Single Dose of Cervarix Vaccine in Girls or Three Doses of Gardasil Vaccine in Women for the Prevention of Human Papillomavirus Infection, the PRIMAVERA-ESCUDDO Trial

NCT03728881 | Completed Phase 3 Results DMC

• 2 other identifiers: NCI-2020-0743219-C-N009
• Study Type: interventional
• Target: 1,240
• Locations: 1 country
• Sites: 1

Brief Summary

This phase IIIb trial compares a single dose of the Cervarix vaccine in girls to 3 doses of the Gardasil vaccine in young women for the prevention of human papillomavirus (HPV) infection. Cervarix is a vaccine used to prevent cervical cancer caused by HPV types 16 and 18. Gardasil is vaccine used to prevent cervical, vulvar, and vaginal cancer caused by HPV types 16 and 18 and genital warts caused by HPV types 6 and 11. Giving only one dose of the Cervarix vaccine in girls may work the same as 3 doses of the Gardasil vaccine in young women in preventing HPV infection and ultimately, cervical and other HPV-related cancers. Currently, many women around the world cannot get HPV vaccines because they are too expensive. If this trial can show one dose given to young girls is enough to prevent cancer, more girls might be able to get the vaccine.

Conditions

Human Papillomavirus-Related Cervical Carcinoma

Keywords

HPV vaccine; Single dose HPV vaccination

Outcome Measures

Primary Outcomes (8)

• Number Seropositive for HPV16 at 36 Months

  Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA concentration is greater than 1.41 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV16 result will be excluded only from the 36-month HPV16 analysis.

  36 months following initial HPV vaccination

• Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2 and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination

  Will measure HPV-16 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the GMT ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months.

  36 months following initial vaccination

• Number Seropositive for HPV18 at 36 Months

  Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA concentration is greater than 1.05 IU/mL. Participants whose analysis of the 36-month sample does not generate a valid HPV18 result will be excluded only from the 36-month HPV18 analysis.

  36 months following initial vaccination

• Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 36 Months After Initial Vaccination

  Will measure HPV-18 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the GMT ratios for HPV-16 and HPV-18 at 24 months and the two-sided 96% confidence intervals of the GMT ratios for HPV-16 and HPV-18 at 36 months.

  36 months following initial vaccination

• Number Seropositive for HPV16 at 24 Months

  Will measure HPV16 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV16 is seropositive if the ELISA titer is greater than 1.41 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV16 result will be excluded only from the 24-month HPV16 analysis.

  24 months following initial HPV vaccination

• Immunogenicity for HPV16 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination

  Will measure HPV-16 specific serum antibody using the HPV type-specific enzyme-linked immunoassay (ELISA) on serum. Will estimate the two-sided 99% confidence interval of the geometric mean concentration (GMC) ratio for HPV-16 at 24 months

  24 months following initial vaccination

• Number Seropositive for HPV18 at 24 Months

  Will measure HPV18 specific serum antibody using the HPV type-specific ELISA on serum. For computing proportions seropositive and proportions seroconverting, HPV18 is seropositive if the ELISA titer is greater than 1.05 IU/mL. Participants whose analysis of the 24-month sample does not generate a valid HPV18 result will be excluded only from the 24-month HPV18 analysis.

  24 months following initial vaccination

• Immunogenicity for HPV18 of One Dose of Bivalent HPV Vaccine (Cervarix) in 9-14 Year Old Girls Compared to Three Doses of Quadrivalent HPV Vaccine (Gardasil), Administered at 0,2, and 6 Months, in 18-25 Year Old Women, 24 Months After Initial Vaccination

  Will measure HPV-18 specific serum antibody using the HPV type-specific ELISA on serum. Will estimate the two-sided 99% confidence interval of the Geometric Mean Concentration (GMC) ratio for HPV-18 at 24 months.

  24 months following initial vaccination

Secondary Outcomes (68)

• Comparison of Proportions With Seroconversion Based on HPV16 Antibody Levels Assessed at 36 Months

  36 months

• Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 36 Months

  36 month

• Comparison of Proportions With Seroconversion Based HPV16 Antibody Levels at 24 Months

  24 months

• Comparison of Proportions With Seroconversion Based on HPV18 Antibody Levels Assessed at 24 Months

  24 months

• Comparison of Distribution of HPV16 Antibodies Levels Assessed at 36 Months

  36 months following initial vaccination

Study Arms (2)

Girls (1D Cervarix®)

EXPERIMENTAL

Participants 9-14 years old receive Cervarix IM at baseline.

Biological: Recombinant Human Papillomavirus Bivalent Vaccine

Women (3D Gardasil-4®)

ACTIVE COMPARATOR

Participants 18-25 years old receive Gardasil IM at baseline and at 2 and 6 months in the absence of unacceptable toxicity.

Biological: Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine

Interventions

Quadrivalent Human Papillomavirus (types 6, 11, 16, 18) Recombinant Vaccine BIOLOGICAL

Given IM

Also known as: Gardasil, Quadrivalent HPV [Type 6, 11, 16 and 18] L1 Virus-Like Particle vaccine, quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccine, Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine, V501

Women (3D Gardasil-4®)

Recombinant Human Papillomavirus Bivalent Vaccine BIOLOGICAL

Given IM

Also known as: Cervarix, GSK-580299, HPV 16/18 L1 VLP/AS04 VAC, HPV-16/18 VLP/AS04 Vaccine, Human Papillomavirus 16/18 L1 Virus-Like Particle/AS04 Vaccine, Human Papillomavirus Bivalent Types 16 and 18 Vaccine, Recombinant, Human Papillomavirus Vaccine L1 16,18, Human Papillomavirus Vaccine, L1 Type 16, 18, Recombinant HPV Bivalent Vaccine

Girls (1D Cervarix®)

Eligibility Criteria

• Age: 9 Years - 25 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Aged between:
• and 14 years inclusive for Cervarix group
• 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 and less than 12 years old, receive study information and be supported in study participation by at least one of parent (or guardian), who is willing to sign the informed consent document
• If Cervarix group and 12 years old or older, 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)

You may not qualify if:

• They have a diagnosis of an autoimmune, degenerative, or neurological disease without treatment or adequate control; a progressive or severe neurological disease; a genetic immunodeficiency; or any other serious chronic disease without treatment and / or adequate control that, according to the principal investigator or designee, for which vaccination is contraindicated (NOTE: Potential participants with these conditions can be included after consultation with the external medical advisor of the study or with an appropriate specialist)
• They are allergic to one of the vaccine components, including yeast (if Gardasil group)
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Cancer Research UK: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

Agencia Costarricense de Investigaciones Biomédicas (ACIB)

Liberia, Guanacaste Province, 50101, Costa Rica

Location

Related Publications (1)

• Cortes B, Ocampo R, Porras C, Liu D, Gail MH, Sierra MS, Herrero R, Lowy DR, Carvajal LJ, Kemp TJ, Fantin R, Schussler J, Hildesheim A, Sampson JN, Pinto LA, Schiller JT, Kreimer AR. Human papillomavirus (HPV) type 16 and type 18 antibody concentrations after a single dose of bivalent HPV vaccine in girls aged 9-14 years compared with three doses of quadrivalent HPV vaccine in women aged 18-25 years in Costa Rica (PRIMAVERA): a non-randomised, open-label, immunobridging, non-inferiority trial. Lancet Infect Dis. 2025 Dec;25(12):1314-1324. doi: 10.1016/S1473-3099(25)00284-1. Epub 2025 Jul 16.

  PMID: 40683285 BACKGROUND

MeSH Terms

Interventions

Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18; human papillomavirus vaccine, L1 type 16, 18

Intervention Hierarchy (Ancestors)

Vaccines, Combined; Vaccines; Biological Products; Complex Mixtures; Papillomavirus Vaccines; Viral Vaccines

Results Point of Contact

• Title: Aimée R. Kreimer, PhD
• Organization: Division of Cancer Epidemiology and Genetics, NCI

kreimera@mail.nih.gov

240.276.7102

Study Officials

• Aimee R Kreimer

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2018
• First Posted: November 2, 2018
• Study Start: April 1, 2019
• Primary Completion: September 30, 2022
• Study Completion: April 23, 2024
• Last Updated: August 3, 2025
• Results First Posted: July 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CO (1)