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Trial registered on ANZCTR


Registration number
ACTRN12619000944134
Ethics application status
Approved
Date submitted
11/06/2019
Date registered
5/07/2019
Date last updated
16/07/2019
Date data sharing statement initially provided
5/07/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Pertaprime: A study to assess the immune response and safety of a new pertussis vaccine (Pertagen®) in healthy young adults.
Scientific title
Pertaprime: An investigator-driven phase II-III randomised, observer-blind, controlled trial to demonstrate non-inferior immunogenicity of Pertagen® in comparison to Boostrix® in healthy young Australian adults aged 18-25 years.
Secondary ID [1] 298468 0
Not applicable
Universal Trial Number (UTN)
Not applicable
Trial acronym
Not applicable
Linked study record
Not applicable

Health condition
Health condition(s) or problem(s) studied:
Pertussis prevention 313235 0
Condition category
Condition code
Public Health 311676 311676 0 0
Other public health
Infection 311947 311947 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pertagen® (Pertussis Toxoid 5 µg, Filamentous hemagglutinin 5 µg, Aluminum Hydroxide 0.3 mg/dose (as Al3+), Sodium Chloride 4.38 mg, water for injections quantity sufficient to make up to a volume of 0.5 mL). To be administered as a single 0.5mL dose injected intramuscularly, preferably into the non-dominant deltoid. The vaccine will be administered by appropriately trained study staff (nurses) delegated as unblinded vaccinators.
Intervention code [1] 314708 0
Treatment: Drugs
Comparator / control treatment
Boostrix® (Tetanus Toxoid 5 Limit of flocculation units, Diphtheria Toxoid 2.5 Limit of flocculation units, Pertussis Toxoid 8 µg, Filamentous hemagglutinin 8 µg, Pertactin 2.5 µg, Aluminum Hydroxide 0.3 mg/dose (as Al3+), Aluminium Phosphate 0.2 mg/dose (as Al3+), Sodium Chloride 4.5 mg, water for Injections quantity sufficient to make up to a volume of 0.5 mL). To be administered as a single 0.5mL dose injected intramuscularly, preferably into the non-dominant deltoid. The vaccine will be administered by appropriately trained study staff (nurses) delegated as unblinded vaccinators.
Control group
Active

Outcomes
Primary outcome [1] 320376 0
Composite primary outcome: Seroconversion rates as defined by the proportion of subjects with a greater than or equal to 4-fold increase with respect to baseline of PT (pertussis toxin)-IgG and FHA (filamentous haemagglutinin)-IgG antibodies in Pertagen® and Boostrix® groups in all subjects at day 28 post-vaccination.
Timepoint [1] 320376 0
day 28 post-vaccination.
Secondary outcome [1] 371396 0
Composite secondary outcome: Geometric mean titres (GMTs) of PT-IgG, FHA-IgG and PT neutralization antibodies at Day 28 post-vaccination in all subjects vaccinated with Pertagen® compared to Boostrix®.
Assessed via whole blood sample collection from participants. Measured by standardized Enzyme- Linked ImmunoSorbent Assays (ELISA), validated Multiplex Immune Assays (MIA) or microplate assay.
Timepoint [1] 371396 0
Day 28 post-vaccination.
Secondary outcome [2] 371397 0
Composite secondary outcome: Persistence of GMTs of PT-IgG, FHA-IgG and PT neutralization antibodies 1 year after vaccination in all subjects vaccinated with Pertagen® compared to Boostrix®.
Assessed via whole blood sample collection from participants. Measured by standardized Enzyme- Linked ImmunoSorbent Assays (ELISA), validated Multiplex Immune Assays (MIA) or microplate assay.
Timepoint [2] 371397 0
1 year post-vaccination.
Secondary outcome [3] 371398 0
Seroconversion rates as defined by proportion of subjects with a greater than or equal to 4-fold increase with respect to baseline of PT neutralization antibodies in Pertagen® and Boostrix® groups at day 28 post-vaccination.
Timepoint [3] 371398 0
Day 28 post-vaccination.
Secondary outcome [4] 371399 0
Percentages of subjects with post-vaccination solicited adverse events (local and systemic reactions) until day 8 post-vaccination in the Pertagen® and Boostrix® groups.
Solicited adverse events will be specifically sought for and recorded by participants in the solicited adverse events sections of the visit 1 diary card. Subjects will be issued with the diary card at visit 1 and will be asked to record local and general signs and symptoms on the diary card. All subjects will be provided with a thermometer to measure body temperature, and a small ruler to measure local injection reactions. Solicited local and systemic reactions to be reported by the subject are pre-printed on the Diary Card and consist of: pain, redness, swelling (or induration) at the injection site, and fever, headache, chills, arthralgia, fatigue (or malaise), myalgia, nausea and vomiting.
Timepoint [4] 371399 0
Day 8 post-vaccination.
Secondary outcome [5] 371400 0
Percentages of subjects with reported unsolicited adverse events up to day 28 days post-vaccination in the Pertagen® and Boostrix® groups.
Unsolicited adverse events include adverse events other than those specifically solicited. This includes any other medical events/conditions or changes to the participant's health that may be experienced during this reporting period (regardless of the cause). They will be recorded by the participant in the unsolicited adverse event section of the diary card (ie day 0 to day 27) and by interview with the study staff at visit 2 (if applicable). All adverse events occurring within 28 days following vaccination, will be recorded irrespective of severity or whether or not they are considered vaccination-related.

Timepoint [5] 371400 0
Day 28 post-vaccination.
Secondary outcome [6] 371401 0
Percentages of subjects with any reported serious adverse event (related or unrelated) up to day 28 post-vaccination in the Pertagen® and Boostrix® groups.
Serious adverse events or reactions are defined as any untoward medical occurrence or effect that, at any dose: results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing inpatient’s hospitalisation, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect in the offspring of study subject and/or is medically significant (regardless of the cause).
Serious adverse events will be recorded by the participant in the unsolicited adverse event section of the diary card (ie day 0 to day 27) and also verified via interview with the study staff during visit 1 (day of randomisation and vaccination) and visit 2 (day 28 post-vaccination).
Timepoint [6] 371401 0
Day 28 post-vaccination.
Secondary outcome [7] 371402 0
Percentages of subjects with any reported serious adverse event (related or unrelated) from day 28 post-vaccination until 6 months post-vaccination in the Pertagen® and Boostrix® groups.
Serious adverse events or reactions are defined as any untoward medical occurrence or effect that, at any dose: results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing inpatient’s hospitalisation, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect in the offspring of study subject and/or is medically significant (regardless of the cause).
Participants will be queried regarding the occurrence of any serious adverse events during the protocol specified telephone contacts between the study staff and the participant that are scheduled at approximately 4 months and 8 months post-vaccination.
Timepoint [7] 371402 0
Day 28 post-vaccination to 6 months post-vaccination.
Secondary outcome [8] 371403 0
Percentages of subjects with reported related serious adverse events from month 6 post-vaccination until 1 year post-vaccination in the Pertagen® and Boostrix® groups.
Serious adverse events or reactions are defined as any untoward medical occurrence or effect that, at any dose: results in death, is life-threatening, requires inpatient hospitalisation or prolongation of existing inpatient’s hospitalisation, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect in the offspring of study subject and/or is medically significant (regardless of the cause).
Participants will be queried regarding the occurrence of any serious adverse events during the protocol specified telephone contacts at approximately 8 months post-vaccination and also during study visit 3 (approximately 1 year post-vaccination).
Timepoint [8] 371403 0
Month 6 post-vaccination until 1 year post-vaccination.

Eligibility
Key inclusion criteria
1. Age 18 to less than 26 years old
2. Provided written informed consent
3. Proven history of having received as primary pertussis immunisations 3 doses of an aPchem-containing vaccine in the first year of life or at least as a first dose wP containing vaccine.
4. Generally healthy as established by medical history and physical examination
5. Capable to comply with the study protocol
6. Negative urine pregnancy test for all females of child-bearing potential only (i.e. only females who have undergone sterilisation, hysterectomy or who are post-menopausal will not have a urine pregnancy test performed) and use of either a reliable method of contraception or abstinence during the first 2 months post-study vaccination.
Minimum age
18 Years
Maximum age
25 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1 History of significant medical illness such as immune deficiency, uncontrolled diabetes or hypertension heart or renal or hepatic diseases
2 Pregnant or breast-feeding women
3 History of allergy to any vaccine component
4 History of serious adverse event or neurological adverse event after injection with any vaccine
5 Having received any other vaccines within 28 days prior to recruitment (3 months for live attenuated vaccines)
6 Plan to receive any other vaccines within 28 days after study-related Pertagen®/Boostrix® vaccination
7 Plan to participate in another clinical trial of an investigational product during the study period (one year)
8 History of receiving blood or blood component or immunoglobulin within 3 months prior to recruitment
9 History of receiving immunosuppressive drugs or systemic corticosteroid (>0.5 mg/kg of prednisolone or equivalent for more than 14 days) within 3 months prior to recruitment
10 Having received pertussis vaccine within 5 years prior to recruitment
11 Having had whooping cough diagnosis or confirmed pertussis infection within 5 years prior to recruitment
12 Presence of acute febrile illness on the day of vaccination (This is a temporary exclusion criterion)
13 Any progressive or severe neurological disorder, seizure disorder or Guillain-Barré syndrome
14 Behavioural or cognitive impairment or psychiatric disease that in the opinion of the investigator may interfere with the subject's ability to participate in the study
15 History of alcoholism and/or clinically significant drug abuse
16 Presence of bleeding disorders, and abnormalities of splenic and thymic functions
17 Individuals with history of any illness that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subjects due to participation in the study

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 computer-generated randomisation list containing subject numbers and vaccine group assignments will be prepared by an independent Data Management Department. Copies of the randomisation list will be held in sealed envelopes by the Data Management Department. A copy will be made available to the study sites Clinical Trials Pharmacists who will be responsible for preparing and dispensing the study vaccines.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Subjects will be stratified according to whole-cell pertussis or acellular pertussis vaccination in infancy.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety
Statistical methods / analysis
Sample size calculation:
The sample size was calculated based on non-inferiority test with alpha level of 0.05 and 80% power, assuming seroconversion rate in the comparator (Boostrix® ) group was 86%. The sample size required for the study is 140 (Pertagen®) versus 70 (Boostrix®).

Analysis of demographics and baseline characteristics:
Demographic characteristics (age, ethnicity, sex) will be tabulated by vaccine group on the ITT data set. If more than 10% of the ITT data set is excluded from the PP data set, the description and comparability of vaccine groups at baseline will be repeated on the PP data set. Quantitative demographic variables, such as age, height, and weight, will be described as number of subjects, mean, standard deviation, minimum, median, maximum, and range. Qualitative demographic variables, such as ethnicity and sex, will be described by number of subjects and percentage for each vaccine group. Group comparison will be performed to confirm whether the vaccine groups are similar for demographic characteristics. Concomitant diseases at the first visit will be tabulated by vaccine group using the latest MedDRA dictionary code version. Any baseline variable with a random imbalance between vaccine groups that may have any influence on safety results (i.e. age) will be considered as covariate in the secondary analysis of the primary safety criteria.

Analysis of Reactogenicity:
The primary analysis objectives are to assess and compare reactogenicity of Pertagen® and Boostrix® vaccination. Primary analyses will reactogenicity from Day 0 to Day 7 based on solicited adverse events.

Analysis of Overall Safety:
The safety analysis will include all randomised subjects who have received a dose of Pertagen® or Boostrix®. The overall percentage of subjects with at least one spontaneously reported adverse event, with date of onset up to 28 days after vaccination, will be tabulated with exact 95% confidence intervals, by type of adverse event; by severity; and by causality. These events will be summarized and classified by System Organ Class and preferred term MedDRA. They will be displayed by vaccine group as both frequencies and percentages on the ITT data set. All reported adverse events that start post-vaccination will be tabulated. If a given disease is already reported as ongoing at the first visit on the medical history pages, it will be counted and tabulated as a vaccine emergent adverse event only if it worsens after the immunisation with the study vaccine.
Serious adverse events and discontinuation due to adverse event(s) will be described in detail by vaccine group.

Analysis of Immunogenicity:
The primary immunogenicity endpoint (non-inferiority of Pertagen® as compared to Boostrix®) is seroconversion rates as defined by percentage of subjects with a greater than or equal to 4-fold increase of IgG antibodies to PT and FHA at Day 28 with respect to baseline (Day 0; before vaccination). The following descriptive statistics may be provided for each variable: number of subjects, percentages, mean, geometric mean, standard deviation, median, minimum, maximum, and range.


Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA

Funding & Sponsors
Funding source category [1] 303011 0
Commercial sector/Industry
Name [1] 303011 0
Technovalia
Address [1] 303011 0
Eastern Innovation Business Centre
5a Hartnett Close
Mulgrave VIC 3170

Country [1] 303011 0
Australia
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
Perth Childrens’ Hospital
15 Hospital Avenue
Nedlands WA 6009
Australia
Country
Australia
Secondary sponsor category [1] 302983 0
None
Name [1] 302983 0
Address [1] 302983 0
Country [1] 302983 0
Other collaborator category [1] 280735 0
Commercial sector/Industry
Name [1] 280735 0
BioNet-Asia Co., Ltd.
Address [1] 280735 0
19 Soi Udomsuk 37, Sukhumvit 103 Road
Bangkok 10269,
Country [1] 280735 0
Thailand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 303562 0
Sir Charles Gairdner and Osborne Park Health Care Group HREC
Ethics committee address [1] 303562 0
2nd Floor A Block, Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS Western Australia 6009
Ethics committee country [1] 303562 0
Australia
Date submitted for ethics approval [1] 303562 0
17/04/2019
Approval date [1] 303562 0
04/07/2019
Ethics approval number [1] 303562 0

Summary
Brief summary
This study will be investigating the use of a new whooping cough vaccine in adults aged 18 - 25 years. Pertussis infection rates within this age group have been rising since the early 2000s and this is likely due to the short-term protection offered by the current pertussis booster vaccine. The study will compare the use of this new vaccine to the vaccine currently used in Australia. Randomisation will be based on the pertussis vaccination history of each particular subject and all subjects will be followed up for one year. They will have blood sampled before vaccination, at 28 days following vaccination and 1 year after vaccination. The expected outcome is that the new pertussis vaccine will demonstrate superior immune response and therefore extended protection against pertussis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 94094 0
A/Prof Peter Richmond
Address 94094 0
Telethon Kids Institute
Perth Childrens’ Hospital
15 Hospital Avenue
Nedlands WA 6009
Country 94094 0
Australia
Phone 94094 0
+61 8 6456 5699
Fax 94094 0
Email 94094 0
peter.richmond@uwa.edu.au
Contact person for public queries
Name 94095 0
Dr Tanya Stoney
Address 94095 0
Telethon Kids Institute
Perth Childrens’ Hospital
15 Hospital Avenue
Nedlands WA 6009
Country 94095 0
Australia
Phone 94095 0
+61 8 6319 1859
Fax 94095 0
Email 94095 0
Tanya.Stoney@telethonkids.org.au
Contact person for scientific queries
Name 94096 0
Dr Anita van den Biggelaar
Address 94096 0
Technovalia
Eastern Innovation Business Centre
5a Hartnett Close
Mulgrave VIC 3170
Country 94096 0
Australia
Phone 94096 0
+61 8 6319 1281
Fax 94096 0
Email 94096 0
anitavdb@technovalia.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
No Results