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

NCT04508309 | Completed Phase 3 Results DMC

• 1 other identifier: CVIA-087
• Study Type: interventional
• Target: 1,025
• Locations: 2 countries
• Sites: 2

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.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (11)

• Geometric Mean Titer (GMT) of Anti-HPV-16 Neutralizing Antibodies

  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

  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

  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

  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

  One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5).

Other Outcomes (2)

• GMC of Anti-HPV-16 IgG Antibodies 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

  Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5).

Study Arms (5)

Cecolin® at 0 and 6 months

EXPERIMENTAL

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®

Cecolin® at 0 and 12 months

EXPERIMENTAL

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®

Cecolin® at 0 and 24 months

EXPERIMENTAL

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®

Gardasil® at 0 and 6 months

ACTIVE COMPARATOR

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®

Gardasil® at 0 and Cecolin® at 24 months

OTHER

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®; Biological: Gardasil®

Interventions

Cecolin® BIOLOGICAL

Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine

Cecolin® at 0 and 12 months; Cecolin® at 0 and 24 months; Cecolin® at 0 and 6 months; Gardasil® at 0 and Cecolin® at 24 months

Gardasil® BIOLOGICAL

Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine

Gardasil® at 0 and 6 months; Gardasil® at 0 and Cecolin® at 24 months

Eligibility Criteria

• Age: 9 Years - 14 Years
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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
• Ability and willingness to provide parental consent and, if applicable based on local in-country regulations, participant assent
• Parent/Legally Acceptable Representative provides informed consent
• Anticipated ability and willingness to complete all study visits and evaluations
• Living within the catchment area of the study without plans to move during the conduct of the study

You may not qualify if:

• Presence of fever or acute disease on the day of vaccination (oral or axillary temperature ≥ 38˚ C)
• If participants have childbearing potential, must not be breastfeeding or confirmed pregnant
• Receipt of an investigational product within 30 days prior to randomization
• Receipt of blood and/or blood products (including immunoglobulin) 3 months prior to any dose of vaccination or blood sampling
• 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
• History of any physical, mental, or developmental disorder that may hinder a participant's ability to comply with the study requirements
• Any malignancy or confirmed or suspected immunodeficient condition such as HIV infection, based on medical history and physical examination
• Receipt of or history of receipt of any medications or treatments that affect the immune system
• Allergies to any components of the vaccine
• Current or former participation in HPV vaccine related research.
• Prior receipt of an investigational or licensed HPV vaccine
• 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

Sponsors & Collaborators

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

Study Sites (2)

International Centre for Diarrhoeal Disease Research

Dhaka, Bangladesh

Location

Malaria Research Centre, Agogo Presbyterian Hospital

Agogo, Ghana

Location

Related Publications (3)

• 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.

  PMID: 38431444 RESULT

• Bergman H, Henschke N, Arevalo-Rodriguez I, Buckley BS, Crosbie EJ, Davies JC, Dwan K, Golder SP, Loke YK, Probyn K, Petkovic J, Villanueva G, Morrison J. Human papillomavirus (HPV) vaccination for the prevention of cervical cancer and other HPV-related diseases: a network meta-analysis. Cochrane Database Syst Rev. 2025 Nov 24;11(11):CD015364. doi: 10.1002/14651858.CD015364.pub2.

  PMID: 41276263 DERIVED

• Agbenyega T, Schuind AE, Adjei S, Antony K, Aponte JJ, Buabeng PBY, Clemens JD, Hossain L, Kemp TJ, Mercer LD, Pinto LA, Qadri F, Sukraw K, Bhat N, Zaman K. Immunogenicity and safety of an Escherichia coli-produced bivalent human papillomavirus vaccine (Cecolin) in girls aged 9-14 years in Ghana and Bangladesh: a randomised, controlled, open-label, non-inferiority, phase 3 trial. Lancet Infect Dis. 2025 Aug;25(8):861-872. doi: 10.1016/S1473-3099(25)00031-3. Epub 2025 Mar 19.

  PMID: 40120597 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Results Point of Contact

• Title: Niranjan Bhat, MD
• Organization: PATH

nbhat@path.org

206 302 4843

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2020
• First Posted: August 11, 2020
• Study Start: March 15, 2021
• Primary Completion: December 14, 2023
• Study Completion: December 14, 2023
• Last Updated: January 30, 2025
• Results First Posted: January 30, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1); GH (1)