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.: PACTR202008675647876 Date of Approval: 05/08/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Phase 3 Trial to Study Alternate 2-Dose Regimens of a Bivalent HPV Vaccine (Cecolin®) in Young Girls
Official scientific title A Phase 3 Randomized, Active-Comparator Controlled, Open-Label Trial to Evaluate the Immunogenicity and Safety of Alternate Two-Dose Regimens of a Bivalent Human Papillomavirus (HPV) Vaccine (Cecolin®) Compared to a Licensed Quadrivalent HPV Vaccine (Gardasil®) in Healthy 9-14 Year-Old Girls in Low and Low-Middle Income Countries
Brief summary describing the background and objectives of the trial This planned randomized controlled trial will evaluate a bivalent HPV vaccine, Cecolin®, in alternate 2-dose regimens, compared to an established HPV vaccine. Gardasil® used as the comparator vaccine, as this vaccine is most widely used in low- and low-middle income countries. This randomized, active-comparator controlled, open-label study will enroll total of approximately 1025 girls aged 9 to 14 years, in one country in Africa (Ghana) and one country in South/Southeast Asia (Bangladesh). Subjects will be randomized 1:1:1:1:1 to receive Cecolin® at 0 and 6 months, 0 and 12 months, or 0 and 24 months, Gardasil® at 0 and 6 months, or Gardasil® at 0 months and Cecolin® at 24 months. For each arm, blood will be collected for immunologic testing at baseline and one month following second dose. Additional blood collections will occur immediately prior to the administration of the second dose, as well as at additional later time points, for immunobridging to other published and ongoing trials. The study also aims to evaluate the performance of a mixed arm (group 5) of Gardasil® followed by Cecolin® and collect data on effects of interchangeability. Girls of target age will be identified, and their parents contacted to attend an informational session for individual discussion, informed consent, assent and randomization. The study will be conducted by the research groups in International Centre for Diarrhoeal Disease Research (ICDDR), Bangladesh and Malaria Research Center (MRC) in Ghana.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/12/2020
Actual trial start date 15/03/2021
Anticipated date of last follow up 15/01/2024
Actual Last follow-up date 14/12/2023
Anticipated target sample size (number of participants) 1025
Actual target sample size (number of participants) 1025
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Central randomisation by phone/fax Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Cecolin Two doses of Cecolin® given at 0 and 6 months 24 months after first dose Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine 205
Experimental Group Cecolin Two doses of Cecolin® given at 0 and 12 months 1 month post dose 2 Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine 205
Experimental Group Cecolin Two doses of Cecolin® given at 0 and 24 months 1 month post dose 2 Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine 205
Control Group Gardasil Two doses of Gardasil® given at 0 and 6 months 24 months post dose 1 Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine 205 Active-Treatment of Control Group
Experimental Group Gardasil and Cecolin One dose of Gardasil® at 0 months and one dose of Cecolin® at 24 months 1 month post dose 2 Cecolin®: Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine Gardasil®: Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine 205
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Healthy female between the ages of 9 - 14 years. (all inclusive) at time of enrollment 2. Ability and willingness to provide parental consent and, if applicable based on local in-country regulations, participant assent 3. Parent/LAR provides informed consent 4. Anticipated ability and willingness to complete all study visits and evaluations 5. Living within the catchment area of the study without plans to move during the conduct of the study 1. Presence of fever or acute disease on the day of vaccination (oral or axillary temperature ≥38˚ C) 2. If participants have childbearing potential, must not be breastfeeding or confirmed pregnant 3. Receipt of an investigational product within 30 days prior to randomization 4. Receipt of blood and/or blood products (including immunoglobulin) 3 months prior to any dose of vaccination or blood sampling 5. Receipt of a live virus vaccine (varicella virus containing vaccine, any measles, mumps, or rubella virus containing vaccine such as MMR, or yellow fever vaccine but not including live attenuated influenza virus vaccine) 4 weeks prior and after each dose of HPV vaccine 6. History of any physical, mental, or developmental disorder that may hinder a participant's ability to comply with the study requirements 7. History of malignancy or confirmed or suspected immunodeficient condition such as HIV infection 8. Receipt of or history of receipt of any medications or treatments that affect the immune system 9. Allergies to any components of the vaccine 10. Current or former participation in HPV vaccine related research. 11. Prior receipt of an investigational or licensed HPV vaccine 12. Any other condition(s) that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocolmply with the protocol Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year 9 Year(s) 14 Year(s) Female
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 27/01/2021 Ghana Health Service Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
P. O. Box MB 191 Accra 0000 Ghana
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 15/01/2021 Committee on Human Research Publication and Ethics
Ethics Committee Address
Street address City Postal code Country
KNUST, Accra Rd, Kumasi Kumasi 0000 Ghana
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 01/09/2020 Ethical Review Committee
Ethics Committee Address
Street address City Postal code Country
Mohakhali Dhaka 1212 Bangladesh
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 30/12/2020 Western IRB
Ethics Committee Address
Street address City Postal code Country
1019 39th Avenue SE Suite 120 Puyallup 98374 United States of America
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Anti-HPV 16 and 18 IgG antibody geometric mean concentration (GMC), measured by enzyme-linked immunosorbent assay (ELISA) one month after the second dose on Month 7 (for the 0, 6-month arms), Month 13 (for the 0, 12-month arm) or Month 25 (for the 0, 24-month arm) following vaccination One month after the second dose given at 6 months, 12 months and 24 months
Secondary Outcome Anti-HPV 16 and 18 serum neutralizing antibody geometric mean titer measured by PBNA compared to ELISA at all time points (in a representative subset) Baseline, prior to second dose, one month post second dose and 24 months post first dose
Secondary Outcome Seroconversion rate, defined as a 4-fold rise in anti-HPV 16 and 18 IgG antibody as measured by ELISA, at baseline and one month following the last dose One month after second dose
Secondary Outcome Anti-HPV16 and 18 IgG antibody GMC measured by ELISA one month following the last dose of the Gardasil® 0-6 month two dose regimen and the Gardasil®-Cecolin® 0-24 month two dose regimen One month after second dose
Secondary Outcome Anti-HPV16 and 18 IgG antibody GMC measured by ELISA 24 months following the first dose of the Gardasil® 0-6 month two dose regimen and the Cecolin® 0-6 month two dose regimen 24 months after the first dose
Secondary Outcome Number of subjects in each study arm reporting solicited adverse events within 7 days after each dose, Number of subjects in each study arm reporting unsolicited adverse events within one month after each dose, Number of subjects in each study arm reporting serious adverse events (SAEs) occurring at any time throughout study participation Solicited AEs- 7 days post vaccination, unsolicited AEs - one month after each dose and SAEs-throughout the study period
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
International Centre for Diarrhoeal Disease Research 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali Dhaka 1212 Bangladesh
Malaria Research Centre Agogo Presbyterian Hospital P.O. Box 27 Agogo Ghana
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation 500 Fifth Avenue North Seattle United States of America
KfW Bankengruppe Palmengartenstrasse 5-9 D-60325 Frankfurt am Main Frankfurt Germany
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor PATH 2201 Westlake Ave Seattle 98121 United States of America Other Collaborative Groups
COLLABORATORS
Name Street address City Postal code Country
International Centre for Diarrhoeal Disease Research 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali Dhaka 1212 Bangladesh
Malaria Research Centre Agogo Presbyterian Hospital KNUST Post Office PO Box 27 Agogo Ghana
Frederick National Laboratory for Cancer Research Leidos Biomedical Research Inc P.O. Box B Frederick 21702 United States of America
The Emmes Company LLC 401 N. Washington St., Suite 700 Rockville 20850 United States of America
Xiamen Innovax Biotech Co. Ltd No. 52, Shanbianhong East Road, Haicang District, Xiamen City, Fujian Province Xiamen City 361027 China
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Khalequz Zaman kzaman@icddrb.org 0088029827001 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali
City Postal code Country Position/Affiliation
Dhaka 1212 Bangladesh Senior Scientist and Epidemiologist Enteric and Respiratory Infections
Role Name Email Phone Street address
Principal Investigator Tsiri Agbenyega tsiri@ghana.com 00233208113848 KNUST Post Office P.O. Box 27
City Postal code Country Position/Affiliation
Agogo 00000 Ghana Professor
Role Name Email Phone Street address
Scientific Enquiries Niranjan Bhat nbhat@path.org 0012062258386 2201 Westlake Ave Suite 200
City Postal code Country Position/Affiliation
Seattle United States of America Senior Medical Officer
Role Name Email Phone Street address
Public Enquiries Niranjan Bhat nbhat@path.org 12062258386 2201 Westlake Ave Suite 200
City Postal code Country Position/Affiliation
Seattle United States of America Senior Medical Officer
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Summary results for primary and secondary objectives. Statistical Analysis Plan,Study Protocol Within 12 months of completion of study Researchers who provide a methodologically sound proposal may be provided access after Sponsor permission.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Yes 05/12/2024
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 05/12/2024
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Public title 05/08/2020 edit Phase 3 Trial to Study Alternate 2-Dose Regimens of a Bivalent HPV Vaccine (Cecolin®) in Young Girls Phase 3 Trial to Study Alternate 2-Dose Regimens of a Bivalent HPV Vaccine (Cecolin®) in Young Girls
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Trial description 05/08/2020 edit This planned randomized controlled trial will evaluate a bivalent HPV vaccine, Cecolin®, in alternate 2-dose regimens, compared to an established HPV vaccine. Gardasil® used as the comparator vaccine, as this vaccine is most widely used in low- and low-middle income countries. This randomized, active-comparator controlled, open-label study will enroll total of approximately 1025 girls aged 9 to 14 years, in one country in Africa (Ghana) and one country in South/Southeast Asia (Bangladesh). Subjects will be randomized 1:1:1:1:1 to receive Cecolin® at 0 and 6 months, 0 and 12 months, or 0 and 24 months, Gardasil® at 0 and 6 months, or Gardasil® at 0 months and Cecolin® at 24 months. For each arm, blood will be collected for immunologic testing at baseline and one month following second dose. Additional blood collections will occur immediately prior to the administration of the second dose, as well as at additional later time points, for immunobridging to other published and ongoing trials. The study also aims to evaluate the performance of a mixed arm (group 5) of Gardasil® followed by Cecolin® and collect data on effects of interchangeability. Girls of target age will be identified, and their parents contacted to attend an informational session for individual discussion, informed consent, assent and randomization. The study will be conducted by the research groups in icddr,b in Bangladesh and Malaria Research Center (MRC) in Ghana. This planned randomized controlled trial will evaluate a bivalent HPV vaccine, Cecolin®, in alternate 2-dose regimens, compared to an established HPV vaccine. Gardasil® used as the comparator vaccine, as this vaccine is most widely used in low- and low-middle income countries. This randomized, active-comparator controlled, open-label study will enroll total of approximately 1025 girls aged 9 to 14 years, in one country in Africa (Ghana) and one country in South/Southeast Asia (Bangladesh). Subjects will be randomized 1:1:1:1:1 to receive Cecolin® at 0 and 6 months, 0 and 12 months, or 0 and 24 months, Gardasil® at 0 and 6 months, or Gardasil® at 0 months and Cecolin® at 24 months. For each arm, blood will be collected for immunologic testing at baseline and one month following second dose. Additional blood collections will occur immediately prior to the administration of the second dose, as well as at additional later time points, for immunobridging to other published and ongoing trials. The study also aims to evaluate the performance of a mixed arm (group 5) of Gardasil® followed by Cecolin® and collect data on effects of interchangeability. Girls of target age will be identified, and their parents contacted to attend an informational session for individual discussion, informed consent, assent and randomization. The study will be conducted by the research groups in International Centre for Diarrhoeal Disease Research (ICDDR), Bangladesh and Malaria Research Center (MRC) in Ghana.
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 19/03/2021 Confirming first site activation took place on 14Mar2021. 14 Mar 2021
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Actual trial start date 08/10/2021 Per sponsor request. 14 Mar 2021 15 Mar 2021
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Anticipated date of last follow up 08/10/2021 Per sponsor request. 29 Sep 2023 15 Jan 2024
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Completion date 03/01/2024 LSLV accomplished 14 Dec 2023
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Final no of participants 03/01/2024 LSLV accomplished 1025
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 19/03/2021 First site was activated. Not yet recruiting Recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 28/02/2022 The study has enrolled all planned participants and is in the follow-up phase. Recruiting Active, not recruiting
Section Name Field Name Date Reason Old Value Updated Value
Trial Information Recruitment status 03/01/2024 LSLV accomplished Active, not recruiting Completed
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Updating the record as study was approved in January 2021. FALSE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, 12 Aug 2020, , 0503539896, ethics.research@ghsmail.org, TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, 12 Aug 2020, 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Adding the conditional approval for initial IRB review. TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Uploading all current approvals as a single PDF. TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/10/2021 Put files in sequential order. TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf TRUE, Ghana Health Service Ethics Review Committee , P. O. Box MB 191, Accra, 0000, Ghana, , 27 Jan 2021, 0503539896, ethics.research@ghsmail.org, 12224_11580_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/10/2021 Put files in sequential order. TRUE, Committee on Human Research Publication and Ethics , KNUST, Accra Rd, Kumasi, Kumasi, 0000, Ghana, , 15 Jan 2021, 0205453785, chrpe.knust.kath@gmail.com, 12224_11581_4737.pdf TRUE, Committee on Human Research Publication and Ethics , KNUST, Accra Rd, Kumasi, Kumasi, 0000, Ghana, , 15 Jan 2021, 0205453785, chrpe.knust.kath@gmail.com, 12224_11581_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Updating record with initial IRB approval date and approval letters. FALSE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, 17 Jul 2020, , +88029827084, info@icddrb.org, TRUE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, 17 Jul 2020, 01 Sep 2020, +88029827084, info@icddrb.org, 12224_11582_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/10/2021 Put files in sequential order. TRUE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, , 01 Sep 2020, +88029827084, info@icddrb.org, 12224_11582_4737.pdf TRUE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, , 01 Sep 2020, +88029827084, info@icddrb.org, 12224_11582_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/10/2021 Updating the initial approval to be the original form. TRUE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, , 01 Sep 2020, +88029827084, info@icddrb.org, 12224_11582_4737.pdf TRUE, Ethical Review Committee, Mohakhali, Dhaka, 1212, Bangladesh, , 01 Sep 2020, +88029827084, info@icddrb.org, 12224_11582_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Updating with initial IRB approval date and attaching the approval letters. FALSE, Western IRB, 1019 39th Avenue SE Suite 120 , Puyallup, 98374, United States of America, 31 Aug 2020, , 0013602522500, clientservices@wirb.com, TRUE, Western IRB, 1019 39th Avenue SE Suite 120 , Puyallup, 98374, United States of America, 31 Aug 2020, 30 Dec 2020, 0013602522500, clientservices@wirb.com, 12224_11586_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 26/10/2021 Put files in sequential order. TRUE, Western IRB, 1019 39th Avenue SE Suite 120 , Puyallup, 98374, United States of America, , 30 Dec 2020, 0013602522500, clientservices@wirb.com, 12224_11586_4737.pdf TRUE, Western IRB, 1019 39th Avenue SE Suite 120 , Puyallup, 98374, United States of America, , 30 Dec 2020, 0013602522500, clientservices@wirb.com, 12224_11586_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Ethics Ethics List 14/10/2021 Updating to include the approvals. FALSE, Committee on Human Research Publication and Ethics , KNUST, Accra Rd, Kumasi, Kumasi, 0000, Ghana, 12 Aug 2020, , 0205453785, chrpe.knust.kath@gmail.com, TRUE, Committee on Human Research Publication and Ethics , KNUST, Accra Rd, Kumasi, Kumasi, 0000, Ghana, 12 Aug 2020, 15 Jan 2021, 0205453785, chrpe.knust.kath@gmail.com, 12224_11581_4737.pdf
Section Name Field Name Date Reason Old Value Updated Value
Reporting Results Available 05/12/2024 Final results available No Yes
Section Name Field Name Date Reason Old Value Updated Value
Reporting Result Summary Pdf file1 05/12/2024 Final study results 12224_10500_1045.pdf