Randomized Trial of Alternative HPV Vaccination Schedules in Males in a University Setting

The investigators propose a randomized, open label trial of the immunogenicity of HPV vaccine among males 18-24 years old, comparing an on-time administration of the third dose with delayed administration of the third dose. All participants would receive the first and second doses according to schedule. They would be randomized to either Dose 3 at 6 months or Dose 3 at 12 months.

Hypothesis: The Geometric mean titers in the 12 month test group (T) are non-inferior to the usual timing control group (C):

H0: δ ≤ -δ0 versus H1: δ > -δ0 where δ = log (GMTT )- log (GMTC) and δ0 is the pre-specified non-inferiority margin

Study Overview

• Status: Completed
• Conditions: Quadrivalent HPV Vaccine; Human Papillomavirus Vaccine
• Intervention / Treatment: Biological: quadrivalent human papillomavirus vaccine; Biological: quadrivalent human papillomavirus vaccine

Detailed Description

1. Specific Aims and Overview: The investigators propose a randomized, open label trial of HPV vaccine among males 18-24 years old, comparing an on-time administration of the third dose with delayed administration of the third dose. All participants would receive the first and second doses according to schedule. They would be randomized to either Dose 3 at 6 months or Dose 3 at 12 months.

Blood would be drawn for titers at twice from all participants: pre-dose 1 and one month post Dose 3.

No cytology studies or DNA studies will be conducted.

1.1 Aims:

1. Determine if delay in the third dose is immunologically non-inferior to the standard administration schedule (1 month post-dose 3).
2. Determine the side effect profile of a delayed third dose, in comparison to the standard schedule.
3. Determine the preference and compliance of the men for the timing of the third dose.

1.2 Hypothesis for non- inferiority:

The GMTs in the test group (T) are non-inferior to the usual timing control group (C):

H0: δ ≤ -δ0 versus H1: δ > -δ0 where δ = log (GMTT )- log (GMTC) and δ0 is the pre-specified non-inferiority margin.

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 26 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males age 18-26

Exclusion Criteria:

• Hospitalization within the past year

• Previous HPV vaccination

  >/=5 sexual partners (i.e., insertive intercourse) No other drug studies within 30 days of proposed HPV vaccination

• History of genital warts
• Immunosuppression
• Other vaccines within 8 days of proposed HPV vaccination
• Hypersensitivity to yeast or HPV vaccine components
• Known autoimmune disorders
• Receipt of immunoglobulins or blood product within 90 days of enrollment (may defer until 90 days completed)
• Serious Adverse Reaction to HPV vaccine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12 months; Administration of 3rd dose at 12 months quadrivalent human papillomavirus vaccine	Biological: quadrivalent human papillomavirus vaccine; 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 12 months; Other Names: Gardasil; Biological: quadrivalent human papillomavirus vaccine; 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 6 months; Other Names: Gardasil
Active Comparator: 6 month; Administration of 3rd dose at 6 months quadrivalent human papillomavirus vaccine	Biological: quadrivalent human papillomavirus vaccine; 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 12 months; Other Names: Gardasil; Biological: quadrivalent human papillomavirus vaccine; 0.5 mL of quadrivalent HPV vaccine at enrollment, 2 months, and 6 months; Other Names: Gardasil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity After Dose 3	Geometric mean titer (GMT) and 95% confidence intervals around titer 1 month after dose 3 in per protocol population, comparing the two groups.	1 month after dose 3 (e.g., month 7 if third dose at 6months or month 13 if third dose at 12 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance With 3rd Dose	Determine the compliance of the men for the timing of the third dose.	at 3rd dose (i.e., at month 6 or month 12, depending on arm)
Safety Profile	Total proportion of side effects reported after any dose, compared by arm.	1 week after vaccination

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Richard K Zimmerman, MD MPH, University of Pittsburgh

Publications and helpful links

General Publications

• Zimmerman RK, Nowalk MP, Lin CJ, Fox DE, Ko FS, Wettick E, Cost G, Hand L, Hayes J, Michaels M. Randomized trial of an alternate human papillomavirus vaccine administration schedule in college-aged women. J Womens Health (Larchmt). 2010 Aug;19(8):1441-7. doi: 10.1089/jwh.2009.1753.
• Lin CJ, Zimmerman RK, Nowalk MP, Huang HH, Raviotta JM. Randomized controlled trial of two dosing schedules for human papillomavirus vaccination among college age males. Vaccine. 2014 Feb 3;32(6):693-9. doi: 10.1016/j.vaccine.2013.11.098. Epub 2013 Dec 14.
• Zimmerman RK, Lin CJ, Raviotta JM, Nowalk MP. Do vitamin D levels affect antibody titers produced in response to HPV vaccine? Hum Vaccin Immunother. 2015;11(10):2345-9. doi: 10.1080/21645515.2015.1062955.

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 17, 2010
• First Posted (Estimate): August 18, 2010

Study Record Updates

• Last Update Posted (Estimate): March 27, 2014
• Last Update Submitted That Met QC Criteria: February 26, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: human papillomavirus vaccine L1, type 6,11,16,18; HPV Vaccines; HPV L1 vaccine, quadrivalent 6,11,16,18
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: IISP#38206; PRO10070407 (Other Identifier: University of Pittsburgh IRB); I#0021806 (Other Identifier: University of Pittsburgh InfoEd)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No