An Exploratory Open-Label Clinical Trial Evaluating the Immunogenicity of the 9-valent 2-dose HPV Vaccination Regimen

NCT04206813 | Active Not Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: H-39051
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to explore and evaluate whether a 2-dose schedule of Gardasil 9 among young and mid-adult women 16-45 years of age is generally safe and immunogenic, with an antibody response that is not inferior to that observed of a 3-dose schedule of Gardasil 9 among women aged 16-26 years old. The investigators thought that having a 2-dose vaccination regimen for individuals 16 to 45 would provide a more robust dataset than those of 27 to 45 years old.

Conditions

HPV Infection

Keywords

Gardasil; Immunogenicity; 9-valent 2-dose HPV vaccination; 9-valent 3-dose HPV vaccination

Outcome Measures

Primary Outcomes (2)

• Change in immunogenicity of Gardasil 9

  Immunogenicity will be measured by serum antibodies assessed by ELISA to the nine HPV types (anti-HPV 6/11/16/18/31/33/45/ 52/58 where positive anti-HPV serum levels are defined as \>30, \>16, \>20, \>24, \>10, \>8, \>8, \>8, or \>8 milli Merck units (mMU)/mL respectively).

  baseline and 7 months

• Change in geometric mean titers ratios

  The geometric mean titers (GMT) ratios will be determined by a post-vaccination geometric mean titer (GMT) ratio with a pre-stated analysis of variance model (95% Confidence Interval lower bound \>0.5).

  baseline and 7 months

Secondary Outcomes (2)

• Number of participants with HPV seropositivity at day 1

  day 1

• Number of participants with HPV seropositivity at month 7

  month 7

Study Arms (2)

Intervention group

EXPERIMENTAL

240 eligible women will receive a 2-dose regimen of Gardasil 9 at (0 and 6 months, followed by a rescue 3rd dose at month 12)

Drug: Gardasil 9 2 dose regimen; Drug: Gardasil 9 rescue dose

Control group

ACTIVE COMPARATOR

120 eligible women will receive the standard 3-dose regimen of Gardasil 9 at (0, 2, 6 months)

Drug: Gardasil 9 3 dose regimen

Interventions

Gardasil 9 3 dose regimen DRUG

standard 3-dose regimen of Gardasil 9 at 0, 2, 6 months

Also known as: Human Papillomavirus 9-valent Vaccine, Recombinant

Control group

Gardasil 9 rescue dose DRUG

A rescue dose of Gardasil 9 will be given at 12 months

Also known as: Human Papillomavirus 9-valent Vaccine, Recombinant

Intervention group

Gardasil 9 2 dose regimen DRUG

a 2-dose regimen of Gardasil 9 at 0 and 6 months

Also known as: Human Papillomavirus 9-valent Vaccine, Recombinant

Intervention group

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Women receiving care at Boston Medical Center

You may not qualify if:

• Currently pregnant
• Prior HPV vaccination
• A history of severe allergic reaction, including known allergy to any vaccine component, specially severe allergic to yeast
• Immunocompromised/previous immunosuppressive therapy
• Thrombocytopenia or other coagulation disorder
• Currently breastfeeding

Sponsors & Collaborators

• Boston Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Related Publications (11)

• Meites E, Kempe A, Markowitz LE. Use of a 2-Dose Schedule for Human Papillomavirus Vaccination - Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016 Dec 16;65(49):1405-1408. doi: 10.15585/mmwr.mm6549a5.

  PMID: 27977643 BACKGROUND

• Joura EA, Giuliano AR, Iversen OE, Bouchard C, Mao C, Mehlsen J, Moreira ED Jr, Ngan Y, Petersen LK, Lazcano-Ponce E, Pitisuttithum P, Restrepo JA, Stuart G, Woelber L, Yang YC, Cuzick J, Garland SM, Huh W, Kjaer SK, Bautista OM, Chan IS, Chen J, Gesser R, Moeller E, Ritter M, Vuocolo S, Luxembourg A; Broad Spectrum HPV Vaccine Study. A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women. N Engl J Med. 2015 Feb 19;372(8):711-23. doi: 10.1056/NEJMoa1405044.

  PMID: 25693011 BACKGROUND

• Castellsague X, Munoz N, Pitisuttithum P, Ferris D, Monsonego J, Ault K, Luna J, Myers E, Mallary S, Bautista OM, Bryan J, Vuocolo S, Haupt RM, Saah A. End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age. Br J Cancer. 2011 Jun 28;105(1):28-37. doi: 10.1038/bjc.2011.185. Epub 2011 May 31.

  PMID: 21629249 BACKGROUND

• Giuliano AR, Isaacs-Soriano K, Torres BN, Abrahamsen M, Ingles DJ, Sirak BA, Quiterio M, Lazcano-Ponce E. Immunogenicity and safety of Gardasil among mid-adult aged men (27-45 years)--The MAM Study. Vaccine. 2015 Oct 13;33(42):5640-5646. doi: 10.1016/j.vaccine.2015.08.072. Epub 2015 Sep 4.

  PMID: 26343499 BACKGROUND

• Romanowski B, Schwarz TF, Ferguson LM, Peters K, Dionne M, Schulze K, Ramjattan B, Hillemanns P, Catteau G, Dobbelaere K, Schuind A, Descamps D. Immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine administered as a 2-dose schedule compared with the licensed 3-dose schedule: results from a randomized study. Hum Vaccin. 2011 Dec;7(12):1374-86. doi: 10.4161/hv.7.12.18322. Epub 2011 Dec 1.

  PMID: 22048171 BACKGROUND

• Basu P, Muwonge R, Bhatla N, Nene BM, Joshi S, Esmy PO, Poli URR, Joshi G, Verma Y, Zomawia E, Shastri SS, Pimple S, Anantharaman D, Prabhu PR, Hingmire S, Sauvaget C, Lucas E, Pawlita M, Gheit T, Jayant K, Malvi SG, Siddiqi M, Michel A, Butt J, Sankaran S, Rameshwari Ammal Kannan TP, Varghese R, Divate U, Willhauck-Fleckenstein M, Waterboer T, Muller M, Sehr P, Vashist S, Mishra G, Jadhav R, Thorat R, Tommasino M, Pillai MR, Sankaranarayanan R; Indian HPV vaccine study group. Two-dose recommendation for Human Papillomavirus vaccine can be extended up to 18 years - updated evidence from Indian follow-up cohort study. Papillomavirus Res. 2019 Jun;7:75-81. doi: 10.1016/j.pvr.2019.01.004. Epub 2019 Jan 31.

  PMID: 30711698 BACKGROUND

• Meites E, Szilagyi PG, Chesson HW, Unger ER, Romero JR, Markowitz LE. Human Papillomavirus Vaccination for Adults: Updated Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2019 Aug 16;68(32):698-702. doi: 10.15585/mmwr.mm6832a3.

  PMID: 31415491 BACKGROUND

• Hernandez-Avila M, Torres-Ibarra L, Stanley M, Salmeron J, Cruz-Valdez A, Munoz N, Herrero R, Villasenor-Ruiz IF, Lazcano-Ponce E. Evaluation of the immunogenicity of the quadrivalent HPV vaccine using 2 versus 3 doses at month 21: An epidemiological surveillance mechanism for alternate vaccination schemes. Hum Vaccin Immunother. 2016;12(1):30-8. doi: 10.1080/21645515.2015.1058458. Epub 2015 Jul 25.

  PMID: 26211489 BACKGROUND

• Block SL, Nolan T, Sattler C, Barr E, Giacoletti KE, Marchant CD, Castellsague X, Rusche SA, Lukac S, Bryan JT, Cavanaugh PF Jr, Reisinger KS; Protocol 016 Study Group. Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women. Pediatrics. 2006 Nov;118(5):2135-45. doi: 10.1542/peds.2006-0461.

  PMID: 17079588 BACKGROUND

• Van Damme P, Olsson SE, Block S, Castellsague X, Gray GE, Herrera T, Huang LM, Kim DS, Pitisuttithum P, Chen J, Christiano S, Maansson R, Moeller E, Sun X, Vuocolo S, Luxembourg A. Immunogenicity and Safety of a 9-Valent HPV Vaccine. Pediatrics. 2015 Jul;136(1):e28-39. doi: 10.1542/peds.2014-3745.

  PMID: 26101366 BACKGROUND

• Yifan Huang, Jason C. Hsu, Hochberg's Step-Up Method: Cutting Corners Off Holm's Step-Down Method, Biometrika, Volume 94, Issue 4, December 2007, Pages 965-975, https://doi.org/10.1093/biomet/asm067

  BACKGROUND

Related Links

• Centers for Disease Control and Prevention, Human Papillomavirus (HPV) facts.
• Centers for Disease Control and Prevention, on how many cancers are linked with HPV each year.
• Merck Sharp \& Dohme Corp. An Open-Label Phase III Clinical Trial to Study the Immunogenicity and Tolerability of GARDASIL®9 (A Multivalent Human Papillomavirus \[HPV\] L1 Virus-Like Particle Vaccine) in Adult Women Compared to Young Adult Women
• Food and Drug Administration. Prescribing information \[package insert\]. Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant).
• Luxembourg A. 9vHPV immunogenicity and safety trial in mid-adult females. Advisory Committee on Immunization Practices (ACIP).
• Implementing Constrained or Balanced-Across-the-Centers Randomization with SAS v8 Procedure PLAN Song CQ.

MeSH Terms

Conditions

Papillomavirus Infections

Interventions

Human Papillomavirus Recombinant Vaccine nonavalent; Clinical Protocols

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)

Therapeutics; Epidemiologic Study Characteristics; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation

Study Officials

• Carl G Streed, MD MPH

  Boston Medical Center, Internal Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The control group will have 120 subjects will receive a 3-dose regimen as recommended by Center for Disease Control (CDC) given at 0, 2 and 6 months. The intervention group will have 240 subjects who will receive a modified 3-dose regimen given at 0, 6, and 12 months. Both groups will have HPV titers drawn at Visit 1 (pre-vaccination) and Visit 7 (after three doses for the Control group and 2 doses for the Intervention group).

Study Record Dates

• First Submitted: December 15, 2019
• First Posted: December 20, 2019
• Study Start: December 1, 2020
• Primary Completion: April 15, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)