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Completed

NCT Number: NCT04508309

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

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.

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Key information

Conditions

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

Age range

9 year–14 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 3

Primary location

International Centre for Diarrhoeal Disease Research, Dhaka, Bangladesh

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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/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

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 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

Treatment and study plan

Cecolin®

Biological

Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine

GARDASIL®

Biological

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

Primary outcomes

  1. Geometric Mean Concentration (GMC) of Anti-HPV-16 Immunoglobulin G (IgG) Antibodies One Month After the Second Dose

    Time frame: One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).

    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.

  2. Geometric Mean Concentration of Anti-HPV-18 Immunoglobulin G Antibodies One Month After the Second Dose

    Time frame: One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5).

    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.

Secondary outcomes

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

    Time frame: 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

    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.

  2. Geometric Mean Titer (GMT) of Anti-HPV-18 Neutralizing Antibodies

    Time frame: 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

    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.

  3. Seroconversion Rate For HPV-16 One Month After the Second Dose

    Time frame: 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 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.

  4. Seroconversion Rate For HPV-18 One Month After the Second Dose

    Time frame: 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 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.

  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

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

    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).

  6. GMC of Anti-HPV-18 IgG Antibodies One Month After the Second Dose: Comparison of Gardasil/Cecolin Mixed Dose With Gardasil 2-dose Regimen

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

    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).

  7. GMC of Anti-HPV-16 IgG Antibodies 18-Months After Second Dose

    Time frame: 18 months after the second dose (Month 24)

    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.

  8. GMC of Anti-HPV-18 IgG Antibodies 18-Months After Second Dose

    Time frame: 18 months after the second dose (Month 24)

    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.

  9. Number of Participants With Solicited Adverse Events

    Time frame: For 30 minutes after each vaccination and for up to 7 days after each vaccination

    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.

  10. Number of Participants With Unsolicited Adverse Events

    Time frame: 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)

    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.

  11. Number of Participants With Serious Adverse Events (SAEs)

    Time frame: 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)

    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.

Other outcomes

  1. GMC of Anti-HPV-16 IgG Antibodies Prior to the Second Dose

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

    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.

  2. GMC of Anti-HPV-18 IgG Antibodies Prior to the Second Dose

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

    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.

Sponsors and collaborators

Lead sponsor

PATH

Other

Collaborators

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

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Aug 11, 2020
Registry last updated
Jan 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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