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

Sponsor
PATH (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT04508309
Collaborator
International Centre for Diarrhoeal Disease Research, Bangladesh (Other), Malaria Research Centre, Agogo Presbyterian Hospital, Ghana (Other), Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., USA (Other), The Emmes Company, LLC (Industry), Xiamen Innovax Biotech Co., Ltd (Industry)
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Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Cecolin®
  • Biological: Gardasil®
Phase 3

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). 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1025 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Prevention
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
Actual Study Start Date :
Mar 15, 2021
Anticipated Primary Completion Date :
Jan 15, 2024
Anticipated Study Completion Date :
Jan 15, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Demonstrate the non-inferiority of Cecolin® administered on 0, 6-month; 0, 12-month; and 0, 24-month 2-dose regimens, to Gardasil® using a 0, 6-month 2-dose regimen, based on HPV IgG levels measured one month post last dose for HPV types 16 and 18 [One month after the second dose]

    Anti-HPV 16 and 18 IgG antibody geometric mean concentration (GMC), measured by enzyme-linked immunosorbent assay (ELISA) one month after the second dose for the 0, 6-month arms, for the 0, 12-month arm or for the 0, 24-month arm following vaccination

Secondary Outcome Measures

  1. Evaluate immunogenicity of Cecolin® and Gardasil®, in all study arms, based on a functional assay pseudovirion-based neutralization assay (PBNA) to measure antibody levels at all time points [Baseline, prior to second dose, one month post second dose and 24 months post first dose]

    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)

  2. Describe seroconversion rates one month after the last dose of Cecolin® (All schedules: 0, 6-month; 0, 12-month; 0, 24-month; and mixed 0, 24-month) and after the last dose of Gardasil® (0, 6-month schedule)) [One month after second dose]

    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

  3. Evaluate the non-inferiority of a mixed 2-dose regimen consisting of a single dose of Gardasil® followed by a single dose of Cecolin® given 24 months later (0, 24-month schedule), to Gardasil® using a 0, 6-month two dose regimen for HPV types 16 and 18 [One month after second dose]

    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

  4. Evaluate the non-inferiority of Cecolin® administered on 0-6 months to Gardasil® given on a 0-6 month schedule at 24 months post-first dose [24 months after the first dose]

    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

  5. Evaluate the safety of Cecolin® in 9-14-year-old females across multiple geographies administered in two-dose regimens in terms of solicited local and systemic adverse events [7 days post vaccination]

    Number of subjects in each study arm reporting solicited local and systemic adverse events

  6. Evaluate the safety of Cecolin® in 9-14-year-old females across multiple geographies administered in two-dose regimens in terms of unsolicited adverse events [One month after each dose]

    Number of subjects in each study arm reporting unsolicited adverse events

  7. Evaluate the safety of Cecolin® in 9-14-year-old females across multiple geographies administered in two-dose regimens in terms of Serious Adverse Events [Throughout the study period]

    Number of subjects in each study arm reporting serious adverse events

Other Outcome Measures

  1. Conduct anti-HPV antibody kinetic modeling based on measurements at baseline, at the time of second dose, and one month after the second dose to determine dose response curves and optimized windows for length of the dose interval [Baseline, prior to second dose, one month post second dose]

    HPV IgG GMC by ELISA and GMT by PBNA at baseline, at the time of second dose, and one month after the second dose (for immunologic bridging and kinetic modeling)

  2. Evaluate the persistence of antibody responses following a single dose of either Gardasil® or Cecolin® at 6, 12, and 24 months [6 months after first dose, 12 months after first dose, 24 months after first dose]

    HPV IgG GMC by ELISA following a single dose of Gardasil® or Cecolin® at 6, 12, and 24 months

Eligibility Criteria

Criteria

Ages Eligible for Study:
9 Years to 14 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
Yes
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/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

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 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

Contacts and Locations

Locations

Site City State Country Postal Code
1 International Centre for Diarrhoeal Disease Research Dhaka Bangladesh
2 Malaria Research Centre, Agogo Presbyterian Hospital Agogo Ghana

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
PATH
ClinicalTrials.gov Identifier:
NCT04508309
Other Study ID Numbers:
  • CVIA-087
First Posted:
Aug 11, 2020
Last Update Posted:
Apr 27, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 27, 2022