/12/2021 Updated FALSE, CNERS Comite National dEthique pour Ia Recherche en Sante , Ministere de la Sante et de lAction Sociale, Aime Cesaire, Fann Residence, Dakar, None, Senegal, 10 Aug 2021, , +221773614212, ousmanediouf7@gmail.com, TRUE, CNERS Comite National dEthique pour Ia Recherche en Sante , Ministere de la Sante et de lAction Sociale, Aime Cesaire, Fann Residence, Dakar, None, Senegal, 10 Aug 2021, 07 Dec 2021, +221773614212, ousmanediouf7@gmail.com, 16067_13477_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 22/12/2021 post code included TRUE, CNERS Comite National dEthique pour Ia Recherche en Sante , Ministere de la Sante et de lAction Sociale, Aime Cesaire, Fann Residence, Dakar, None, Senegal, , 07 Dec 2021, +221773614212, ousmanediouf7@gmail.com, 16067_13477_4737.pdf TRUE, CNERS Comite National dEthique pour Ia Recherche en Sante , Ministere de la Sante et de lAction Sociale, Aime Cesaire, Fann Residence, Dakar, 12500, Senegal, , 07 Dec 2021, +221773614212, ousmanediouf7@gmail.com, 16067_13477_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 05/01/2022 Medical Officer needed to be updated from Rashan Ederm to Patricia Njuguna. Scientific Enquiries, Rahsan, Erdem, Dr., rerdem@path.org, , +12025404546, PATH Center for Vaccine Innovation and Access, CVIA, 455 Massachusetts Avenue, Suite 1000 Washington, DC 20001 USA, Washington DC, 20001, United States of America, PATH Medical Officer Scientific Enquiries, Patricia , Njuguna, Dr., pnjuguna@path.org, , +254721833063, PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road, Nairobi, , Kenya, PATH Medical Officer
Section Name Field Name Date Reason Old Value Updated Value
Funding Source FundingSources List 05/01/2022 Updated EuBiologics Co. Ltd, 125, Wonmudong-gil, Dongsan-myeon, Chuncheon-si, Gangwon-do, Chuncheon si, , China, Commercial Sector / Industry, EuBiologics Co. Ltd, 8F Seongdo B/D, 207 Dosan-daero, Sinsa-dong ,Gangnam-gu, Seoul, 06026, Korea, Republic of, Commercial Sector / Industry,
Section Name Field Name Date Reason Old Value Updated Value
Sponsors Sponsors List 05/01/2022 Update EuBiologics Co Ltd, R D Center 125 Wonmudong gil Dongsan myeon Chuncheon si Gangwon do Korea, Chuncheon si, , China, Primary Sponsor, Commercial Sector/Industry, EuBiologics Co Ltd, 8F Seongdo B/D, 207 Dosan-daero, Sinsa-dong ,Gangnam-gu, Seoul, 06026, Korea, Republic of, Primary Sponsor, Commercial Sector/Industry,
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 01/06/2022 IRESSEF site in Senegal started recruitment on 04-May-2022. Screening started on 04-May-2022 and first enrolment was on 10-May-2022. Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 16/09/2022 postal code for Nairobi added Scientific Enquiries, Patricia , Njuguna, Dr., pnjuguna@path.org, , +254721833063, PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road, Nairobi, , Kenya, PATH Medical Officer Scientific Enquiries, Patricia , Njuguna, Dr., pnjuguna@path.org, , +254721833063, PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road, Nairobi, 00100, Kenya, PATH Medical Officer
Section Name Field Name Date Reason Old Value Updated Value
Contact People Contacs List 16/09/2022 Telephone number updated Scientific Enquiries, Patricia , Njuguna, Dr., pnjuguna@path.org, , +254721833063, PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road, Nairobi, 00100, Kenya, PATH Medical Officer Scientific Enquiries, Patricia , Njuguna, Dr., pnjuguna@path.org, , +254101833063, PATH Center for Vaccine Innovation and Access, CVIA, ACS Plaza, 4th floor, Lenana Road, Nairobi, 00100, Kenya, PATH Medical Officer
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/09/2022 Approval letter received FALSE, WRAIR Walter Reed Army Institute of Research , 503 Robert Grant Avenue, Silver Spring , MD 20910, United States of America, 14 Sep 2021, , +13013199000, usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil, TRUE, WRAIR Walter Reed Army Institute of Research , 503 Robert Grant Avenue, Silver Spring , MD 20910, United States of America, 14 Sep 2021, 01 Jun 2022, +13013199000, usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil, 16067_13475_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/09/2022 Nairobi postal code added. SERU Approval letter received FALSE, KEMRI IRB Kenya Medical Research Institute Scientific and Ethics Review Unit KEMRI SERU, PO Box 54840 00200 off Mbagathi Road, Nairobi, None, Kenya, 09 Jul 2021, , +254722205901, seru@kemri.org, TRUE, KEMRI IRB Kenya Medical Research Institute Scientific and Ethics Review Unit KEMRI SERU, PO Box 54840 00200 off Mbagathi Road, Nairobi, 00100, Kenya, 09 Jul 2021, 01 Sep 2022, +254722205901, seru@kemri.org, 16067_13474_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/09/2022 Approval letter received from WCG IRB (tracing its roots to the founding of Western Institutional Review Board (WIRB) and integration of WIRB with four leading independent IRBs in 2020 — Copernicus Group IRB, New England IRB, Aspire IRB, and Midlands IRB TRUE, WCG Institutional Review Board IRB, 1019 39th Ave., SE, Suite 120, Puyallup, WA 98374, United States of America, , 29 Jun 2022, +18558182289, clientcare@wcgirb.com, 16067_18658_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/09/2022 Research License received - Ref 175060 TRUE, National Commission for Science Technology and Innovation NACOSTI, off Waiyaki Way, Upper Kabete, Nairobi, 00100, Kenya, , 03 Aug 2022, +25204007000, dg@nacosti.go.ke, 16067_18659_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 16/09/2022 Regulatory Authority / MOH approval TRUE, Pharmacy and Poisons Board MOH, Pharmacy and Poisons Board Hourse, Lenana Road , Nairobi, 00100, Kenya, , 01 Sep 2022, +25202716905, info@pharmacyboardkenya.org, 16067_18660_4737.pdf