Phase 3 Trial of a Bivalent Human Papilloma Virus (HPV) Vaccine (Cecolin®) in Young Girls

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

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.

Study Overview

• Status: Completed
• Conditions: Cervical Cancer
• Intervention / Treatment: Biological: Cecolin®; Biological: Gardasil®

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.

• Study Type: Interventional
• Enrollment (Actual): 1025
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • International Centre for Diarrhoeal Disease Research
• Ghana
  • Agogo, Ghana
    • Malaria Research Centre, Agogo Presbyterian Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 14 years (Child)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cecolin® at 0 and 6 months; Two doses of Cecolin® given at 0 and 6 months with blood draw at baseline, prior to second dose, one-month post second dose and 24 months after first dose	Biological: Cecolin®; Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine
Experimental: Cecolin® at 0 and 12 months; Two doses of Cecolin® given at 0 and 12 months with blood draw at baseline, prior to second dose and one-month post second dose	Biological: Cecolin®; Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine
Experimental: Cecolin® at 0 and 24 months; Two doses of Cecolin® given at 0 and 24 months with blood draw at baseline, prior to second dose and one-month post second dose	Biological: Cecolin®; Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine
Active Comparator: Gardasil® at 0 and 6 months; Two doses of Gardasil® given at 0 and 6 months with blood draw at baseline, prior to second dose, one-month post second dose and 24 months after first dose	Biological: Gardasil®; Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine
Other: Gardasil® at 0 and Cecolin® at 24 months; One dose of Gardasil® at 0 months and one dose of Cecolin® at 24 months with blood draw at baseline, prior to second dose and one-month post second dose.	Biological: Cecolin®; Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine; Biological: Gardasil®; Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Concentration (GMC) of Anti-HPV-16 Immunoglobulin G (IgG) Antibodies One Month After the Second Dose	Anti-HPV-16 IgG antibodies were measured using HPV-16 virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA) one month after the second dose at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-16 assay was 1.41 international units (IU)/mL.	One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).
Geometric Mean Concentration of Anti-HPV-18 Immunoglobulin G Antibodies One Month After the Second Dose	Anti-HPV-18 IgG antibodies were measured using HPV-18 VLP ELISA one month after the second dose at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-18 assay was 1.05 IU/mL.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titer (GMT) of Anti-HPV-16 Neutralizing Antibodies	Anti-HPV 16 serum neutralizing antibodies were measured in a subset of participants by pseudovirion-based neutralization assay (PBNA) at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-16 PBNA was a titer of < 21. Samples were collected prior to the second dose and 1 month after the second dose for all treatment groups, and 18 months after the second dose for participants in Groups 1 and 4.	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
Geometric Mean Titer (GMT) of Anti-HPV-18 Neutralizing Antibodies	Anti-HPV 18 serum neutralizing antibodies were measured in a subset of participants by pseudovirion-based neutralization assay (PBNA) at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-18 PBNA was a titer of < 16. Samples were collected prior to the second dose and 1 month after the second dose for all treatment groups, and 18 months after the second dose for participants in Groups 1 and 4.	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
Seroconversion Rate For HPV-16 One Month After the Second Dose	Seroconversion rate is defined as the percentage of participants with a 4-fold rise in anti-HPV 16 IgG antibodies as measured by ELISA from baseline one month following the second dose.	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).
Seroconversion Rate For HPV-18 One Month After the Second Dose	Seroconversion rate is defined as the percentage of participants with a 4-fold rise from baseline in anti HPV-18 IgG antibodies as measured by ELISA one month following the second dose.	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).
GMC of Anti-HPV-16 IgG Antibodies One Month After the Second Dose: Comparison of Gardasil/Cecolin Mixed Dose With Gardasil 2-dose Regimen	Anti-HPV-16 IgG antibodies were measured using HPV-16 VLP ELISA one month after the second dose at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-16 assay was 1.41 IU/mL. Anti-HPV-16 IgG GMCs measured 1 month after the second dose were compared between the Gardasil at Month 0 and Cecolin at 24 months two-dose regimen (Group 5) and the Gardasil at Month 0 and 6 two-dose regimen (Group 4).	One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5).
GMC of Anti-HPV-18 IgG Antibodies One Month After the Second Dose: Comparison of Gardasil/Cecolin Mixed Dose With Gardasil 2-dose Regimen	Anti-HPV-18 IgG antibodies were measured using HPV-18 VLP ELISA one month after the second dose at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, United States. The lower limit of quantitation of the HPV-18 assay was 1.405 IU/mL. Anti-HPV-18 IgG GMCs measured 1 month after the second dose were compared between the Gardasil at Month 0 and Cecolin at 24 Months two-dose regimen (Group 5) and the Gardasil at Month 0 and 6 two-dose regimen (Group 4).	One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5).
GMC of Anti-HPV-16 IgG Antibodies 18-Months After Second Dose	Anti-HPV-16 IgG antibodies were measured using HPV-16 VLP ELISA 18 months after the second dose for participants who received a 6-month dosing regimen (Groups 1 and 4) only.	18 months after the second dose (Month 24)
GMC of Anti-HPV-18 IgG Antibodies 18-Months After Second Dose	Anti-HPV-18 IgG antibodies were measured using HPV-18 VLP ELISA 18 months after the second dose for participants who received a 6-month dosing regimen (Groups 1 and 4) only.	18 months after the second dose (Month 24)
Number of Participants With Solicited Adverse Events	Solicited adverse events (AEs) were assessed by study staff 30 minutes after each vaccination and then daily for seven days after each vaccination by the participants using a memory aid. The following specific solicited AEs were monitored for this trial: Local Reactions:Pain, erythema/redness, swelling, induration, pruritus, abscess.; General/Systemic Reactions:Fever (oral or axillary temperature ≥ 38.0°C), headache, vomiting, nausea, fatigue, chills, muscle pain, cough, diarrhea, dizziness, allergic dermatitis, rash, syncope, and anorexia.	For 30 minutes after each vaccination and for up to 7 days after each vaccination
Number of Participants With Unsolicited Adverse Events	Unsolicited AEs were any AEs reported spontaneously by the participant, identified during interview at study visits, observed by the study personnel during study visits or those identified during review of medical records or source documents. Unsolicited AEs were events occurring from the time of each study injection through approximately 30 days after each vaccination. Solicited AEs with onset after the solicitation period and through Day 30 post-vaccination were captured as unsolicited AEs.	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)
Number of Participants With Serious Adverse Events (SAEs)	An SAE was any AE that resulted in any of the following outcomes: Death; Was life-threatening; Required inpatient hospitalization or prolongation of existing hospitalization.; Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions.; Congenital abnormality or birth defect.; Important medical event that may not have resulted in one of the above outcomes but may have jeopardized the health of the study participant or (and) required medical or surgical intervention to prevent one of the outcomes listed in the above definition of SAEs. SAEs were collected from the time of first vaccination through the end of the study for each participant.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMC of Anti-HPV-16 IgG Antibodies Prior to the Second Dose	To evaluate the persistence of antibody responses to HPV after a single dose of vaccine, anti-HPV-16 IgG antibodies were measured using HPV-16 VLP ELISA immediately prior to the second dose.	Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5).
GMC of Anti-HPV-18 IgG Antibodies Prior to the Second Dose	To evaluate the persistence of antibody responses to HPV after a single dose of vaccine, anti-HPV-18 IgG antibodies were measured using HPV-16 VLP ELISA immediately prior to the second dose.	Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5).

Collaborators and Investigators

• Sponsor: PATH
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh; The Emmes Company, LLC; Xiamen Innovax Biotech Co., Ltd; Malaria Research Centre, Agogo Presbyterian Hospital, Ghana; Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., USA

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2021
• Primary Completion (Actual): December 14, 2023
• Study Completion (Actual): December 14, 2023

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (Actual): August 11, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms
• Other Study ID Numbers: CVIA-087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No