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

Primary Purpose

Cervical Cancer

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Cecolin®

Gardasil®

About this trial

This is an interventional prevention trial for Cervical Cancer

Eligibility Criteria

9 Years - 14 Years (Child)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

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/LAR 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

Exclusion Criteria:

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 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

Sites / Locations

International Centre for Diarrhoeal Disease Research
Malaria Research Centre, Agogo Presbyterian Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Other

Arm Label

Cecolin® at 0 and 6 months

Cecolin® at 0 and 12 months

Cecolin® at 0 and 24 months

Gardasil® at 0 and 6 months

Gardasil® at 0 and Cecolin® at 24 months

Arm Description

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

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

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

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

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.

Outcomes

Primary Outcome Measures

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

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

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

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)

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))

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

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

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

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

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

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

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

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

Number of subjects in each study arm reporting unsolicited adverse events

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

Number of subjects in each study arm reporting serious adverse events

Full Information

NCT ID

NCT04508309

First Posted

August 4, 2020

Last Updated

April 26, 2022

Sponsor

PATH

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04508309

Brief Title

Phase 3 Trial of a Bivalent 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

2. Study Status

Record Verification Date

February 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 15, 2021 (Actual)

Primary Completion Date

January 15, 2024 (Anticipated)

Study Completion Date

January 15, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

PATH

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cervical Cancer

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1025 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cecolin® at 0 and 6 months

Arm Type

Experimental

Arm Description

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

Arm Title

Cecolin® at 0 and 12 months

Arm Type

Experimental

Arm Description

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

Arm Title

Cecolin® at 0 and 24 months

Arm Type

Experimental

Arm Description

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

Arm Title

Gardasil® at 0 and 6 months

Arm Type

Active Comparator

Arm Description

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

Arm Title

Gardasil® at 0 and Cecolin® at 24 months

Arm Type

Other

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Cecolin®

Intervention Description

Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine

Intervention Type

Biological

Intervention Name(s)

Gardasil®

Intervention Description

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

Primary Outcome Measure Information:

Title

Description

Time Frame

One month after the second dose

Secondary Outcome Measure Information:

Title

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

Description

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)

Time Frame

Baseline, prior to second dose, one month post second dose and 24 months post first dose

Title

Description

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

Time Frame

One month after second dose

Title

Description

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

Time Frame

One month after second dose

Title

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

Description

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

Time Frame

24 months after the first dose

Title

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

Description

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

Time Frame

7 days post vaccination

Title

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

Description

Number of subjects in each study arm reporting unsolicited adverse events

Time Frame

One month after each dose

Title

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

Description

Number of subjects in each study arm reporting serious adverse events

Time Frame

Throughout the study period

Other Pre-specified Outcome Measures:

Title

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

Description

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)

Time Frame

Baseline, prior to second dose, one month post second dose

Title

Evaluate the persistence of antibody responses following a single dose of either Gardasil® or Cecolin® at 6, 12, and 24 months

Description

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

Time Frame

6 months after first dose, 12 months after first dose, 24 months after first dose

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

9 Years

Maximum Age & Unit of Time

14 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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/LAR 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 Exclusion Criteria: 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 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

Facility Information:

Facility Name

International Centre for Diarrhoeal Disease Research

City

Dhaka

Country

Bangladesh

Facility Name

Malaria Research Centre, Agogo Presbyterian Hospital

City

Agogo

Country

Ghana

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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