Clinical trial NCT00501137: A Controlled Trial to Assess the Immunogenicity of a Proposed Paediatric Dosing Schedule of Human Papillomavirus Vaccine
Official title: A Controlled Trial to Assess the Immunogenicity of a Proposed Paediatric Dosing Schedule of Human Papillomavirus Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Cancer
Genital Warts
Keywords: HPV
HPV vaccine
Gardasil
Human Papillomavirus
vaccine
2 dose versus 3
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Ministry of Health, British Columbia
First posted: 2007-07-13
Enrollment: 830
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 26
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary objective is to determine if antibody responses to HPV types 16 \& 18 are non-inferior after a 2-dose paediatric regimen as compared to a 3-dose adult regimen of Q-HPV vaccination, with responses measured at Month 7.

Detailed description: Human Papillomavirus (HPV) infection is a cause of cervical cancer. Immunogenicity, safety and efficacy in the prevention of persistent infection from HPV 16 and 18 has been proven using a 3-dose regimen in adolescent and adult females using the Quadrivalent Human Papillomavirus (Q-HPV) vaccine. The intensity of the immune response is inversely proportional to age. Immunogenicity in adolescents 9-15 years of age is 1.7 - 2 times greater than in 16-26 year old vaccine recipients. Paediatric dosing studies are necessary and prudent given limited provincial funding for new biologics acquisition and programme service delivery. A reduction from an adult 3-dose HPV vaccine regimen to a pediatric 2-dose regimen will result in increased compliance to the full vaccine series and in significant savings to the health care system both in the cost of biologics and of program delivery and administration.

Eligibility criteria: Inclusion Criteria:

* A female between, and including, 9-13 years (before 14th birthday) and 16-26 years of age (before 27th birthday) at the time of the first vaccination.
* Healthy
* Not pregnant
* Four or less sexual partners over lifetime as reported by subject. (Sexual activity is defined as intercourse)
* Not planning to become pregnant or likely to become pregnant
* No reported history of genital warts
* No laboratory confirmed history of cervical intraepithelial neoplasia
* No previous vaccination against HPV
* No administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
* No previous anaphylactic reaction to HPV vaccine or any vaccine related component including aluminum hydroxyphosphate sulfate and polysorbate 80
* No confirmed or suspected immunosuppressive or immunodeficient condition based on medical history
* No bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
* Cannot be already enrolled in any clinical trial in which investigational vaccine or drug are being administered

Exclusion Criteria

* Pregnant
* Female planning to become pregnant or likely to become pregnant (as determined by the investigator) during the study duration Part 1 (0-7 months)
* Reported history of genital warts
* Laboratory confirmed history of cervical intraepithelial neoplasia
* Greater than four lifetime sexual partners involving sexual intercourse
* Previous vaccination against HPV
* Administration of immunoglobulin and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
* A previous anaphylactic reaction to HPV vaccine or any vaccine related component including aluminum hydroxyphosphate sulfate and polysorbate 80
* Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history (e.g. HIV infection, genetic defect, immunosuppressive therapy). \*Chronic administration (defined as more than 14 days) of immune-modifying drugs within 6 months prior to the first vaccine dose or planned use during the study period is exclusionary (corticosteroid use - immune-modifying level is ≥0.5 mg/kg/day; inhaled or topical steroids are acceptable).
* Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection (thrombocytopaenia, coagulation disorder, anti-coagulant therapy).
* Enrollment in any clinical trial in which investigational vaccine or drug are being administered

Primary outcomes:
measure: Primary Objective Part 1
timeFrame: Measured after Month 7
measure: Primary Objective Part 2
timeFrame: At 18, 24 and 36mths post dose 1
measure: Primary Objective Part 2
timeFrame: Measured at 36 mths
Secondary outcomes:
measure: Secondary Objective Part 1 & 2 - Antibody responses 2 doses between 9-13 vs 16-26
timeFrame: Measured at 7, 18,24 and 36 mths
measure: Secondary Objective Part 1 & 2 - HPV 16 and 18 2 doses versus 3
timeFrame: Measured at 7,18,24 and 36 mths
measure: Secondary Objective Part 1 seroconversion rates
timeFrame: Measured at 7 mths
measure: Secondary Objective Part 1 Memory Response
timeFrame: Measured at 7 mths
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Vaccine Evaluation Centre
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Simon Dobson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vaccine Evaluation Centre, Vancouver
name: David Scheifele, MD
role: STUDY_DIRECTOR
affiliation: Vaccine Evaluation Centre, Vancouver
name: Meena Dawar, MD
role: STUDY_DIRECTOR
affiliation: Vaccine Evaluation Centre, Vancouver
name: Tobias Kollman, MD
role: STUDY_DIRECTOR
affiliation: Centre for Vaccinology, Halifax
name: Shelly McNeil, MD
role: STUDY_DIRECTOR
affiliation: Centre for Vaccinology, Halifax
name: Scott Halperin, MD
role: STUDY_DIRECTOR
affiliation: Centre for Vaccinology, Halifax
name: Joanne Langley, MD
role: STUDY_DIRECTOR
affiliation: Centre de Recherche du CHUL (CHUQ), Quebec
name: Marc Dionne, MD
role: STUDY_DIRECTOR
References:
citation: Dobson SR, McNeil S, Dionne M, Dawar M, Ogilvie G, Krajden M, Sauvageau C, Scheifele DW, Kollmann TR, Halperin SA, Langley JM, Bettinger JA, Singer J, Money D, Miller D, Naus M, Marra F, Young E. Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial. JAMA. 2013 May 1;309(17):1793-802. doi: 10.1001/jama.2013.1625.
citation: Krajden M, Cook D, Yu A, Chow R, Su Q, Mei W, McNeil S, Money D, Dionne M, Palefsky J, Karunakaran K, Kollmann T, Ogilvie G, Petric M, Dobson S. Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization, Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial. Vaccine. 2014 Jan 23;32(5):624-30. doi: 10.1016/j.vaccine.2013.09.007. Epub 2013 Sep 19.
citation: Krajden M, Cook D, Yu A, Chow R, Mei W, McNeil S, Money D, Dionne M, Karunakaran KP, Palefsky JM, Dobson S, Ogilvie G, Petric M. Human papillomavirus 16 (HPV 16) and HPV 18 antibody responses measured by pseudovirus neutralization and competitive Luminex assays in a two- versus three-dose HPV vaccine trial. Clin Vaccine Immunol. 2011 Mar;18(3):418-23. doi: 10.1128/CVI.00489-10. Epub 2011 Jan 19.
citation: Smolen KK, Gelinas L, Franzen L, Dobson S, Dawar M, Ogilvie G, Krajden M, Fortuno ES 3rd, Kollmann TR. Age of recipient and number of doses differentially impact human B and T cell immune memory responses to HPV vaccination. Vaccine. 2012 May 21;30(24):3572-9. doi: 10.1016/j.vaccine.2012.03.051. Epub 2012 Mar 31.