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Cervical CancerPhase 3NCT04508309

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

A Phase 3 study testing Cecolin® and Gardasil® in people with Cervical Cancer, run by PATH at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 9 to 14 years, women onlyHealthy volunteers can take part
Conditions the study is for
Cervical Cancer
What is being tested?
Cecolin® and Gardasil®
Type of treatment
Vaccines
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,025 participants
Where
2 sitesin 2 countries
Study dates
15 Mar 2021to 14 Dec 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 9 to 14 years
  • Women only
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Bangladesh1 site
  • International Centre for Diarrhoeal Disease Research

    Dhaka

Other trials in Bangladesh

Ghana1 site
  • Malaria Research Centre, Agogo Presbyterian Hospital

    Agogo

Other trials in Ghana

About this study

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

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.

Read the 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). 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.

Conditions
Cervical Cancer
Being tested
Cecolin®, Gardasil®
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cecolin®Biological

    Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine

  • Gardasil®Biological

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

Study groups in NCT04508309
Study groupRoleWhat they receive
Cecolin® at 0 and 6 monthsExperimentalTwo 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
Receives: Biological: Cecolin®
Cecolin® at 0 and 12 monthsExperimentalTwo doses of Cecolin® given at 0 and 12 months with blood draw at baseline, prior to second dose and one-month post second dose
Receives: Biological: Cecolin®
Cecolin® at 0 and 24 monthsExperimentalTwo doses of Cecolin® given at 0 and 24 months with blood draw at baseline, prior to second dose and one-month post second dose
Receives: Biological: Cecolin®
Gardasil® at 0 and 6 monthsActive comparatorTwo 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
Receives: Biological: Gardasil®
Gardasil® at 0 and Cecolin® at 24 monthsOtherOne 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.
Receives: Biological: Cecolin®; Biological: Gardasil®

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

    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.

    Measured: 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

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

    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.

    Measured: 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

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

    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.

    Measured: 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).

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

    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.

    Measured: 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).

  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

    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).

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

  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

    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).

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

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

    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.

    Measured: 18 months after the second dose (Month 24)

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

    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.

    Measured: 18 months after the second dose (Month 24)

  9. Number of Participants With Solicited Adverse Events

    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.

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

  10. Number of Participants With Unsolicited Adverse Events

    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.

    Measured: 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)

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

    An SAE was any AE that resulted in any of the following outcomes:

    1. Death
    2. Was life-threatening
    3. Required inpatient hospitalization or prolongation of existing hospitalization.
    4. Resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions.
    5. Congenital abnormality or birth defect.
    6. 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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2020
  2. Study start15 Mar 2021
  3. Primary completion14 Dec 2023
  4. Study completion14 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,025 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04508309
Sponsor's protocol ID
CVIA-087
Status last verified
Dec 2024
First submitted
4 Aug 2020
Last updated
30 Jan 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38431444
  • 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.

    PubMed 41276263
  • 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.

    PubMed 40120597

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cecolin® and Gardasil® in people with Cervical Cancer, run by PATH at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Bangladesh, Ghana. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04508309, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.

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Clinical Trial NCT04508309 | AzTrials