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Trial registered on ANZCTR


Registration number
ACTRN12617001027303
Ethics application status
Approved
Date submitted
13/07/2017
Date registered
17/07/2017
Date last updated
5/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study to determine the safety, tolerability and ability to provoke an immune response of graded doses of the STX-100/Alhydrogel vaccine in healthy volunteers
Scientific title
Randomised, Double-Blind, Controlled Phase I Trial of the Safety, Tolerability and Immunogenicity of Graded Doses of STX-100/Alhydrogel, a Recombinant Enterovirus A 71 (EV-A71) Virus-Like Particle Vaccine in Healthy Adults
Secondary ID [1] 291844 0
Nil known
Universal Trial Number (UTN)
U1111-1196-2054
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hand, foot and mouth disease 303093 0
Condition category
Condition code
Infection 302552 302552 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A First-in-Human, Randomised, Double-Blind, Controlled, Dose-Ranging, Phase 1 Study in Healthy Volunteers aged 18 to 39 years.
A total of 20 healthy male and female participants will receive two intramuscular doses of STX-100/Alhydrogel vaccine (dose level 4.6 mcg, and 18.4 mcg) or control (Placebo EV71VLP/Alhydrogel which is Bis-Tris sterile buffer solution, 150 mM NaCl, at pH 6.5 mixed with aluminium hydroxide) at Day 1 and Day 28.
Participants will be recruited in two sequential dosing groups:
Cohort 1: 8 participants will receive 4.6mcg STX-100/Alhydrogel vaccine and 2 participants will receive placebo
Cohort 2: 8 participants will receive 18.4mcg STX-100/Alhydrogel vaccine and 2 participants will receive placebo

The investigational study vaccine, the STX-100/Alhydrogel vaccine will consist of two fractions: one, the liquid fraction containing the recombinant EV-A71 VLP (labeled “EV71 VLP DP”), and two, the adjuvant, aluminium hydroxide, Al(OH)3 (diluted Alhydrogel). The recombinant EV-A71 VLP will be absorbed to the adjuvant to prepare the finished product for injection.
The study control will be a Placebo, comprising of the Placebo product mixed with the adjuvant Aluminium Hydroxide (Placebo EV71 VLP/Alhydrogel).

As this is a first-in-human study, 2 sentinel participants (1 placebo and 1 STX-100/Alhydrogel vaccine) in each cohort, will receive the first dose and be monitored for 24hrs. If dosing of the sentinels proceeds with no clinically significant adverse events, the remaining participants will be dosed.

Following the first vaccination, all participants will be monitored at the clinic for at least 60-90 minutes, after which they will return to the clinic on day 7 and day 28 to be monitored. At day 28, the 2nd vaccination will be given and participants will be monitored at the clinic for 60-90 minutes. Participants will return to the clinic at day 7 and 28 after the 2nd vaccination (study day 35 and 56) for monitoring.

A soft-lock will be placed on the database after the Day 56 visit at which point the data will be unblinded and an interim preliminary report will be written.

All participants will attend the clinic at 3 months and 6 months post-vaccination for follow-up visits (open-label).
Intervention code [1] 297962 0
Treatment: Drugs
Comparator / control treatment
The placebo group consists of IM injection of Bis-Tris sterile buffer solution, 150 mM NaCl, at pH 6.5 mixed with the adjuvant, diluted Alhydrogel
Control group
Placebo

Outcomes
Primary outcome [1] 301985 0
The primary outcome of this study is the assessment of the safety and tolerability of the STX-100/Alhydrogel vaccine, administered at 2 dose levels in healthy adults, compared to the placebo. This will be tested by clinical laboratory testing, physical examination, vital signs assessments, noting the frequency and types of AE and the use of concomitant medication
Timepoint [1] 301985 0
Daily for 7 days post vaccination
Secondary outcome [1] 334444 0
The Secondary outcome of this study is the assessment of the immunogenicity of STX-100/Alhydrogel vaccine administered at 2 dose levels in healthy adults, compared to placebo. Immunogenicity will be assessed by analysis of serum samples collected at visit 1, 4,7,8 and 9; testing for the presence of EV-A71 antibodies.
Timepoint [1] 334444 0
Day 1, day 28, day 56, 3 months and 6 months after first vaccination

Eligibility
Key inclusion criteria
1. Adult volunteers, aged 18–39 years (at the time of Screening).
2. Seronegative (PRNT50 less than1:20) or low level antibodies (PRNT50 less than or equal to 1:40) for neutralising antibodies to EV-A71.
3. In general good health, in the opinion of the Investigator, with no significant medical history or abnormal findings at Screening. Particular attention will be paid to:
a) A drug history identifying any known drug allergies and the presence of drug abuse.
b) Any chronic use of medication(s); and
c) Thorough review of body systems.
4. WOCBP must use highly effective, double barrier contraception for at least one month prior to Visit 1 (first vaccination) and up to Visit 7 (28 days after second vaccination; i.e. during Part A). Double barrier contraception is defined as a condom AND one other form of the following:
a) Established hormonal contraception (with approved oral, injected or depot regimen) for at least 2 months prior to Screening.
b) Depot or injectable birth control.
c) Intrauterine device or intrauterine system in place for at least 2 months prior to Screening.
Documented evidence of surgical sterilisation at least 6 months prior to Screening visit. i.e., tubal ligation or hysterectomy for women or vasectomy for men (with appropriate post-vasectomy documentation of the absence of sperm in semen) provided the male partner is a sole partner.
5. Males must not donate sperm for at least 1-month post-dose of the last study treatment. Male partners of female participants and female partners of male participants must also use contraception, if they are of childbearing potential. WOCBP must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day 1, Day 28. Women not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle stimulating hormone (FSH) level more than 40 mIU/mL if in doubt.
6. Rhythm methods will not be considered as highly effective methods of birth control. Participant abstinence for the duration of the study and 1 month after the last study treatment is acceptable.
7. Adequate venous access in their left or right arms to allow collection of a number of blood samples.
8. No birthmarks, tattoos, wounds or other skin conditions on both forearms which could reasonably obscure injection site reactions.
9. Able to communicate effectively with study personnel and is considered reliable, willing and cooperative in terms of compliance with the protocol requirements.
10. Participant does not intend to start or change an existing physical conditioning regimen prior to or during the treatment period (Part A).
11. Have voluntarily given written informed consent to participate in the study (prior study entry).
12. Participant is available for the duration of the study.
Minimum age
18 Years
Maximum age
39 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Immunodeficiency or autoimmune disorder, or is currently taking drugs or was undergoing a form of treatment within 6 weeks prior to Screening that affects the immune system. (Treatment of asthma with low dose corticosteroids equivalent to prednisone less than 10 mg per day, is permitted).
2. Received blood or blood products in the 3 months’ days prior to Screening.
3. Received another vaccine within 30 days before Screening and/or received any other vaccine during Part A of the study (until Visit 7, 28 days after second vaccination).
4. Participates in another clinical trial (involving an investigational product or device) within 60 days before Screening or during Part A of the study (until Visit 7, 28 days after second vaccination).
5. No donation of blood, blood fractions and plasma within 30 days before the first vaccination until 4 weeks after the second vaccination (Day 56, i.e. Visit 7).
6. Suffered previous anaphylactic reaction to foods, vaccines, drugs or hymenoptera stings, or has a history of severe allergic reactions (e.g. clinically severe urticaria).
7. If female is pregnant, planning to become pregnant, or lactating.
8. Participant is seropositive for neutralising antibodies to EV-A71 (PRNT50 more than 1:40).
9. Participant has a history of, or current evidence at the time of Screening of abuse of alcohol or any drug substance, licit or illicit, or current alcohol consumption is more than 4 standard drinks (or equivalent) per day.
10. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study.
11. Current or history of significant neurological, cardiovascular, pulmonary, hepatic, rheumatic, autoimmune, haematological, metabolic or renal disorder.
12. Clinically significant abnormal laboratory value at Screening as determined by the Investigator.
13. Unusual dietary habits and excessive or unusual vitamin intake likely, in the opinion of the Investigator, to affect safety pathology parameters.
14. Participant is seropositive to HIV, HCV or HBsAg.
15. Body temperature (oral) more than or equal to 38.0ºC (100.4ºF) or acute illness within 3 days prior to vaccination (participant may be rescheduled to a later cohort).
16. Any skin marking, tattoo or blemish precluding injection site inspection.
17. Any other significant finding that, in the opinion of the Investigator, would increase the risk of the individual having an adverse outcome from participating in this study.
18. Participant is a member of the team or is related or in a dependent relationship with a member of the study team, as defined as the Sponsor or study site personnel.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
18/01/2018
Actual
18/01/2018
Date of last participant enrolment
Anticipated
1/02/2018
Actual
Date of last data collection
Anticipated
2/08/2018
Actual
Sample size
Target
20
Accrual to date
3
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9762 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 18540 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 296341 0
Commercial sector/Industry
Name [1] 296341 0
Sentinext Therapeutics Sdn Bhd
Country [1] 296341 0
Malaysia
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services (CNS) Pty Ltd
Address
Level 4, 88 Jephson Street
Toowong, Brisbane, QLD, 4066
Australia
Country
Australia
Secondary sponsor category [1] 295271 0
Commercial sector/Industry
Name [1] 295271 0
Sentinext Therapeutics Sdn Bhd
Address [1] 295271 0
Malaysian Technology Development Corporation Sdn Bhd
Ground Floor, Menara Yayasan Tun Razak Jalan Bukit Bintang,
55100 Kuala Lumpur
Country [1] 295271 0
Malaysia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297572 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 297572 0
Ethics committee country [1] 297572 0
Australia
Date submitted for ethics approval [1] 297572 0
18/10/2017
Approval date [1] 297572 0
21/11/2017
Ethics approval number [1] 297572 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74482 0
Dr Jason Lickliter
Address 74482 0
Nucleus Network Ltd, 5th Floor, Burnet Tower, AMREP Precinct, 89 Commercial Road, Prahran 3004
Country 74482 0
Australia
Phone 74482 0
+61 3 9076 8906
Fax 74482 0
Email 74482 0
J.Lickliter@nucleusnetwork.com.au
Contact person for public queries
Name 74483 0
Zarifah Reed
Address 74483 0
Sentinext Therapeutics Sdn Bhd
Suite 19H, Level 19 Menara Northam
55 Jalan Sultan Ahmad Shah
10050 Penang, Malaysia
Country 74483 0
Malaysia
Phone 74483 0
+33 695695786
Fax 74483 0
Email 74483 0
za@tulasiconsult.com
Contact person for scientific queries
Name 74484 0
Zarifah Reed
Address 74484 0
Sentinext Therapeutics Sdn Bhd
Suite 19H, Level 19 Menara Northam
55 Jalan Sultan Ahmad Shah
10050 Penang, Malaysia
Country 74484 0
Malaysia
Phone 74484 0
+33 695695786
Fax 74484 0
Email 74484 0
za@tulasiconsult.com

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIVirus-like particle vaccines: immunology and formulation for clinical translation2018https://doi.org/10.1080/14760584.2018.1516552
EmbasePlant Viruses and Bacteriophage-Based Reagents for Diagnosis and Therapy.2020https://dx.doi.org/10.1146/annurev-virology-010720-052252
N.B. These documents automatically identified may not have been verified by the study sponsor.