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Trial registered on ANZCTR


Registration number
ACTRN12613000030774
Ethics application status
Approved
Date submitted
9/01/2013
Date registered
11/01/2013
Date last updated
28/01/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
A Randomized, Double Blinded Within Dose, Controlled, Safety and Immunogenicity Study of Group A Streptococcus Vaccine Candidate in Healthy Participants
Scientific title
A Randomized, Double Blinded Within Dose, Controlled, Safety and Immunogenicity Study of Group A Streptococcus Vaccine Candidate in Healthy Participants
Secondary ID [1] 281710 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Group A Streptococcus (GAS) infection 288010 0
Condition category
Condition code
Infection 288385 288385 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The vaccine candidate is a synthesized peptide antigen from the conserved region of the M-protein (Peptide AcJ8) conjugated to Diphtheria Toxoid (D) as a carrier protein mixed with alum (Alhydrogel, 2% Aluminum hydroxide) adjuvant. The vaccine candidate will be formulated to contain 50microgram of the peptide conjugate (15 microgram of AcJ8 and 35 microgram of D). It will be administrated intramuscularly (i.m.) in a total volume of 0.5mL of phosphate buffered saline.Participants will be randomized in a 3:1 ratio to receive either two injections each containing 50 microgram of the vaccine candidate or two injections of saline at eight-week intervals.
Intervention code [1] 286249 0
Treatment: Drugs
Comparator / control treatment
Participants will be randomized in a 3:1 ratio to receive either two injections each containing 50 microgram of the vaccine candidate or two injections of saline at eight-week intervals. 2 participants will be dosed, 1 placebo and 1 investigational product 24 hours before the remaining 18 participants.
Control group
Placebo

Outcomes
Primary outcome [1] 288557 0
To evaluate the safety of Group A Streptococcus vaccine candidate when delivered intramuscularly to healthy adults in two doses of 50microgram AcJ8-D adsorbed onto alum.
Safety of the vaccine candidate will be assessed on the basis of the frequency and occurrence of injection site and systemic reactions following administration of the investigational vaccine. Safety parameters that will be monitored include changes in clinical biochemistry and haematology values on blood and urine, and changes in electrocardiogram and transthoracic echocardiograms.
Timepoint [1] 288557 0
Four weeks post each study product administration and then at 6,9 an 12 months after the initiation of the study.
Secondary outcome [1] 300463 0
To assess the immunogenicity of a Group A streptococcus vaccine candidate delivered intramuscularly to healthy adults in two doses of 50 microgram AcJ8-D adsorbed onto alum
The immune response to the AcJ8-1666 D vaccine will be assessed by:
1.Monitoring for the presence of vaccine-specific antibodies in all participants of the study and the titer of the vaccine-specific antibodies after each administered dose of the vaccine candidate, to investigate the relationship between the doses administered and the titer of vaccine-specific antibodies. 2.Measuring the bactericidal activity of the induced antibodies against different standard reference strains of Group A Streptococcus such as M1, M6, and 88/30.
Timepoint [1] 300463 0
Four weeks post each study product administration and then at 6,9 an 12 months after the initiation of the study.

Eligibility
Key inclusion criteria
1. Able to understand the purpose and the procedures involved in this study and sign the informed consent form;
2.Male or non-pregnant female adults, 18-45 years of age inclusive;
3.Non smokers and in good general health, as determined by screening evaluation, no greater than 28 days before the first dose in the form of medical history, clinical laboratory tests and physical examination;
4. Normal Electrocardiogram (ECG);
5.Echocardiogram (ECHO) that is normal or with findings that are considered trivial and clinically insignificant such as: 'Clinically insignificant/trivial mitral regurgitation (E 662 ROA of <10mm2,) ;
6.Women must agree not to become pregnant for the first 180 days of the trial. If they are sexually active, they must use an effective method of birth control, e.g. insertable, injectable, transdermal, or combination oral contraceptive approved by the US FDA or TGA combined with a barrier contraceptive and have negative results on a serum or urine pregnancy test done before administration of study medication;
7.Intention to reside in the geographical area for next 12 months and not intending to travel overseas for at least 30 days following the last study vaccine administration;
8. Agree not to participate in any other clinical trial during the trial;
9.Agree not to donate blood for the first 180 days of the trial;
10.Agree to restrain from intensive physical exercise i.e. exercise that varies significantly from an every day exercise routine, 3 days before and after (+/-3 days) administration of each dose, including each interim visit for blood sample collection.
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1.Personal or family history of post-streptococcal disease (rheumatic fever or glomerulonephritis), or collagen-vascular disease;
2.Evidence of increased cardiovascular disease risk;
3. Previous use of phentermine (appetite suppressant of the amphetamine and phenethylamine class), fenfluramine or dexfenfluramine known as Fen-Phen, anti-obesity medications (possible association with cardiac valvular abnormalities)
4.Clinical diagnosis or evidence of recent group A streptococcal infection;
5.Positive group A streptococcus throat culture at screening visit or positive rapid antigen test result on day of study product administration;
6.Presence of significant acute infections requiring systemic antibiotic treatment within the 14 days prior to each product administration;
7.Pregnant or breast feeding (all women will have a negative pregnancy test result prior to each study product administered;
8.Immunized or intent to immunize with any vaccine or investigational agents within 30 days prior to enrollment through to 30 days following the last study vaccine administration, with the exception of licensed inactivated influenza vaccines;
9.Receipt of diphtheria toxoid containing vaccine within the previous 5 years (such as DTP,Hepatitis A, Boostrix, Adacel or Menactra);
10.Past significant reaction following any previous vaccination;
11.History of hypersensitivity to any diphtheria toxoid containing vaccine;
12.Presence of acute infectious disease or fever;
13.Presence of current or suspected serious chronic diseases
14.Evidence and any history of leukaemia, lymphoma or neoplasm;
15. Presence or suspicion of impaired immune system function
16.Received blood, blood products or a parenteral immunoglobulin preparation in the past 12 weeks;
17.Evidence of bleeding diathesis or any condition that may be associated with a prolonged bleeding time;
18.Known inherited genetic anomaly (known as cytogenic disorders) e.g., Down’s syndrome;
19.Findings of definite, probable or possible rheumatic heart disease (RHD), definite or probable acute rheumatic fever (ARF)
20.Clinical significant abnormal laboratory results;
21.The participant has a diagnosis of schizophrenia, bi-polar disease, or other severe(disabling) chronic psychiatric diagnosis;
22.The participant has been hospitalized within the past 5 years prior to enrollment for psychiatric illness, history of suicide attempt or confinement for danger to self or others;
23.The participant is receiving psychiatric drugs. Participants who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study;
24.The participant has a history of alcohol or drug abuse in the 5 years prior to enrolment.


Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Two sentinel participants will be enrolled and randomly selected to receive either the investigational vaccine or the control saline 24 hours before all other participants. Assuming that no immediate serious adverse reactions are observed in these sentinel participants, the remaining 18 participants will be enrolled and dosed. The sentinel participants will receive their second dose at the same time as the remaining participants.
Enrolment will be conducted by Q-Pharm.The randomization code will be included in the enrolment module for the trial. The randomization code will link the vial allocation number to the treatment assignment. Each subject enrolled in the trial is assigned to a vial allocation number after demographic and eligibility data have been entered into the system. The code list for emergency unblinding purposes and will be kept in a secure place at the clinical site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomised sequence
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 1
Type of endpoint(s)
Safety
Statistical methods / analysis
The analysis will be primarily descriptive, and will include tabular and graphical summaries of the safety and immunogenicity data, supplemented by a complete listing of outcomes for each participant. The sample size chosen will not provide sufficient power to test for differences or similarities amongst the study product urine and recipients. Preference will be given to reporting point and confidence interval estimates, rather than p-values associated with formal hypothesis testing. All analyses will be regarded as exploratory, and any significant findings will be regarded as hypothesis generating, rather than
hypothesis confirming.


Recruitment
Recruitment status
Completed
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)
QLD
Recruitment postcode(s) [1] 6150 0
4006 - Herston

Funding & Sponsors
Funding source category [1] 286512 0
Government body
Name [1] 286512 0
National Institutes of Health (NIH),
Address [1] 286512 0
9000 Rockville Pike, Bethesda, Maryland 20892
Country [1] 286512 0
United States of America
Funding source category [2] 286522 0
Other
Name [2] 286522 0
The Lowija Institute
Address [2] 286522 0
179 Grattan Street, Carlton
VIC 3053
Country [2] 286522 0
Australia
Primary sponsor type
Other
Name
Queensland Institute of Medical Research
Address
300 Herston Road, Herston, QLD 4029
Country
Australia
Secondary sponsor category [1] 285301 0
None
Name [1] 285301 0
Address [1] 285301 0
Country [1] 285301 0
Other collaborator category [1] 277235 0
University
Name [1] 277235 0
Griffith University, Gold Coast campus
Address [1] 277235 0
Parklands Drive, Southport, QLD 4222
Country [1] 277235 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288587 0
Queensland Institute of Medical Research Human Research Ethics Committee (QIMR-HREC)
Ethics committee address [1] 288587 0
300 Herston Road, Herston, QLD 4029
Ethics committee country [1] 288587 0
Australia
Date submitted for ethics approval [1] 288587 0
05/11/2012
Approval date [1] 288587 0
07/12/2012
Ethics approval number [1] 288587 0
P1199

Summary
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of a Group A Streptococcus vaccine candidate. The participants (N=20) will be randomized 3:1 to receive the active intervention (N=15) or saline as placebo control (N=5).
Trial website
Trial related presentations / publications
none to date
Public notes

Contacts
Principal investigator
Name 36766 0
Dr James S. McCarthy
Address 36766 0
Queensland Institute of Medical Research
Infectious Diseases and Immunology
300 Herston Road, Herston 4006
Brisbane, Queensland,
Country 36766 0
Australia
Phone 36766 0
+61 7 3845 3796
Fax 36766 0
+61 7 3362 0104
Email 36766 0
James.McCarthy@qimr.edu.au
Contact person for public queries
Name 36767 0
Ms Silvana Sekuloski
Address 36767 0
Queensland Institute of Medical Research
300 Herston Road, Herston 4006
Brisbane, Queensland,
Country 36767 0
Australia
Phone 36767 0
+61 7 3845 3856
Fax 36767 0
+61 7 3345 3507
Email 36767 0
Silvana.Sekuloski@qimr.edu.au
Contact person for scientific queries
Name 36768 0
Dr James S. McCarthy
Address 36768 0
Queensland Institute of Medical Research
300 Herston Road, Herston 4006
Brisbane, Queensland,
Country 36768 0
Australia
Phone 36768 0
+61 7 3845 3796
Fax 36768 0
+61 7 3362 0104
Email 36768 0
James.McCarthy@qimr.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary