Clinical trial NCT04508309: Phase 3 Trial of a Bivalent Human Papilloma Virus (HPV) Vaccine (Cecolin®) in Young Girls
Official title: Phase 3 Randomized, Active-Comparator Controlled, Open-Label Trial to Evaluate the Immunogenicity & Safety of Alternate 2-Dose Regimens of Cecolin® Compared to Gardasil® in 9-14 Year-Old Girls in Low and Low-Middle Income Countries
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancer
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: International Centre for Diarrhoeal Disease Research, Bangladesh
name: Malaria Research Centre, Agogo Presbyterian Hospital, Ghana
name: Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., USA
name: The Emmes Company, LLC
name: Xiamen Innovax Biotech Co., Ltd
First posted: 2020-08-11
Enrollment: 1025
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomized controlled trial will evaluate a bivalent HPV vaccine, Cecolin®, in alternate 2-dose regimens, compared to an established HPV vaccine. Gardasil® will be used as the comparator vaccine, as this vaccine is most widely used in low- and low-middle income countries.

Detailed description: 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). Participants 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, Bangladesh (icddr,b) in Bangladesh and the Malaria Research Center (MRC) in Ghana.

Eligibility criteria: Inclusion Criteria:

1. Healthy (determined by investigator's assessment following medical history and physical examination, laboratory evaluation could be performed at the investigator's discretion) 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/Legally Acceptable Representative 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

Exclusion Criteria:

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 Measles, Mumps, and Rubella (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. Any malignancy or confirmed or suspected immunodeficient condition such as HIV infection, based on medical history and physical examination
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 protocol

Primary outcomes:
measure: Geometric Mean Concentration (GMC) of Anti-HPV-16 Immunoglobulin G (IgG) Antibodies One Month After the Second Dose
timeFrame: One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).
measure: Geometric Mean Concentration of Anti-HPV-18 Immunoglobulin G Antibodies One Month After the Second Dose
timeFrame: One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).
Secondary outcomes:
measure: Geometric Mean Titer (GMT) of Anti-HPV-16 Neutralizing Antibodies
timeFrame: Prior to 2nd dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5), one month post 2nd dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5) and 18 months after 2nd dose for Groups 1 and 4 only
measure: Geometric Mean Titer (GMT) of Anti-HPV-18 Neutralizing Antibodies
timeFrame: Prior to 2nd dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5), one month post 2nd dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5) and 18 months after 2nd dose for Groups 1 and 4 only
measure: Seroconversion Rate For HPV-16 One Month After the Second Dose
timeFrame: Baseline and one month after second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).
measure: Seroconversion Rate For HPV-18 One Month After the Second Dose
timeFrame: Baseline and one month after second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).
measure: GMC of Anti-HPV-16 IgG Antibodies One Month After the Second Dose: Comparison of Gardasil/Cecolin Mixed Dose With Gardasil 2-dose Regimen
timeFrame: One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5).
measure: GMC of Anti-HPV-18 IgG Antibodies One Month After the Second Dose: Comparison of Gardasil/Cecolin Mixed Dose With Gardasil 2-dose Regimen
timeFrame: One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5).
measure: GMC of Anti-HPV-16 IgG Antibodies 18-Months After Second Dose
timeFrame: 18 months after the second dose (Month 24)
measure: GMC of Anti-HPV-18 IgG Antibodies 18-Months After Second Dose
timeFrame: 18 months after the second dose (Month 24)
measure: Number of Participants With Solicited Adverse Events
timeFrame: For 30 minutes after each vaccination and for up to 7 days after each vaccination
measure: Number of Participants With Unsolicited Adverse Events
timeFrame: For 30 days after each dose (Month 0 (all groups), Month 6 (Groups 1 and 4), Month 12 (Group 2), and Month 24 (Groups 3 and 5)
measure: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From first dose through the end of study (up to 730 days for Groups 1 and 4, 395 days for Group 2, and 760 days for Groups 3 and 5)
Other outcomes:
measure: GMC of Anti-HPV-16 IgG Antibodies Prior to the Second Dose
timeFrame: Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5).
measure: GMC of Anti-HPV-18 IgG Antibodies Prior to the Second Dose
timeFrame: Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5).
Locations:
city: Dhaka
country: Bangladesh
facility: International Centre for Diarrhoeal Disease Research
city: Agogo
country: Ghana
facility: Malaria Research Centre, Agogo Presbyterian Hospital
Study officials:
References:
citation: Zaman K, Schuind AE, Adjei S, Antony K, Aponte JJ, Buabeng PB, Qadri F, Kemp TJ, Hossain L, Pinto LA, Sukraw K, Bhat N, Agbenyega T. Safety and immunogenicity of Innovax bivalent human papillomavirus vaccine in girls 9-14 years of age: Interim analysis from a phase 3 clinical trial. Vaccine. 2024 Apr 2;42(9):2290-2298. doi: 10.1016/j.vaccine.2024.02.077. Epub 2024 Mar 1.