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Immunogenicity From 1 Dose of Bivalent HPV Vaccine in Girls to 3 Doses of Quadrivalent Vaccine in Women: the PRIMAVERA-ESCUDDO Trial

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ClinicalTrials.gov Identifier: NCT03728881
Recruitment Status : Not yet recruiting
First Posted : November 2, 2018
Last Update Posted : December 17, 2018
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

Background:

Cervical cancer is a dangerous disease caused by a germ called human papillomavirus (HPV). There are 3 safe vaccines that protect women against HPV and cancer. Currently, girls receive 2 doses of HPV vaccine. Researchers want to test if only 1 dose is enough. This study in Costa Rica is one of several new 1-dose studies being done around the world.

Objective:

To find out if giving only 1 dose of the HPV vaccine Cervarix to young girls works the same as giving 3 doses of the HPV vaccine Gardasil to young women.

Eligibility:

Healthy girls ages 9-14

Healthy women ages 18-25

Design:

Participants will be screened with blood and urine tests and questions about their health. Their parents may answer some of the questions.

Participants will get the vaccine as an injection in the arm. They will be observed for 15 minutes each time they get the vaccine.

Participants ages 9-14 will get the Cervarix vaccine 1 time. Six months later, participants (or their parents) will be asked about their health. This contact will be a phone call and will take about 5 minutes.

Participants ages 18-25 will get the Gardasil vaccine 3 times over 6 months.

All participants will have 1 half-hour visit every year for 3 years after getting the vaccine. This can be at the clinic or the participant s home. Participants and/or their parents will answer questions about the participant s health and any vaccines they received since the last contact.

Participants will give a blood sample.


Condition or disease Intervention/treatment Phase
Anti-HPV Antibody Levels Cervical Cancer Biological: Cervarix Biological: Gardasil Phase 3

Detailed Description:

Human papillomavirus (HPV) vaccination successfully prevents targeted HPV infections, related precancerous lesions, and, ultimately, cervical and other HPV-related cancers. Despite the established efficacy of the HPV vaccine, most girls living in areas with the greatest risk for cervical cancer are not being vaccinated. The cost and logistical difficulties of vaccinating girls with the recommended multiple-dose administration has been a significant impediment to preventing this often-fatal cancer.

The goal of this research is to provide convincing and actionable evidence for regulatory bodies that a single dose of the HPV vaccine will elicit an immune response sufficient to protect against targeted HPV infections and subsequent neoplasms. This study will provide earlier and complementary results to the definitive 24,000-girl study evaluating the vaccine efficacy for a 1-dose regimen against virologic outcomes, which is underway in Costa Rica and is scheduled to be completed in 2024/5. That study, called ESCUDDO, is being conducted by the U.S. National Cancer Institute (NCI) and the Agencia Costarricense de Investigaciones Biomedicas (ACIB).

Our specific objective is to show that the immune response for 1-dose of the bivalent vaccine Cervarix in girls 9-14 years old is non-inferior to the immune response for 3-doses of the quadrivalent vaccine Gardasil in women 18-25, a dosage/population combination with demonstrated efficacy. We emphasize that we are evaluating a single dose using the more immunogenic vaccine (i.e. Cervarix) in the population (i.e. 9-14-year-old girls) that has the stronger immune response. Therefore, despite a 1-dose regimen eliciting lower titers than a 3- dose regimen when using the same vaccine and population, we hypothesize that 1-dose of Cervarix in girls will be non-inferior to 3-doses of Gardasil in women. We would expect that a successful demonstration of non-inferiority will provide a direct regulatory pathway for label change, which would in turn promote early adoption of and preparation for 1-dose vaccine programs by relevant agencies (i.e. WHO). We note that new vaccines or new administrations of a vaccine have, in the past, been recommended or approved for licensure by demonstrating that the immune response for the new vaccination plan is non-inferior to the immune response from an existing, approved vaccination plan. For the HPV vaccine, these immunobridging studies have informed the recommendation for a two-dose administration, and vaccination in 9-14 year old girls and boys. Scientifically, this study can provide additional evidence that subunit vaccines with repetitive structures elicit sufficient antibody responses to confer protection and will demonstrate the importance of the adjuvant system to maximize plateau titer levels.

From this effort, we anticipate one of two outcomes, which are summarized below along with their implications.

Outcome #1: The HPV-16 and HPV-18 antibody levels at 24 and/or 36 months from 1-dose of Cervarix in girls 9-14 years old are non-inferior to 3-doses of Gardasil in women 18-25 years old. The implication from this result is that 1-dose of Cervarix will be efficacious for protecting against incident HPV 16/18 infection and associated precancerous lesions. The result could lead to provisional approvals supporting a 1-dose regimen of the bivalent HPV vaccine by international and regulatory agencies (e.g., WHO, FDA, and EMA), contingent on the definitive corroboration of efficacy from ESCUDDO, which will deliver its results three to four years later.

Outcome #2: The HPV-16 and/or HPV-18 antibody levels at 24 and 36 months from 1-dose of Cervarix in girls 9-14 years old cannot be demonstrated to be non-inferior to 3-doses of Gardasil in women 18-25 years old. The implication from this result would be that the vaccine efficacy of a single dose will need to be directly evaluated by demonstration of protection against pertinent virologic outcomes, as planned in our ongoing 1-dose ESCUDDO study.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Non-Inferiority Trial Comparing Immunogenicity From 1-Dose of Bivalent HPV Vaccine in Girls to 3-Doses of Quadrivalent Vaccine in Women: The PRIMAVERA-ESCUDDO Trial ("Puente de Respuesta Inmunologica Para Mejorar el Acceso a Vacunas y ERrAdicar el Cancer")
Estimated Study Start Date : December 20, 2018
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : February 28, 2023

Arm Intervention/treatment
Experimental: Cervarix Group
520 girls ages 9-14 years; Receive 1 dose Cervarix at 0 months
Biological: Cervarix
Vaccine indicated in females 9 through 25 years of age for the prevention of the following diseases: Cervical, vulvar, vaginal, and anal cancer caused by Human Papillomavirus (HPV) types 16 and 18. In Costa Rica, in patients 9-15 years old, this vaccine is approved for two doses (0.5-mL each) intramuscular injection at 0, 6 months (second dose between 5 and 13 months after first dose). Intervention will be one dose at 0 months in 520 girls ages 9-14 years.

Gardasil Group
520 women ages 18-25 years; Receive 3 doses at 0, 2, and 6 months
Biological: Gardasil
Vaccine indicated in females 9 through 26 years of age for the prevention of the following diseases: Cervical, vulvar, vaginal, and anal cancer caused by Human Papillomavirus (HPV) types 16, 18; and Genital warts (condyloma acuminata) caused by HPV types 6 and 11. In Costa Rica, in women 16 years old and older, it is approved for three doses (0.5- mL each) intramuscular injection at 0, 2 months, and 6 months. Intervention will be three doses at 0, 2, and 6 months, in 520 women ages 18-25 years.




Primary Outcome Measures :
  1. The HPV-16 and HPV-18 antibody levels measured at 24 and/or 36 months [ Time Frame: Assessed at 36 months after initial vaccination, withinterim analysis at 24 months ]
    Comparison of immune response for 1-dose of the bivalent vaccine Cervarix in girls 9-14 years old to immune response for 3-doses of the quadrivalent vaccine Gardasil in women 18-25



Information from the National Library of Medicine

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Ages Eligible for Study:   9 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

Potential participants will be deemed eligible if they are:

  • Female;
  • Aged between:

    • 9 and 14 years inclusive for Cervarix group;
    • 18 and 25 years inclusive for Gardasil group;
  • Living in the study area without plans to move outside the country in the next six months;
  • Able to communicate with study personnel;
  • Able and willing to provide a blood sample;
  • Willing to permit export of blood samples to the United States;
  • Willing to participate in the study and:

    • If Cervarix group, sign the informed assent and be supported in study participation by at least one parent (or guardian), who is willing to sign the informed consent document;
    • If Gardasil group, sign the informed consent
  • In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor s criterion).

EXCLUSION CRITERIA:

Potential participants will be excluded from enrollment if:

  • They are diagnosed with chronic conditions, such as autoimmune conditions, degenerative diseases, neurologic or genetic diseases among others;
  • They are allergic to one of the vaccine components, including yeast (if Gardasil) or latex (if Cervarix);
  • They have received immunoglobulins within 90 days preceding enrollment/vaccination visit;
  • They are unwilling to provide a blood sample;
  • Unwilling to permit export of blood samples to the United States;
  • They have a positive urine pregnancy test result;
  • They are pregnant;
  • They are planning to become pregnant.
  • The clinician determining eligibility in agreement with the principal investigator considers that there is a reason that precludes participation;
  • They have been vaccinated against HPV;
  • The participant or her parent/legal guardian, as applicable, does not have an identification document.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03728881


Contacts
Contact: Aimee R. Kreimer, Ph.D. (240) 276-7102 kreimera@mail.nih.gov

Locations
Costa Rica
Agencia Costarricense De Investigaciones Biom(SqrRoot)(Copyright)dicas (ACIB) Not yet recruiting
Liberia, Costa Rica
Contact: Bernal Cortes    50626681128    bcortes@acibcr.com   
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Aimee R. Kreimer, Ph.D. National Cancer Institute (NCI)

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03728881     History of Changes
Other Study ID Numbers: 999919009
19-C-N009
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: December 17, 2018
Last Verified: October 29, 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Fewer Doses
Human Papillomavirus
Cervical Cancer
Costa Rica
HPV-Associated Cancers

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vaccines
Immunologic Factors
Physiological Effects of Drugs