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| Name | Class |
|---|---|
| International Centre for Diarrhoeal Disease Research, Bangladesh | OTHER |
| Malaria Research Centre, Agogo Presbyterian Hospital, Ghana | UNKNOWN |
| Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., USA |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cecolin® at 0 and 6 months | Experimental | 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 |
|
| Cecolin® at 0 and 12 months | Experimental | 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 |
|
| Cecolin® at 0 and 24 months | Experimental | 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 |
|
| Gardasil® at 0 and 6 months | Active Comparator | 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 |
|
| Gardasil® at 0 and Cecolin® at 24 months | Other | 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cecolin® | Biological | Recombinant Human Papillomavirus Bivalent (Types 16, 18) Vaccine |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5). |
| 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. | One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5). |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| GMC of Anti-HPV-16 IgG Antibodies Prior to the Second Dose | 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. | Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5). |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| International Centre for Diarrhoeal Disease Research | Dhaka | Bangladesh | ||||
| Malaria Research Centre, Agogo Presbyterian Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38431444 | Result | 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. | |
| 41276263 |
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Participants were randomized approximately equally within site into one of five treatment groups.
The study was conducted in one clinical site in Bangladesh and one clinical site in Ghana.
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| ID | Title | Description |
|---|---|---|
| FG000 | 1. Cecolin at Month 0 and 6 | Participants received two doses of Cecolin 6 months apart (at Month 0 and Month 6). |
| FG001 | 2. Cecolin at Month 0 and 12 | Participants received two doses of Cecolin 12 months apart (at Month 0 and Month 12). |
| FG002 | 3. Cecolin at Month 0 and 24 | Participants received two doses of Cecolin 24 months apart (at Month 0 and Month 24). |
| FG003 | 4. Gardasil at Month 0 and 6 | Participants received two doses of Gardasil 6 months apart (at Month 0 and Month 6) |
| FG004 | 5. Gardasil at Month 0 and Cecolin at Month 24 | Participants received one dose of Gardasil at Month 0 and one dose of Cecolin at Month 24. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 1. Cecolin at Month 0 and 6 | Participants received two doses of Cecolin 6 months apart (at Month 0 and Month 6). |
| BG001 | 2. Cecolin at Month 0 and 12 | Participants received two doses of Cecolin 12 months apart (at Month 0 and Month 12). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-16 antibody negative at baseline, and had a valid serology result one month after second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | One month after the second dose (Month 7 for Groups 1 & 4, Month 13 for Group 2, and Month 25 for Groups 3 & 5). |
|
Adverse events were collected 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 1. Cecolin at Month 0 and 6 | Participants received two doses of Cecolin 6 months apart (at Month 0 and Month 6). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Inguinal hernia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Niranjan Bhat, MD | PATH | 206 302 4843 | nbhat@path.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 3, 2023 | Dec 11, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 3, 2023 | Dec 11, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| D000068857 | Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18 |
| ID | Term |
|---|---|
| D017778 | Vaccines, Combined |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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| The Emmes Company, LLC | INDUSTRY |
| Xiamen Innovax Biotech Co., Ltd | INDUSTRY |
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| Gardasil® | Biological | Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine |
|
| 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 |
| 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. | 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 |
| 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. | 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 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. | 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). |
| 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). | One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5). |
| 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). | One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5). |
| 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. | 18 months after the second dose (Month 24) |
| 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. | 18 months after the second dose (Month 24) |
| 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:
| For 30 minutes after each vaccination and for up to 7 days after each vaccination |
| 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. | 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) |
| Number of Participants With Serious Adverse Events (SAEs) | An SAE was any AE that resulted in any of the following outcomes:
SAEs were collected from the time of first vaccination through the end of the study for each participant. | 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) |
| GMC of Anti-HPV-18 IgG Antibodies Prior to the Second Dose | 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. | Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5). |
| Agogo |
| Ghana |
| Derived |
| 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. |
| 40120597 | Derived | 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. |
| Lost to Follow-up |
|
| Withdrawal by Subject |
|
| BG002 | 3. Cecolin at Month 0 and 24 | Participants received two doses of Cecolin 24 months apart (at Month 0 and Month 24). |
| BG003 | 4. Gardasil at Month 0 and 6 | Participants received two doses of Gardasil 6 months apart (at Month 0 and Month 6) |
| BG004 | 5. Gardasil at Month 0 and Cecolin at Month 24 | Participants received one dose of Gardasil at Month 0 and one dose of Cecolin at Month 24. |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Participants received two doses of Cecolin 6 months apart (at Month 0 and Month 6). |
| OG001 | 2. Cecolin at Month 0 and 12 | Participants received two doses of Cecolin 12 months apart (at Month 0 and Month 12). |
| OG002 | 3. Cecolin at Month 0 and 24 | Participants received two doses of Cecolin 24 months apart (at Month 0 and Month 24). |
| OG003 | 4. Gardasil at Month 0 and 6 | Participants received two doses of Gardasil 6 months apart (at Month 0 and Month 6) |
| OG004 | 5. Gardasil at Month 0 and Cecolin at Month 24 | Participants received one dose of Gardasil at Month 0 and one dose of Cecolin at Month 24. |
|
|
|
| Primary | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-18 antibody negative at baseline, and had a valid serology result one month after second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | 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 | 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. | Per Protocol Population, PBNA Subset | Posted | Geometric Mean | 95% Confidence Interval | titer | 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 |
|
|
|
| Secondary | 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. | Per Protocol Population, PBNA Subset | Posted | Geometric Mean | 95% Confidence Interval | titer | 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 |
|
|
|
| Secondary | 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. | Per Protocol Population | Posted | Number | percentage of participants | 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). |
|
|
|
| Secondary | 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. | Per Protocol Population | Posted | Number | percentage of participants | 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). |
|
|
|
| Secondary | 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). | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-16 antibody negative at baseline, and had a valid serology result one month after second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5). |
|
|
|
|
| Secondary | 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). | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-16 antibody negative at baseline, and had a valid serology result one month after second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | One month after the second dose (Month 7 for Group 4 and Month 25 for Group 5). |
|
|
|
|
| Secondary | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-16 antibody negative at baseline, and had a valid serology result 18-months after the second dose. Only participants who received the 6 month dose regimens were assessed for this endpoint. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | 18 months after the second dose (Month 24) |
|
|
|
|
| Secondary | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-18 antibody negative at baseline, and had a valid serology result 18 months after the second dose. Only participants who received the 6-month dosing regimens were assessed for this endpoint. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | 18 months after the second dose (Month 24) |
|
|
|
|
| Secondary | 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:
| Total Vaccinated Population includes all randomized participants who received at least one dose of study vaccination. | Posted | Count of Participants | Participants | For 30 minutes after each vaccination and for up to 7 days after each vaccination |
|
|
|
| Secondary | 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. | Total Vaccinated Population includes all randomized participants who received at least one dose of study vaccination. | Posted | Count of Participants | Participants | 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) |
|
|
|
| Secondary | Number of Participants With Serious Adverse Events (SAEs) | An SAE was any AE that resulted in any of the following outcomes:
SAEs were collected from the time of first vaccination through the end of the study for each participant. | Total Vaccinated Population includes all randomized participants who received at least one dose of study vaccination. | Posted | Count of Participants | Participants | 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) |
|
|
|
| Other Pre-specified | GMC of Anti-HPV-16 IgG Antibodies Prior to the Second Dose | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-16 antibody negative at baseline, and had a valid serology result prior to receiving the second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5). |
|
|
|
| Other Pre-specified | GMC of Anti-HPV-18 IgG Antibodies Prior to the Second Dose | 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. | The Per Protocol Population includes participants who had no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccine, were HPV-18 antibody negative at baseline, and had a valid serology result prior to receiving the second dose. | Posted | Geometric Mean | 95% Confidence Interval | IU/mL | Prior to the second dose (Month 6 for Groups 1 & 4, Month 12 for Group 2, and Month 24 for Groups 3 & 5). |
|
|
|
| 0 |
| 205 |
| 4 |
| 205 |
| 155 |
| 205 |
| EG001 | 2. Cecolin at Month 0 and 12 | Participants received two doses of Cecolin 12 months apart (at Month 0 and Month 12). | 0 | 206 | 0 | 206 | 145 | 206 |
| EG002 | 3. Cecolin at Month 0 and 24 | Participants received two doses of Cecolin 24 months apart (at Month 0 and Month 24). | 0 | 204 | 5 | 204 | 130 | 204 |
| EG003 | 4. Gardasil at Month 0 and 6 | Participants received two doses of Gardasil 6 months apart (at Month 0 and Month 6) | 0 | 205 | 4 | 205 | 165 | 205 |
| EG004 | 5. Gardasil at Month 0 and Cecolin at Month 24 | Participants received one dose of Gardasil at Month 0 and one dose of Cecolin at Month 24. | 1 | 205 | 3 | 205 | 145 | 205 |
| Umbilical hernia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Abscess | Infections and infestations | MedDRA | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Bacterial sepsis | Infections and infestations | MedDRA | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA | Systematic Assessment |
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| Plasmodium falciparum infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Typhoid fever | Infections and infestations | MedDRA | Systematic Assessment |
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| Animal bite | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Skin laceration | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Snake bite | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
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| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA | Systematic Assessment |
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| Premature rupture of membranes | Pregnancy, puerperium and perinatal conditions | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vaccination site pain | General disorders | MedDRA | Systematic Assessment |
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| Fatigue | General disorders | MedDRA | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA | Systematic Assessment |
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| Chills | General disorders | MedDRA | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Malaria | Infections and infestations | MedDRA | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
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The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review.
| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D053918 |
| Papillomavirus Vaccines |
| D014765 | Viral Vaccines |
Non-inferiority was to be demonstrated if the lower bound of the 98.3% confidence interval of the geometric mean concentration (GMC) ratio was greater than the non-inferiority margin of 0.5 for both HPV-16 and HPV-18. |
| The primary objective included three non-inferiority comparisons of Cecolin at 0 and 6 months, 0 and 12 months, or 0 and 24 months compared to Gardasil at 0 and 6 months. To control the type I error for the three co-primary non-inferiority hypotheses, a Bonferroni correction corresponding to 98.3% confidence intervals (CI) was used. | GMC Ratio | 1.68 | 2-Sided | 98.3 | 1.372 | 2.069 | GMC ratios (Cecolin/Gardasil) and corresponding confidence limits were calculated using linear models of the log concentration values adjusted by site and transformed back to the original scale. | Non-Inferiority | Non-inferiority was to be demonstrated if the lower bound of the 98.3% confidence interval of the geometric mean concentration (GMC) ratio was greater than the non-inferiority margin of 0.5 for both HPV-16 and HPV-18. |
| The primary objective included three non-inferiority comparisons of Cecolin at 0 and 6 months, 0 and 12 months, or 0 and 24 months compared to Gardasil at 0 and 6 months. To control the type I error for the three co-primary non-inferiority hypotheses, a Bonferroni correction corresponding to 98.3% confidence intervals (CI) was used. | GMC Ratio | 1.71 | 2-Sided | 98.3 | 1.389 | 2.102 | GMC ratios (Cecolin/Gardasil) and corresponding confidence limits were calculated using linear models of the log concentration values adjusted by site and transformed back to the original scale. | Non-Inferiority | Non-inferiority was to be demonstrated if the lower bound of the 98.3% confidence interval of the geometric mean concentration (GMC) ratio was greater than the non-inferiority margin of 0.5 for both HPV-16 and HPV-18. |
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| One Month after Second Dose |
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| 18-Months after Second Dose |
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| One Month after Second Dose |
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| 18-Months after Second Dose |
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| Within 30 Minutes of Vaccination: Any Systemic Reactions |
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| Within 7 Days of Vaccination: Any Local Reactions |
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| Within 7 Days of Vaccination: Any Systemic Reactions |
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