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.: PACTR202407771418605 Date of Approval: 26/07/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title CVIA 106 - Phase 2/3 study of the EuBiologics pentavalent meningococcal ACWYX conjugate vaccine compared to MENVEO® or Nimenrix ® in healthy children through adults
Official scientific title A Phase 2/3 observer-blind, randomized, active-controlled study of the EuBiologics pentavalent meningococcal ACWYX conjugate vaccine (EuNmCV-5 Multi-dose) in healthy infants, toddlers, children, adolescents, and adults, to examine its safety, immunogenicity (including lot-to-lot consistency), and immunological non-inferiority when compared to MENVEO® or Nimenrix® as well as its non-interference with routinely co-administered vaccines
Brief summary describing the background and objectives of the trial Based on the promising safety and immunogenicity results from the Phase 1 study in Korean adults (EuVCT_MCV102, NCT05739292), this Phase 2/3 two-site clinical study in West Africa will include a progressive step-wise evaluation of the safety and immunogenicity profile of EuNmCV-5, covering the age range of 9 months to 29 years of age. This study will include a lot-to-lot comparison and an assessment of co administration with measles-rubella (MR) and yellow fever (YF) vaccines, as these are routinely administered within the EPI in this setting. Taken together, both studies should provide sufficient clinical data for marketing authorization and WHO prequalification of the vaccine for use in campaigns in individuals ≥ 1 and ≤ 29 years of age and in routine immunization programs at ≥ 9 months of age across the African meningitis belt.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Nervous System Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 20/08/2024
Actual trial start date
Anticipated date of last follow up 29/05/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 4236
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
CVIA 106 Sponsor
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 Permuted block randomization Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group EuNmCV5 2.5 mL/5 dose, 0.5 mL/dose 22 months Pentavalent meningococcal conjugate vaccine containing serogroups A, C, W, Y, and X (10 µg of A; 5 µg of C, W, Y, and X) conjugated to recombinant diphtheria toxin variant CRM197 and 2-PE in a multi-dose (2.5 mL/5 dose, 0.5 mL/dose) vial administered intramuscularly (IM) 2970
Control Group MENVEO 0.5 mL 22 months Quadrivalent meningococcal conjugate vaccine containing serogroups A, C, W, and Y conjugated to a modified diphtheria toxin (MenACWY-CRM) in a single-dose of 0.5 mL administered IM 846 Dose Comparison
Control Group Nimenrix 0.5mL 22 months Quadrivalent meningococcal conjugate vaccine containing serogroups A, C, W, and Y conjugated to TT (MenACWY TT) in a single-dose of 0.5 mL administered IM 420 Dose Comparison
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1.Male or female participants with the age at time of study vaccination 2.Participant informed consent or assent and/or parent and/or legal guardian informed consent: a.Children ≤ 17 years of age: Signed or fingerprinted or personally marked written informed consent obtained from parent and/or legal guardian b.Children ≥ 12 years of age in The Gambia and ≥ 13 years of age in Mali: Participant signed or fingerprinted or personally marked written informed assent c.Adults ≥ 18 years of age: Signed or fingerprinted or personally marked written informed consent Note: Participants who turn 18 years of age during the study period, will be required to provide informed consent 3.Children who complete their local EPI schedule: a.A birth dose of OPV is not required b.Cohort 2: Through and including 9 months of age (no MenAfriVac® dose) c.Cohort 4: Through and prior to 15 months of age (no MenAfriVac® dose and no 15+ months EPIs) d.Cohort 5: Through and prior to 9 months of age (no MenAfriVac® dose and no 9+ months EPIs) 4.Healthy, as defined by the absence of any clinically significant medical conditions 5.Participant and/or parent and/or legal guardian of the participant resides in the study site area, with no intent to move out during the study period, and is able and willing to adhere to all protocol requirements 6.Participant must be either of non-childbearing potential or, if of childbearing potential, not breastfeeding and not pregnant and must have been practicing adequate contraception for ≥ 2 months prior to study vaccination and agree to continue such precautions consistently through 2 months post study vaccination, as well as agree to not become pregnant through other means 7.Participant agrees not to enroll in another study of an investigational research agent 1.Acute illness at the time of study vaccination 2.Recorded fever/use of an antipyretic medication within 48 hours prior to study vaccination 3.Cohorts 1 and 2: a. Abnormal safety laboratory test value for age b. Laboratory confirmed HIV, chronic hepatitis B virus infection, and/or hepatitis C virus infection 4.Current/previous N. meningitidis 5.Household contact/intimate exposure to an individual with any laboratory confirmed N. meningitidis infection within 90 days prior to Screening 6.Administration of systemic antibiotic treatment within 3 days of study vaccination 7.Administration of any vaccine other than the study vaccines within 28 days prior to/after study vaccination 8. Participation in another investigational product clinical study within 90 days prior to enrollment in this study/receipt of any such investigational product other than the study vaccines within 30 days prior to administration of study vaccines/planned use during study 9.Receipt of immunoglobulins and/or any blood products within 90 days prior to study vaccination/planned administration during study 10.Confirmed/suspected/family history immunodeficiency of congenital or hereditary immunodeficiency 11.Prior use of or anticipated need of long-acting immunomodulating drug/chronic administration of high dose systemic corticosteroids during study 12.History of severe adverse/allergic reaction to any vaccine or any components of the study vaccines 13.Participant is an employee/close personal relation of any person employed by the Sponsor, PATH, the CRO, the PI, key study site personnel 14.Planned surgery during the study period that would require hospitalization, use of prohibited medication, or will interfere with follow-up visits 15.History of known disturbance of coagulation/blood disorder 16.Medical/psychiatric condition or laboratory abnormality that may increase the risk associated with study participation 17.Neurological disease/disorder Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Infant: 0 Month-23 Month,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 9 Month(s) 29 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 13/06/2024 The Gambia Government MRC Joint Ethics Committee
Ethics Committee Address
Street address City Postal code Country
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, Atlantic Boulevard, Fajara, PO Box 273, Banjul, The Gambia Banjul NA Gambia
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 20/05/2024 Ethics Committee EC of the Faculte de Medecine de Pharmacie et dOdonto Stomatologie FMPOS of the University of Science Technics and Technologies of Bamako
Ethics Committee Address
Street address City Postal code Country
Faculte de Medecine, de Pharmacie et deOdonto-Stomatologie Point G Bamako 1805 Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cohort 1 1. Number and severity of solicited AEs for 7 days following study vaccination (Day 8). 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination (Day 29). 3. Number, severity, and relatedness of SAEs for 168 days following study vaccination (Day 169). 1. Day 8 2. Day 29 3. Day 169
Secondary Outcome Cohort 1 1. GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineA and 28 days following study vaccination 2. Percentage of participants with seroresponse measured by rSBA against serogroups A, C, W, Y, and X at 28 days following study vaccination. (Seroresponse is defined as a rSBA titer ≥ 1:32 following study vaccination if the rSBA titer at Baseline was < 1:8; or a ≥ 4-fold increase over Baseline if the Baseline rSBA titer was ≥ 1:8.) 3. Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at Baseline and 28 days following study vaccination Day 29
Primary Outcome Cohort 2 1. Number and severity of solicited AEs for 7 days following study vaccination 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination 3. Number, severity, and relatedness of SAEs for 336 days following study vaccination 1. Day 8 2. Day 29 3. Day 337
Secondary Outcome Cohort 2 1. GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination 2. Percentage of participants with seroresponse measured by rSBA against serogroups A, C, W, Y, and X at 28 days following study vaccination. (Seroresponse is defined as a rSBA titer ≥ 1:32 following study vaccination if the rSBA titer at BaselineB was < 1:8; or a ≥ 4-fold increase over Baseline if the Baseline rSBA titer was ≥ 1:8.) 3. Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination Persistence outcomes 1.GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineB , and at 168 and 336 days following study vaccination (Days 169 and 337, respectively). 2.Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at 168 and 336 days following study vaccination (Days 169 and 337, respectively). Day 29
Primary Outcome Cohort 3 1. GMTs of rSBA against serogroups A, C, W, Y, and X at 28 days following study vaccination Day 29
Secondary Outcome Cohort 3 1. Number and severity of solicited AEs for 7 days following study vaccination 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination 3. Number, severity, and relatedness of SAEs for 168 days following study vaccination 4. Number, severity, and relatedness of SAEs for 336 days following study vaccination in a subset of children and adolescents ≥ 2 to ≤ 17 years of age 5. GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination 6. Percentage of participants with seroresponse, measured by rSBA against serogroups A, C, W, Y, and X at 28 days following study vaccination 7. Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination 8. In a subset of participants ≥ 2 and ≤ 29 years of age: o GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineB and at 168 days following study vaccination o Percentages of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, against serogroups A, C, W, Y, and X at at BaselineB and at 168 days following study vaccination 9. In a subset of children and adolescents ≥ 2 and ≤ 17 years of age: o GMTs of rSBA against serogroups A, C, W, Y, and X at at BaselineB and at 336 days following study vaccination o Percentages of participants with rSBA titer of ≥ 1:8 and ≥ 1:128 against serogroups A, C, W, Y, and X at at BaselineB and at 336 days following study vaccination 1. Day 8 2. Day 29 3. Day 169 4. Day 337 5. Day 29 6. Day 29 7. Day 29 8. Day 169 9. Day 337
Primary Outcome Cohort 4 1. The percentage of participants with rSBA titers ≥ 1:8 against serogroups A, C, W, Y, and X at 28 days following study vaccination Day 29
Secondary Outcome Cohort 4 1. Number and severity of solicited AEs for 7 days following study vaccination 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination 3. Number, severity, and relatedness of SAEs for 168 days following study vaccination 4. Percentage of participants with seropositive response for measles at 28 days following study vaccination. The seropositive response to measles vaccine is defined as anti-measles IgG concentration ≥ 200 mIU/mL. 5. Percentage of participants with seropositive response for rubella at 28 days following study vaccination. The seropositive response to rubella vaccine is defined as ≥ 10 IU/mL. 6. GMTs of rSBA against serogroups A, C, W, Y, and X at 28 days following study vaccination. 7. Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at and at 28 days following study vaccination. Persistence outcomes 1.GMTs of rSBA against serogroups A, C, W, Y, and X in a subset of participants at 168 days following study vaccination (Day 169) in a subset of participants. 2.Percentage with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at 168 days following study vaccination (Day 169) in a subset of participants. 1. Day 8 2. Day 29 3. Day 29 4. Day 29 5. Day 29 6. Day 29 7. Day 29
Primary Outcome Cohort 5 1. The percentage of participants with rSBA titers ≥ 1:8 against serogroups A, C, W, Y, and X at 28 days following study vaccination Day 29
Secondary Outcome Cohort 5 1. Number and severity of solicited AEs for 7 days following study vaccination 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination 3. Number, severity, and relatedness of SAEs for 168 days following study vaccination 4. Number, severity, and relatedness of SAEs for 336 days following study vaccination in a subset of participants 5. Percentage of participants with seropositive response for measles at 28 days following study vaccination. The seropositive response to measles vaccine is defined as anti-measles IgG concentration ≥ 200 mIU/mL. 6. Percentage of participants with seropositive response for rubella at 28 days following study vaccination. The seropositive response to rubella vaccine is defined as ≥ 10 IU/mL. 7. Percentage of participants with seroprotective titers for YF vaccine at 28 days following study vaccination. The seroprotective response to YF vaccine is defined as YF virus neutralizing antibody titers measured by PRNT50 ≥ 1:10. 8. GMTs of rSBA against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination. 9. Percentage of participants with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at BaselineB and 28 days following study vaccination. 10. In a subset of participants, GMTs of rSBA against serogroups A, C, W, Y, and X at 168 and 336 days following study vaccination. 11. In a subset of participants, percentage with rSBA titer of ≥ 1:8 and ≥ 1:128, respectively, against serogroups A, C, W, Y, and X at 168 and 336 days following study vaccination. 1. Day 8 2. Day 29 3. Day 169 4. Day 337 5. Day 29 6. Day 29 7. Day 29 8. Day 29 9. Day 29 10. Day 169 and Day 337 11. Day 169 and Day 137
Primary Outcome Cohort 6 1. Number and severity of solicited AEs for 7 days following study vaccination 2. Number, severity, and relatedness of unsolicited AEs for 28 days following study vaccination 3. Number, severity, and relatedness of SAEs for 168 days following study vaccination 1. Day 8 2. Day 29 3. Day 169
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine Atlantic Boulevard Fajara Banjul Gambia
Center for Vaccine Development Mali CVD Mali Ex-Institut Marchoux Avenue Mohamed VI Djicoroni Para Bamako 251 Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 5th Avenue North Seattle 98109 United States of America
Research Investment for Global Health Technology Foundation 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, Gangnma-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, Gangnma-gu Seoul 06026 Korea, Republic of Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries Christina Polyak cpolyak@path.org +12064738079 PATHs Center for Vaccine Innovation and Access 455 Massachusetts Ave Suite 1100
City Postal code Country Position/Affiliation
Washington 20001 United States of America Medical Officer
Role Name Email Phone Street address
Public Enquiries Niles Eaton neaton@path.org +12066963576 PATH Center for Vaccine Innovation and Access 2201 Westlake Avenue Suite 200
City Postal code Country Position/Affiliation
Seattle WA 98121 United States of America Clinical Research Manager
Role Name Email Phone Street address
Principal Investigator Ed Clarke ed.clarke@lshtm.ac.uk +2207039732 Medical Research Council MRC Unit The Gambia at London School of Hygiene and Tropical Medicine
City Postal code Country Position/Affiliation
Fajara Gambia Principal Investigator
Role Name Email Phone Street address
Principal Investigator Samba Sow ssow@cvd-mali.org +2232236031 Centre pour le Developpement des Vaccins du Mali CNAM Ex Institut Marchoux, Ministere de la Sante et de lHygiene Publique
City Postal code Country Position/Affiliation
Bamako Mali Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained through this study may be provided to qualified researchers with academic interest in Meningococcal disease. The individual participant data (IPD) that underlie the results reported in the article, after deidentification (text, tables, figures, and appendices) will be shared. Approval of the request and execution of all applicable agreements (i.e. a material transfer agreement) are prerequisites to the sharing of data with the requesting party. Study Protocol Beginning 3 months and ending 3 years following article publication. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact EuBiologics.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
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