Study of the Molecular Mechanisms Underlying the Cross-neutralizing Capacity of AS04-adjuvanted HPV Vaccine (Cervarix®) in Comparison With the Aluminiumhydroxyphosphate Sulphate Adjuvanted HPV Vaccine (Gardasil®)

NCT01914367 | Completed Phase 4

• 2 other identifiers: 2013/4222013-002340-90
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Six identical female twins aged 9-13 years will participate. One sib of each twin pair will be given Cervarix according to the 0, 1, 6 month vaccination scheme, while the other sib will be given Gardasil according to the 0, 2, 6 month vaccination scheme. Three blood samples will be taken (the first prior to vaccine administration, the second and third 7 days after dose 2 and 3, respectively). The blood samples will be used to determine: 1) the magnitude the anti-HPV 16 and anti-HPV-18 antibody responses, 2) as well as the cross-reactive pattern of these responses towards related, non-vaccine HPV strains (HPV-31 and -33, and HPV-45). 3) plasmablast isolated from blood taken 7 days after the 3rd dose in the first place (and eventually after the 2nd dose also) will be examined for for the usage of VDJ and VJ segments in the immunoglobulin heavy (VH) and light (VL) heavy and light chains. Gene useg in B cells induced by Cervarix and Gardasil will be compared. Finally the cross-reactive potential of monoclonal antibodies obtained by eukaryotic expression of a series of heavy (VH) and light (VL) chains from single ASC isolated after the 3rd dose of a three-dose schedule of either Cervarix or Gardasil will be examined. The duration of the study is approximately 187 days. Five study visits will take place, over a time period of 6.5 months, followed by a telephone call after 12 months. The purpose of the study is to learn more about the molecular mechanisms underlying the cross-neutralizing capacity of AS04-adjuvanted HPV vaccine (Cervarix®) in comparison with the aluminiumhydroxyphosphate sulphate adjuvanted HPV vaccine (Gardasil®).

Conditions

Infection With Human Papillomavirus

Outcome Measures

Primary Outcomes (2)

• comparing of VDJ and VJ segments in the immunoglobulin heavy and light chains/plasmablasts

  at day 187

• comparing the mutational diversity that occurs following vaccine-induced affinity maturation in plasmablasts

  at day 187

Secondary Outcomes (3)

• evaluation of the cross-reactive pattern of polyclonal serum antibodies

  at day 187

• comparing of VDJ and VJ segment usage and affinity maturation in HPV-specific antibodies

  at day 187

• comparing of the cross-reactive potential of monoclonal antibodies obtained by eukaryotic expression of a series of heavy (VH) and light (VL) chains from single ASC

  at day 187

Study Arms (2)

Cervarix group

ACTIVE COMPARATOR

One sib of each twin pair will be given Cervarix according to the 0, 1, 6 month vaccination scheme.

Biological: cervarix

Gardasil Group

ACTIVE COMPARATOR

One sib of each twin pair will be given Gardasil according to the 0, 1, 6 month vaccination scheme.

Biological: Gardasil

Interventions

cervarix BIOLOGICAL

3 doses will be given, one on Day 0, one on Day 30 and one on Day 180 ± 7 days, intramuscular in the deltoid muscle of the non-dominant arm

Also known as: GSK's commercially available bivalent HPV types 16 and 18 recombinant vaccine containing AS04 adjuvant (Cervarix®)

Cervarix group

Gardasil BIOLOGICAL

3 doses will be given, one on Day 0, one on Day 60 ± 2 days and one on Day 180 ± 7 days, intramuscular in the deltoid muscle of the non-dominant arm

Also known as: Merck's commercially availably quadrivalent HPV(types 6, 11, 16, 18) recombinant vaccine containing amorphous aluminiumhydroxyphosphate sulphate adjuvant

Gardasil Group

Eligibility Criteria

• Age: 9 Years - 13 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Six homozygous twins in good health, without preceding sexual activity (virgin). Subjects have a negative pregnancy test on the day of vaccination and have agreed to continue abstinence during the entire study period and for two months after completion of the vaccination series.

You may not qualify if:

• Subjects are not participating in any other clinical trials and have not been vaccinated previously against HPV and have not had an administration of MPL or AS04 in the past.

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

Ghent University Hospital

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Geert Leroux-Roels, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 6, 2013
• First Posted: August 2, 2013
• Study Start: June 25, 2013
• Primary Completion: September 23, 2015
• Study Completion: September 23, 2015
• Last Updated: December 9, 2022

Record last verified: 2022-12

Locations

BE (1)