Comparing One or Two Doses of the Human Papillomavirus Vaccine for the Prevention of Human Papillomavirus Infection, ESCUDDO Study

NCT03180034 | Active Not Recruiting Phase 4 DMC

• 3 other identifiers: NCI-2020-08550CEC-HCB-E006-202417-C-N108
• Study Type: interventional
• Target: 27,945
• Locations: 1 country
• Sites: 1

Brief Summary

This phase IV trial investigates whether one dose of a human papillomavirus vaccine works as well as two doses in preventing human papillomavirus (HPV) infection. Certain types of HPV cause almost all cases of cervical cancer. Vaccines that protect against infection with these types of human papillomavirus may reduce the risk of cervical cancer. Both Gardasil-9 and Cervarix protect against HPV 16 and 18, which cause 70% of all cervical cancers. However, HPV vaccination rates are too low, especially in countries with very high rates of cervical cancer. HPV vaccines are expensive-many countries cannot afford them-more than one dose is needed, and giving multiple doses is difficult. Researchers want to find out if one dose prevents HPV infection. If it does, more people might get the vaccine.

Conditions

Human Papillomavirus Infection; Human Papillomavirus-Related Cervical Carcinoma

Outcome Measures

Primary Outcomes (3)

• Occurrence of at least one incident persistent human papillomavirus (HPV)-16 and/or HPV-18 cervical infections, counted cumulatively over the follow-up visits

  To be considered incident and persistent, an HPV-16 and/or HPV-18 infection must fulfill the following criteria: Two same-type HPV positive (by polymerase chain reaction \[PCR\]) test results 3+ months apart at consecutive study visits reported after the 6-month visit (i.e. 12-month visit or later); type-specific HPV negative results from baseline and 6 month visits.

  Months 12 to 60

• Incident persistent HPV-16 and/or HPV-18 cervical infections

  Same type infection at 54 and 60-month visits, and absence of infection at the both 0- and 6-month visits.

  Months 54 and 60

• Persistent HPV-16 and/or HPV-18 cervical infections (End-of-Study Survey Cohort)

  Baseline, and 6 months

Secondary Outcomes (2)

• HPV-16 and HPV-18 antibody concentration based on the Luminex bead-based multiplex immunoassay (LIA) assay

  Up to 36 months

• Incident-persistent HPV infections, defined similarly as the primary outcomes, but in different groupings of HPV types

  Months 12 to 60

Study Arms (5)

Arm I (Gardasil, Tdap)

EXPERIMENTAL

Participants receive Gardasil IM at month 0 and Tdap IM at month 6.

Biological: Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed; Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Arm II (Cervarix, Tdap)

EXPERIMENTAL

Participants receive Cervarix IM at month 0 and Tdap IM at month 6.

Biological: Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed; Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Bivalent Vaccine

Arm III (Gardasil)

ACTIVE COMPARATOR

Participants receive Gardasil IM at month 0 and 6.

Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Nonavalent Vaccine

Arm IV (Cervarix)

ACTIVE COMPARATOR

Participants receive Cervarix IM at month 0 and 6.

Other: Questionnaire Administration; Biological: Recombinant Human Papillomavirus Bivalent Vaccine

Arm V (epidemiologic survey)

NO INTERVENTION

A concurrent epidemiologic survey for HPV status among two groups of unvaccinated women. Survey participants are followed for two study visits six months apart to determine their HPV DNA status, with no further follow-up. These women will be offered HPV vaccination (Cervarix) at the two study visits.

Interventions

Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed BIOLOGICAL

Given IM

Also known as: Adacel, Daptacel, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed, Diphtheria Toxoid Tetanus Toxoid Acellular Pertussis Vaccine Adsorbed, Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine, DTaP, Infanrix, Tripedia

Arm I (Gardasil, Tdap); Arm II (Cervarix, Tdap)

Questionnaire Administration OTHER

Ancillary studies

Arm I (Gardasil, Tdap); Arm II (Cervarix, Tdap); Arm III (Gardasil); Arm IV (Cervarix)

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

Arm II (Cervarix, Tdap); Arm IV (Cervarix)

Recombinant Human Papillomavirus Nonavalent Vaccine BIOLOGICAL

Given IM

Also known as: Gardasil 9, Nonavalent HPV VLP Vaccine, Recombinant HPV Nonavalent Vaccine, Recombinant Human Papillomavirus 9-valent Vaccine

Arm I (Gardasil, Tdap); Arm III (Gardasil)

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Female
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Aged between 12 and 16 years inclusive
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Living in the study area without plans to move outside the country in the next six months
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Able to communicate with study personnel
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Willing to participate in the study and sign the informed assent
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: Supported in study participation by at least one of their parents (or guardians), who is willing to sign the informed consent document
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: In good health as determined by a medical history (physical exam will be conducted if necessary per the doctor's criterion)
• INITIAL SURVEY ELIGIBILITY CRITERIA: Same as trial participants except for the age range, which is between 17 and 20 years old inclusive
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: Same as trial and initial survey participants except for the age range, which will be closely matched to the current ages of trial participants when they are attending their E54 visits, and thus is expected to be approximately between 16 and 21 years old inclusive

You may not qualify if:

• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: 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
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: They are allergic to one of the vaccine components, yeast, or latex
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: The clinician determining the eligibility in agreement with principal investigator considers that there is a reason that precludes participation
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: They have been vaccinated against HPV
• RANDOMIZED TRIAL ELIGIBILITY CRITERIA: The girl or her parent/legal guardian does not have an identification document
• INITIAL SURVEY ELIGIBILITY CRITERIA: Same as trial participants
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They have a positive or equivocal urine pregnancy test result
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They are pregnant
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: investigator considers that there is a reason that precludes participation
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They have been vaccinated against HPV
• END-OF-STUDY SURVEY ELIGIBILITY CRITERIA: They or their parent/legal guardian, as applicable, does not have an identification document

Sponsors & Collaborators

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

Study Sites (1)

Agencia Costarricense de Investigaciones Biomédicas (ACIB)

Liberia, Guanacaste Province, 50101, Costa Rica

Location

Related Publications (5)

• Kreimer AR, Porras C, Liu D, Hildesheim A, Carvajal LJ, Ocampo R, Romero B, Gail MH, Cortes B, Sierra MS, Coronado K, Sampson J, Coto C, Dagnall CL, Mora D, Kemp TJ, Zuniga M, Pinto LA, Barrientos G, Schussler J, Estrada Y, Montero C, Avila C, Ruggieri D, Cyr JT, Chanock S, Lowy DR, Schiller JT, Herrero R. Noninferiority of One HPV Vaccine Dose to Two Doses. N Engl J Med. 2025 Dec 18;393(24):2421-2433. doi: 10.1056/NEJMoa2506765. Epub 2025 Dec 3.

  PMID: 41337735 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.

  PMID: 41276263 DERIVED

• Porras C, Sampson JN, Herrero R, Gail MH, Cortes B, Hildesheim A, Cyr J, Romero B, Schiller JT, Montero C, Pinto LA, Schussler J, Coronado K, Sierra MS, Kim JJ, Torres CM, Carvajal L, Wagner S, Campos NG, Ocampo R, Kemp TJ, Zuniga M, Lowy DR, Avila C, Chanock S, Castrillo A, Estrada Y, Barrientos G, Monge C, Oconitrillo MY, Kreimer AR. Rationale and design of a double-blind randomized non-inferiority clinical trial to evaluate one or two doses of vaccine against human papillomavirus including an epidemiologic survey to estimate vaccine efficacy: The Costa Rica ESCUDDO trial. Vaccine. 2022 Jan 3;40(1):76-88. doi: 10.1016/j.vaccine.2021.11.041. Epub 2021 Nov 29.

  PMID: 34857420 DERIVED

• Teppler H, Bautista O; Thomas Group; Flores S, McCauley J, Luxembourg A. Design of a Phase III immunogenicity and safety study evaluating two-dose regimens of 9-valent human papillomavirus (9vHPV) vaccine with extended dosing intervals. Contemp Clin Trials. 2021 Jun;105:106403. doi: 10.1016/j.cct.2021.106403. Epub 2021 Apr 12.

  PMID: 33857679 DERIVED

• Kreimer AR, Cernuschi T, Rees H, Saslow D, Porras C, Schiller J. Prioritisation of the human papillomavirus vaccine in a time of constrained supply. Lancet Child Adolesc Health. 2020 May;4(5):349-351. doi: 10.1016/S2352-4642(20)30038-9. Epub 2020 Feb 17. No abstract available.

  PMID: 32078808 DERIVED

MeSH Terms

Conditions

Papillomavirus Infections

Interventions

Diphtheria Toxoid; adacel; Diphtheria-Tetanus-acellular Pertussis Vaccines; Tetanus Toxoid; human papillomavirus vaccine, L1 type 16, 18; Human Papillomavirus Recombinant Vaccine nonavalent

Condition Hierarchy (Ancestors)

Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Communicable Diseases; Infections; DNA Virus Infections; Virus Diseases; Tumor Virus Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Toxoids; Vaccines; Biological Products; Complex Mixtures; Pertussis Vaccine; Bacterial Vaccines; Vaccines, Combined; Vaccines, Acellular; Vaccines, Subunit

Study Officials

• Aimee R Kreimer

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Specimen lab
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 8, 2017
• Study Start: November 29, 2017
• Primary Completion: August 21, 2025
• Study Completion (Estimated): August 1, 2028
• Last Updated: September 4, 2025

Record last verified: 2025-09

Locations

CO (1)