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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cervical Cancer

Intervention / Treatment
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* Biological: Cecolin®
* Biological: Gardasil®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 9 Years
Maximum Age: 14 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cecolin® at 0 and 6 months<br>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®<br>* Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine<br>|
| Experimental: Cecolin® at 0 and 12 months<br>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®<br>* Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine<br>|
| Experimental: Cecolin® at 0 and 24 months<br>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®<br>* Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine<br>|
| Active Comparator: Gardasil® at 0 and 6 months<br>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®<br>* Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine<br>|
| Other: Gardasil® at 0 and Cecolin® at 24 months<br>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®<br>* Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine<br>Biological: Gardasil®<br>* Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | One month after the second dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | Baseline, prior to second dose, one month post second dose and 24 months post first dose | 
| 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 | One month after second 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 | One month after second dose | 
| 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 | 24 months after the first dose | 
| 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 | 7 days post vaccination | 
| 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 | One month after each dose | 
| 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 | Throughout the study period |