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Trial registered on ANZCTR


Registration number
ACTRN12608000339358
Ethics application status
Approved
Date submitted
16/05/2008
Date registered
18/07/2008
Date last updated
9/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot efficacy bridging study of two human papillomavirus vaccines administered intradermally and intramuscularly
Scientific title
A pilot non-inferiority immunogenicity single blind randomised study of two human papillomavirus vaccines administered intradermally to females aged 18 to 26 years to bridge previous efficacy findings of intramuscularly administered vaccine
Secondary ID [1] 252969 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Human papilloma virus (HPV) infection 3157 0
Condition category
Condition code
Infection 3315 3315 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A total of 40 female subjects aged 18-26y at the start of the study will be enrolled. After consent, all subjects will have blood taken for serum antibody to HPV16 and HPV18. Those subjects who test negative for both HPV16 and HPV18 will be randomised, using simple randomisation. Subjects will be vaccinated on Day 1, Month 2 (+/- 2 weeks) and Month 6 (+/- 2 weeks). Five subjects for each vaccine type will receive full dose (0.5ml) intramuscularly, five will receive 20% (0.1ml) of the full dose intramuscularly, five will receive a 20% (0.1ml) of full dose intradermally via an intradermal injection device, and five will receive 20% (0.1ml) of full dose intradermally with a tuberculin syringe and needle for all three vaccine doses. An equal number of subjects will receive Gardasil and Cervarix. As this study involves three clearly identifiable routes of administration for the two vaccines, this will not be a double-blind study. Prior to starting the main study a 20%-dose of Cervavix vaccine (0.1-ml) and a 20%-dose of Gardasil vaccine (0.1-ml) will each be given intradermally via syringe and needle to ten adult males with 5 subjects receiving each vaccine to ensure that no unexpectedly severe reactions occur with the Cervavix vaccine which contains a novel adjuvant (ASO4) that has not been administered intradermally before and could be more reactogenic than vaccines such as Gardasil containing traditional alum adjuvants. Subjects in this reactogenicity assessment will complete Diary Cards, undergo two blood tests and photographs of the skin reactions will be taken.
Intervention code [1] 2890 0
Prevention
Comparator / control treatment
Different vaccine (Gardasil and Cervarix), vaccine dose (full dose and 20% of full dose) and vaccine administration route (intramuscular, intradermal with injection device, intradermal with needle and syringe)
Control group
Dose comparison

Outcomes
Primary outcome [1] 4206 0
Proportion of subjects receiving a reduced-dose intradermal schedule, that have a type-specific antibody response to the human papilloma virus vaccine 30 days after the third (month 6) vaccination, that is non-inferior to the type-specific antibody response of those subjects receiving a full-dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates.
Timepoint [1] 4206 0
7 months after 1st vaccination
Secondary outcome [1] 7113 0
Safety: Proportion of subjects with systemic reactions after the first, second and third vaccination
Timepoint [1] 7113 0
1 month, 3 months and 7 months
Secondary outcome [2] 7114 0
Safety: Proportion of subjects with administration site reactions after the first, second and third vaccination
Timepoint [2] 7114 0
1 month, 3 months and 7 months
Secondary outcome [3] 7115 0
Safety: Frequency and severity of occurrence of severe adverse events observed during the entire study period.
Timepoint [3] 7115 0
Information will be sought at least monthly from study subjects about any severe adverse event occuring during the study period from 0 to 7 months
Secondary outcome [4] 7116 0
Immunogenicity: Proportion of subjects receiving a reduced-dose intradermal schedule, that have a type-specific antibody response to the human papilloma virus vaccine 30 days after the first (day 1) vaccination, that is non-inferior to the type-specific antibody response of those subjects receiving a full-dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates.
Timepoint [4] 7116 0
1 month
Secondary outcome [5] 7117 0
Immunogenicity: Proportion of subjects receiving a reduced-dose intradermal schedule, that have a type-specific antibody response to the human papilloma virus vaccine 30 days after the second (month 2) vaccination, that is non-inferior to the type-specific antibody response of those subjects receiving a full-dose intramuscular schedule of the vaccine. The antibody response will be defined by geometric mean titres and seroconversion rates.
Timepoint [5] 7117 0
3 months
Secondary outcome [6] 7118 0
Immunogenicity: Compare the levels of type-specific antibody response developed following administration of the two different vaccines after the first, second and third vaccinations.
Timepoint [6] 7118 0
1 month, 3 months and 7 months
Secondary outcome [7] 7119 0
Immunogenicity: Compare the levels of type-specific antibody response developed following administration of the two different vaccines given by the two different intradermal methods (jet injector and 30 gauge needle/syringe) after the first, second and third vaccinations.
Timepoint [7] 7119 0
1 month, 3 months and 7 months

Eligibility
Key inclusion criteria
Female subjects will be eligible to participate in the study if they: 1. Are 18-26 years of age at the start of the study; 2. Participants have an understanding of the study, agree to its requirements, and give written informed consent prior to study entry; 3. Are generally healthy; 4. Agree to keep a record of symptoms for 14 days after each vaccination; 5. Are sexually naive.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Have previously received HPV vaccine 2. Test positive for either HPV 16/18 serum antibody at enrolment; 3. Are not sexually naive at enrollment; 4. Do not agree to use effective contraception if become sexually active; 5. Are allergic to any vaccine component 6. Have received blood products or components during the previous 6-months 7. Have any known immune or coagulation disorder 8. Received any inactivated vaccine product within the 14 days before enrolment 9. Received any live vaccine product within 21 days before enrolment.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
A total of 40 female subjects who meet the inclusion and exclusion criteria, and who can provide written informed consent, will be eligible to be included in the study. After obtaining consent, subjects will select an opaque sealed envelope containing a 4 digit random number. For the main study subjects will not be told which vaccine they have received and for those receiving the vaccine intramuscularly they will not be told whether the dose is full dose or 20% of full dose. Subjects will however be aware whether they have received the vaccine intradermally with either a syringe and needle or with an injection device. The initial 10 subjects participating in the reactogenicity assessment will also not be told which vaccine they have received.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
For the initial reactogenicity study of 10 subjects, simple randomisation using random numbers created by computer software will be used. The subjects will select an envelope containing a 4 digit number. The nurse administering the vaccine will then use a separate list to match this number to a vaccine (either Gardasil or Cervarix). The nurse will not inform the study subject which vaccine was given and the nurse will not be responsible for following-up the subjects. For the main study of 40 subjects, simple randomisation using random numbers created by computer software will also be used. The 40 subjects aged 18-26y will be randomised into one of 8 groups by the subjects selecting an opaque envelope containing a 4 digit random number. The nurse administering the vaccine will use a separate list to match the number to a vaccine (Gardasil or Cervarix), to a dose (full dose or 20% of full dose) and to a route of administration (intramuscular, intradermal by injection device or intradermal by needle and syringe). The nurse administering the vaccine will not inform the subject which vaccine has been given and the nurse will not be responsible for following up the subjects.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
As this study involves three clearly identifiable routes of administration for the two vaccines, this will not be a double-blind study. However subjects will not be informed which vaccine or which intramuscular dose they have received.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/07/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment outside Australia
Country [1] 969 0
Hong Kong
State/province [1] 969 0

Funding & Sponsors
Funding source category [1] 3387 0
Self funded/Unfunded
Name [1] 3387 0
Country [1] 3387 0
Hong Kong
Primary sponsor type
University
Name
The Chinese University of Hong Kong
Address
Department of Paediatrics
The Chinese University of Hong
6F Clinical Science Building
Prince of Wales Hospital
Shatin
Country
Hong Kong
Secondary sponsor category [1] 3032 0
None
Name [1] 3032 0
Address [1] 3032 0
Country [1] 3032 0
Other collaborator category [1] 289 0
Commercial sector/Industry
Name [1] 289 0
Pharmajet Inc
Address [1] 289 0
221 Corporate Circle, Suite D
Golden, Colorado, 80401
Country [1] 289 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5418 0
Joint The Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee
Ethics committee address [1] 5418 0
Flat 3C, Block B, Staff Quarters, Prince of Wales Hospital, Shatin
Ethics committee country [1] 5418 0
Hong Kong
Date submitted for ethics approval [1] 5418 0
09/12/2007
Approval date [1] 5418 0
17/01/2008
Ethics approval number [1] 5418 0
CRE-2007.475-T

Summary
Brief summary
Human papilloma virus (HPV) vaccines have the potential to significantly reduce the problem of cervical cancer and a number of countries have recommended their routine administration. This single blind randomised study will compare two HPV vaccines administered by two different routes (intra-muscularly and intradermally) in different doses. The study aims to demonstrate that a reduced dose of vaccine given intradermally is not inferior in terms of protective antibody response (immunogenicity) to a full dose of vaccine given intra-muscularly. Following an initial reactogenicity study of 10 male subjects, a total of 40 female subjects aged 18 to 26 years will be recruited. As the intradermal route has the potential for easier and safer administration of vaccines, at significantly reduced cost, there is the potential for this study to have significant global implications in terms of making these newer, and relatively expensive, vaccines more widely available.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28594 0
Address 28594 0
Country 28594 0
Phone 28594 0
Fax 28594 0
Email 28594 0
Contact person for public queries
Name 11751 0
Nelson, Edmund Anthony Severn
Address 11751 0
Department of Paediatrics
Prince of Wales Hospital
Shatin
Country 11751 0
Hong Kong
Phone 11751 0
+852 26322849
Fax 11751 0
+852 26360020
Email 11751 0
[email protected]
Contact person for scientific queries
Name 2679 0
Nelson, Edmund Anthony Severn
Address 2679 0
Department of Paediatrics
Prince of Wales Hospital
Shatin
Country 2679 0
Hong Kong
Phone 2679 0
+852 26322849
Fax 2679 0
+852 26360020
Email 2679 0
[email protected]

No information has been provided regarding IPD availability


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No Supporting Document Provided



Results publications and other study-related documents

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