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Trial registered on ANZCTR


Registration number
ACTRN12618002041235
Ethics application status
Approved
Date submitted
11/12/2018
Date registered
20/12/2018
Date last updated
11/06/2019
Date data sharing statement initially provided
20/12/2018
Date results information initially provided
11/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Follow-up study to determine the safety, maximum tolerable dose and ability to provoke an immune response of the Codavax intranasal Influenza Vaccine in healthy adult volunteers..
Scientific title
A Randomized Double-Blind, Placebo Controlled, Phase I Study of the Safety, Tolerability, and Immunogenicity of a Live Attenuated H1N1 Vaccine in Healthy Individuals
Secondary ID [1] 296750 0
CODA01-002
Universal Trial Number (UTN)
U1111-1224-7771
Trial acronym
Linked study record
This is a follow-up study to CODA01-001 (ACTRN12617000254392 and ACTRN12618000557235)

Health condition
Health condition(s) or problem(s) studied:
Influenza 310630 0
Condition category
Condition code
Infection 309350 309350 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A randomized, double-blind, placebo controlled, Phase I study with 33 sero-susceptible individuals aged 18 to 45 years.

A total of 33 healthy individuals will be enrolled and randomized into 2 groups where each participant will receive a single dose of either CodaVax-H1N1, or placebo (22:11). Participants will receive one 0.1ml into both nostrils (one immediately after the other).

Twenty-two (22) participants will be administered CodaVax-H1N1 and 11 participants will be administered a placebo. All subjects will receive an intranasal (IN) dose of either CodaVax-H1N1, or saline (placebo).

Arm 1: Intranasal dose of CodaVax-H1N1
Arm 2: Intranasal dose of Placebo (Saline)

CodaVax-H1N1 is a potential universal live attenuated influenza vaccine (LAIV) manufactured using a proprietary SAVE platform based on the H1N1 A/California/07/2009 (H1N1) strain. The vaccination dose will be 8 x 10^5 PFU in 200 microlitre of current Good Manufacturing Practice (cGMP) Dulbecco Modified Eagle Medium media and 7.5% sucrose, and is to be administered through an intranasal sprayer into one or both nostrils.

As the CodaVax-H1N1 dose is 8-times higher than the highest dose administered in the first clinical trial (UTN: U1111-1191-3515), the first 3 participants dosed with CodaVax-H1N1 will be sentinel participants. These participants will be monitored for 60 to 90 minutes immediately following dosing on Day 0 (visit 3), and return for testing on Day 2 (visit 3) and Day 6 (visit 4). If dosing of the sentinels proceeds without clinically significant adverse events (AEs) over 7 days, all remaining participants will be dosed.

Following vaccination all participants (CodaVax, and placebo) will be monitored at the clinic for at least 60-90 minutes following vaccination, after which they will return to the clinic (Day 2 and 6) to be monitored until Day 6 post-vaccination and on Day 30 post-vaccination for a Follow-up visit.

A soft-lock will be placed on the database after the Day 30 Follow-up visits are complete, at which point the data will be unblinded and an interim preliminary report will be written.

All participants will then receive an open-label Close-out phone interview 6 months post-vaccination and a final clinical study report will be written.
Intervention code [1] 313063 0
Treatment: Other
Comparator / control treatment
The placebo arm is 0.9% saline given as a 0.lmL dose per nostril on Day 0.
Control group
Placebo

Outcomes
Primary outcome [1] 308304 0
The primary outcome of this study is the assessment of the safety profile and tolerability of CodaVax-H1N1 influenza vaccine compared to placebo controls when administered to healthy adults. This is a composite primary outcome and will be tested by clinical laboratory testing, physical examination, vital sign assessments, noting the frequency and types of adverse events. The expected adverse events related to influenza vaccines are runny nose, nasal congestion, sore throat, chills, loss of appetite, shivers, fatigue, headache, sweating, muscle pain, vomiting, diarrhoea, chest pain, shortness of breath, joint pain. The participant will be asked to record these on a diary for 6 days after the day of dosing and the site staff will also specifically query for these at each visit
Timepoint [1] 308304 0
daily for 6 days post vaccination, at site visit on day 30 and as part of the 6 month follow-up phone call.
Secondary outcome [1] 354582 0
Geometric mean titres (GMT) of anti-A/Michigan/45/2015 (H1N1) antibodies (HAI) at Day 0 and Day 30, for each treatment arm. This will be assessed by blood serum assay.
Timepoint [1] 354582 0
At Day 0 and Day 30 after vaccination.
Secondary outcome [2] 354583 0
Geometric mean fold increase (GMFI) of anti-A/Michigan/45/2015 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline, for each treatment arm
Timepoint [2] 354583 0
At Day 30 after vaccination.
Secondary outcome [3] 354584 0
The percentage of participants, regardless of sero-status, within each treatment arm who experience an H1N1 MI/45/2015 specific sero-response post dose between Day 0 and Day 28 to 35. Sero-response is defined as a equals 4-fold rise in HAI titre from baseline. This will be assessed by blood serum assay at day 6 and day 30 as compared to the blood serum assay at baseline (day 0 pre-dose).
Timepoint [3] 354584 0
At Day 0 and Day 28-35 after vaccination.
Secondary outcome [4] 354585 0
The percentage of sero-susceptible participants within each treatment arm who experience an H1N1 MI/45/2015 specific sero-response post dose between Day 0 and Day 28 to 35. Sero-response is defined as a equals 4-fold rise in HAI titre from baseline. Participants with a baseline HAI titre <10 (MI/45/2015) will be considered to be sero-susceptible for H1N1.
This will be assessed by blood serum assay at day 6 and day 30 as compared to the blood serum assay at baseline (day 0 pre-dose).
Timepoint [4] 354585 0
At Day 0 and Day 28-35 after vaccination.
Secondary outcome [5] 354586 0
The percentage of participants within each treatment arm with a equals 2-fold rise in serum IgG antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0
Timepoint [5] 354586 0
At Day 30 after vaccination.
Secondary outcome [6] 354587 0
GMFI within each treatment arm in serum IgG antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0
Timepoint [6] 354587 0
At Day 30 after vaccination.
Secondary outcome [7] 354588 0
The percentage of participants within each treatment arm with a equals 2-fold rise in serum IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0
Timepoint [7] 354588 0
At Day 30 after vaccination.
Secondary outcome [8] 354589 0
GMFI within each treatment arm in serum IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 30 compared to Day 0
Timepoint [8] 354589 0
At Day 30 after vaccination.
Secondary outcome [9] 354590 0
The percentage of participants within each treatment arm with a equals 2-fold rise in salivary IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 6 and Day 30 compared to Day 0
Timepoint [9] 354590 0
At Day 6 and Day 30 after vaccination.
Secondary outcome [10] 354591 0
GMFI within each treatment arm in salivary IgA antibody responses to whole virus MI/45/2015 by ELISA on Day 6 and Day 30 compared to Day 0
Timepoint [10] 354591 0
At Day 6 and Day 30 after vaccination.

Eligibility
Key inclusion criteria
1. Adult volunteers, aged 18 to 45 years (at the time of screening).
a. In good general health in the opinion of the Medical Investigator or delegate, with no significant medical history and no clinically significant abnormal findings at screening. Participants with minor medical problems (for example, mild gastro-oesophageal reflux), which are unlikely to interfere with participant safety, the study procedures and/or results, and are not excluded elsewhere in the protocol, may be included at the discretion of the Medical Investigator. Furthermore, medications which are unlikely to interfere with participant safety, study procedures and/or results, and which are not excluded elsewhere in the protocol, may be permitted at the discretion of the Medical Investigator.
2. Participants must use highly effective, double contraception from the Screening Visit and up to the Follow-up Visit (Day 30). Double 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
d. Documented evidence of surgical sterilization 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;
Males must not donate sperm for at least 70 days 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 Day 30. WNOCBP must be post-menopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by FSH level meets the requirement of post-menopausal women if in doubt.
Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not considered highly effective methods of birth control. Participant abstinence for the duration of the study and 1 month after the last study treatment is acceptable.
3. Must be willing to comply with the following conditions to prevent the spread of GMOs according the Office of Gene Technology Regulator (OGTR) Licence (DIR 144):
a. Hygiene measures intended to prevent interpersonal transmission of study drug must be implemented, including but not limited to frequent handwashing with soap or hand disinfectant, respiratory hygiene and cough etiquette within 7 days following vaccination
b. Blood, tissue or organs must not be donated within 7 days of vaccination
c. Severely immunosuppressed persons who require a protective environment are not to be cared for by the participant within 7 days of vaccination
d. Contact is not to be made with severely immunosuppressed persons who require a protective environment within 7 days of vaccination
e. All tissues and materials used to collect respiratory secretions are to be sealed in a primary container and placed within a secondary container so that it is not accessible to children or animals for 7 days until it is returned to the study site for disposal, for 7 days within vaccination
4. Contact is not to be made with infants <6 months of age within 7 days of vaccination
5. Adequate venous access in the left or right arms to allow collection of a number of blood samples
6. Must be Sero-susceptible <10 HAI titre MI/45/2015 Influenza virus (pre-screen)
7. Laboratory Testing:
a. Full blood examination and biochemistry within the laboratory defined normal range unless deemed not clinically significant by the investigator, however a small drop below the normal range for Absolute Neutrophil Count (ANC) may be acceptable as per investigator discretion;
b. Urinalysis: Negative urine glucose, negative or trace urine protein, negative or trace urine HgB (if trace HgB is present on dipstick, a microscopic urinalysis within institutional range);
8. Able to communicate effectively with study personnel and considered reliable, willing and cooperative in terms of compliance with the protocol requirements
9. Participant does not intend to start or change an existing physical conditioning regimen prior to or during the study period
10. Participant has voluntarily given written informed consent to participate in the study (prior study entry)
11. Participant is available for the duration of the study
Minimum age
18 Years
Maximum age
45 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Immunodeficiency (including HIV) or autoimmune disorder, or participant is currently taking drugs (excluding steroids, see exclusion criteria 16) or was undergoing a form of treatment within 3 months prior to study entry that affects the immune system, or participant is living with somebody with the same.
2. Participant is not to have had Guillain-Barre Syndrome
3. Received blood or blood products in the 3 months prior to screening
4. Received another vaccine within 30 days before screening
5. Received another influenza vaccine from 2016 to present year
6. Participants with plans to travel to the Northern Hemisphere during the Screening period
7. Participated in another clinical study (involving an investigational product or device) within 60 days before screening
8. Suffered previous anaphylactic reaction to foods, vaccines, drugs or hymenoptera stings, or has a history of severe allergic reactions (e.g. clinically severe urticaria, asthma)
9. Participants with active asthma, or a history of childhood asthma which was treated with corticosteroids.
10. Participants with a known egg allergy
11. If female, pregnant, planning to become pregnant, or lactating, or participants is living with somebody who is pregnant or lactating
12. 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 > 4 standard drinks (or equivalent) per day
13. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study
14. Current or history of significant neurological, cardiovascular, pulmonary (including asthma), hepatic, rheumatic, autoimmune, hematological, metabolic or renal disorder
15. Clinically significant abnormal laboratory value at screening as determined by the Investigator
16. Known or suspected impairment/alteration of immune function, including: Chronic use of oral steroids (equivalent to 20 mg/day prednisone equals 12 weeks /equals 2 mg/kg body weight / day prednisone equals 2 weeks) within 60 days prior to Day 0 (use of inhaled, IN, or topical corticosteroids is allowed, unless used for the management of asthma – see exclusion criteria 9). Receipt of parenteral steroids (equivalent to 20 mg/day prednisone equals 12 weeks /equals 2 mg/kg body weight/day prednisone equals 2 weeks) within 60 days prior to Day 0. Or participant is living with somebody with the same.
17. Unusual dietary habits and excessive or unusual vitamin intake likely, in the opinion of the Investigator, to affect safety parameters
18. Participant is seropositive to HCV or HBV
19. Body temperature (oral) equals 38.0 degrees Celsius or acute illness within 5 days prior to vaccination
20. 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
21. 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 administering 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/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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)
QLD,VIC
Recruitment hospital [1] 12612 0
Nucleus Network - Melbourne
Recruitment hospital [2] 13514 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 25030 0
3004 - Melbourne
Recruitment postcode(s) [2] 26133 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 301330 0
Commercial sector/Industry
Name [1] 301330 0
Codagenix Australia Pty Ltd
Address [1] 301330 0
Level 1, 1805 Gold Coast Highway, Burleigh Heads, Queensland, 4220
Country [1] 301330 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Clincial Network Services (CNS) Pty Ltd
Address
Level 2, 381 MacArthur Ave, Hamilton QLD 4007, Australia
Country
Australia
Secondary sponsor category [1] 300995 0
Commercial sector/Industry
Name [1] 300995 0
Codagenix Australia Pty Ltd
Address [1] 300995 0
Level 1, 1805 Gold Coast Highway, Burleigh Heads, Queensland, 4220
Country [1] 300995 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302070 0
Bellberry Limited
Ethics committee address [1] 302070 0
129 Glen Osmond Road, Eastwood, South Australia, 5063
Ethics committee country [1] 302070 0
Australia
Date submitted for ethics approval [1] 302070 0
31/10/2018
Approval date [1] 302070 0
12/12/2018
Ethics approval number [1] 302070 0
2018-10-914

Summary
Brief summary
CodaVax-H1N1, the study drug being researched in this project, is an experimental vaccine being developed by Codagenix, Inc. This means that it is not an approved treatment in Australia, and is not yet approved anywhere else in the world.

CodaVax-H1N1 is a vaccine that is intended to prevent influenza.

The primary objective of this study is to determine the safety and tolerability of CodaVax-H1N1 influenza vaccine compared to placebo control when administered to healthy adults.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 89018 0
Dr Ben Snyder
Address 89018 0
5th Floor, Burnet Tower, Alfred Medical Research and Education (AMREP) Precinct
89 Commercial Road, Melbourne, VIC 3004.
Country 89018 0
Australia
Phone 89018 0
+61 3 8593 9838
Fax 89018 0
Email 89018 0
b.snyder@nucleusnetwork.com.au
Contact person for public queries
Name 89019 0
Dr J. Robert Coleman
Address 89019 0
Codagenix Inc.
3 Bioscience Park Drive
Farmingdale, NY 11735-0176
Country 89019 0
United States of America
Phone 89019 0
+1 516 448 5073
Fax 89019 0
Email 89019 0
info@codagenix.com
Contact person for scientific queries
Name 89020 0
Dr J. Robert Coleman
Address 89020 0
Codagenix Inc.
3 Bioscience Park Drive
Farmingdale, NY 11735-0176
Country 89020 0
United States of America
Phone 89020 0
+1 516 448 5073
Fax 89020 0
Email 89020 0
info@codagenix.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data sharing statement was marked 'No' with the reason being that this is a healthy volunteer study and the individual participant results are not useful to the participants or to others outside of the Sponsor.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary