Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000557235
Ethics application status
Approved
Date submitted
5/04/2018
Date registered
13/04/2018
Date last updated
7/08/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study to determine the safety, maximum tolerable dose and ability to provoke an immune response of the Codavax Influenza Vaccine in healthy volunteers. Part 2
Scientific title
A Randomised, Double-Blind, Double-Dummy, Active and Placebo Controlled Phase 1 Study of the Safety, Tolerability and Immunogenicity of the Codavax Influenza Vaccine in healthy volunteers Part 2
Secondary ID [1] 294508 0
Nil known
Universal Trial Number (UTN)
U1111-1211-8420
Trial acronym
Linked study record
This study is a follow up study of the corresponding study with ANZCTR ID number ACTRN12617000254392. This study is part 2 of the linked study

Health condition
Health condition(s) or problem(s) studied:
Influenza 307279 0
Condition category
Condition code
Infection 306397 306397 0 0
Studies of infection and infectious agents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will comprise of 50 participants who will be randomised into 2 groups where each participant will receive a single dose of either CodaVax or placebo (40:10).

Forty (40 participants will be administered CodaVax and ten (10) participants will be administered the placebo. All subjects will receive an intranasal (IN) dose of either CodaVax or Leibovitz's L-15 medium (placebo).

CodaVax is a live attenuated influenza vaccine (LAIV) manufactured using a proprietary SAVE platform against the H1N1 A/California/07/2009 (H1N1) strain. The vaccination dose for cohort 1 will be 5 x 10^3 PFU in 200 microlitre of current Good Manufacturing Practice (cGMP) Leibovitz's L-15 media. Cohort 2 will be 1 x 10^5 PFU in 425 microliter and is to be administered through an intranasal sprayer into one nostril only.

In the study, due to the increase in dose to 20-fold compared to the dose in part 1 of the study, as a safety measure, 2 sentinel participants (1 placebo and 1 CodaVax participant) will receive the first dose of placebo or CodaVax by IN sprayer and Placebo by IN sprayer on Day 0 and will be monitored for 7 days. 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, 4 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.

Strategies used to monitor fidelity to the intervention is not applicable. This is only a single dose only. Accountability will be reviewed at the end of the study
Intervention code [1] 300802 0
Treatment: Drugs
Comparator / control treatment
The placebo group consists of an intranasal (IN) dose of Leibovitz's L-15 medium. The frequency of the dose will only be a single dose.
Control group
Placebo

Outcomes
Primary outcome [1] 305412 0
The primary outcome of this study is the assessment of the safety profile and tolerability of CodaVax influenza vaccine comparing it to the placebo control. This will be tested by clinical laboratory testing, physical examination, vital sign assessments, noting the frequency and types of AE and the use of concomitant medication.

Examples of adverse events that may occur are pain, swelling, nasal congestion, runny nose and sore throat.
Timepoint [1] 305412 0
daily for 6 days post vaccination
Secondary outcome [1] 345095 0
The assessment of the number of subjects with AEs after each vaccination for each treatment group by
testing clinical laboratory testing, physical examination, vital sign assessments, noting the frequency and
types of AE and the use of concomitant medication
Timepoint [1] 345095 0
At day 30 after vaccination
Secondary outcome [2] 345096 0
Assessment of the number of subjects with solicited systemic and/or local reactions observed after each
vaccination by testing clinical laboratory testing, physical examination, vital sign assessments, noting the
frequency and types of AE and the use of concomitant medication
Timepoint [2] 345096 0
Day 6 after vaccination
Secondary outcome [3] 345097 0
Assessment of the frequency and severity of each solicited systemic and local reactions (composite) after
each vaccination per treatment group by using the AE tracker log
Timepoint [3] 345097 0
Day 6 after vaccination
Secondary outcome [4] 345098 0
Assessment of the frequency and severity of AEs observed (composite) after each vaccination per
treatment group by testing clinical laboratory testing, physical examination, vital sign assessments, noting
the frequency and types of AE and the use of concomitant medication
Timepoint [4] 345098 0
Day 30 after vaccination
Secondary outcome [5] 345099 0
The assessment of the frequency of Serious Adverse Events (SAEs) observed by using the SAE tracking
log
Timepoint [5] 345099 0
At the end of the study period (day 168)
Secondary outcome [6] 345100 0
the percentage of subjects achieving an Haemagglutination Inhibition Test (HAI) antibody titre greater than equal to 1:40 compared to baseline at day 0 pre-vaccination
Timepoint [6] 345100 0
Day 30 post vaccination
Secondary outcome [7] 345101 0
the rate of seroconversion, defined as the percentage of subjects with either a pre-vaccination HAI titre
less than 1:10 and a post vaccination HAI titre greater than 1:40 or a pre-vaccination HAI titre greater or
equal to 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titre
Timepoint [7] 345101 0
day 30 post vaccination
Secondary outcome [8] 345102 0
The assessment of the Geometric mean titres (GMT) of anti-A/California/07-2009(H1N1) HAI serum antibodies per treatment group
Timepoint [8] 345102 0
day 30 post vaccination
Secondary outcome [9] 345107 0
The assessment of the Geometric mean titres (GMT) of anti-A/Michigan/45/2015 (H1N1) antiobodies
Timepoint [9] 345107 0
day 30 post vaccination
Secondary outcome [10] 345109 0
The assessment of the Geometric mean fold increase (GMFI) of anti-A/California/07/2009 (H1N1) HAI serum antibodies after each vaccination relative to baseline
Timepoint [10] 345109 0
day 30 post vaccination
Secondary outcome [11] 345110 0
The assessment of the Geometric mean fold increase (GMFI) of anti-A/Michigan/45/2015 (H1N1) HAI serum antibodies determined relative to baseline
Timepoint [11] 345110 0
day 30 post vaccination
Secondary outcome [12] 345111 0
The assessment of the proportion of seropositives. A seropositive is defined as a patient's serum HAI titre to A/California/07/2007 (H1N1) that is greater than equal to 40 HAI
Timepoint [12] 345111 0
At any time point during the study period

Eligibility
Key inclusion criteria
Inclusion criteria:

1. Adult volunteers, aged 18–45 years (at the time of screening)

2. In good health, in the opinion of the Medical Investigator (with or without the Sponsor), with no significant medical history and no clinically significant 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

3. Women of child bearing potential (WOCBP) must use highly effective, double contraception from the Screening Visit and up to the Follow-up visit (Day 30 +/- 2 days). 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.
Women of childbearing potential must have a negative serum pregnancy test at
Screening and Day 30. Women not of childbearing potential must be postmenopausal
(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.

4. Must be willing to comply with the following conditions to prevent the spread of GMOs
according the 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

5. Adequate venous access in the left or right arms to allow collection of a number of blood samples

6. No birthmarks, tattoos, wounds or other skin conditions which could reasonably obscure IM injection site reactions

7. Able to communicate effectively with study personnel and considered reliable, willing and cooperative in terms of compliance with the protocol requirements

8. Participant does not intend to start or change an existing physical conditioning regimen prior to or during the study period

9. Participant has voluntarily given written informed consent to participate in the study (prior study entry)

10. Participant is available for the duration of the study
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion criteria:

1. Immunodeficiency (including HIV) or autoimmune disorder, or participant is currently taking drugs or was undergoing a form of treatment within 6 weeks prior to study entry that affects the immune system. (Treatment of asthma with low dose corticosteroids equivalent to prednisone <10 mg/day, is permitted).

2. Received blood or blood products in the 3 months prior to screening

3. Received another vaccine within 30 days before screening

4. Received another influenza vaccine within 2 years prior to screening

5. Participated in another clinical study (involving an investigational product or device) within 60 days before screening (including studies for FluMist 'Registered Trademark')

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, asthma)

7. If female, pregnant, planning to become pregnant, or lactating

8. 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 greater than 4 standard drinks (or equivalent) per day

9. History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study

10. Current or history of significant neurological, cardiovascular, pulmonary (including asthma), hepatic, rheumatic, autoimmune, haematological, metabolic or renal disorder

11. Clinically significant abnormal laboratory value at screening as determined by the
Investigator

12. Unusual dietary habits and excessive or unusual vitamin intake likely, in the opinion of the Investigator, to affect safety pathology parameters

13. Participant is seropositive to Human Immunodeficiency Virus (HIV-1 or HIV-2), Hepatitis C Virus (HCV) or HBV.

14. Body temperature (oral) greater than or equal to 38.0 degrees Celcius or acute illness within 5 days prior to vaccination

15. Any skin marking, tattoo or blemish precluding injection site inspection.

16. 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

17. 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

18. Participant is not to have had Guillain-Barre Syndrome

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
Completed
Date of first participant enrolment
Anticipated
Actual
23/10/2017
Date of last participant enrolment
Anticipated
Actual
1/12/2017
Date of last data collection
Anticipated
1/06/2018
Actual
6/07/2018
Sample size
Target
50
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 10574 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment postcode(s) [1] 22293 0
4007 - Herston

Funding & Sponsors
Funding source category [1] 299134 0
Commercial sector/Industry
Name [1] 299134 0
Codagenix, Inc.
Country [1] 299134 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Clinical Network Services Pty Ltd
Address
Level 4, 88 Jephson Street
Toowong, QLD 4066
Country
Australia
Secondary sponsor category [1] 298393 0
Commercial sector/Industry
Name [1] 298393 0
Codagenix, Inc
Address [1] 298393 0
3 Bioscience Park Drive Farmingdale, NY 11735-0176
Country [1] 298393 0
United States of America

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300065 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 300065 0
Ethics committee country [1] 300065 0
Australia
Date submitted for ethics approval [1] 300065 0
03/10/2017
Approval date [1] 300065 0
10/10/2017
Ethics approval number [1] 300065 0

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

Contacts
Principal investigator
Name 82446 0
Dr Paul Griffin
Address 82446 0
Q-Pharm Level 6, Block 8 Royal Brisbane and Women's Hospital Herston QLD 4006
Country 82446 0
Australia
Phone 82446 0
+61 7 3845 3647
Fax 82446 0
Email 82446 0
[email protected]
Contact person for public queries
Name 82447 0
J. Robert Coleman
Address 82447 0
Codagenix Inc. 3 Bioscience Park Drive Farmingdale, NY 11735-0176
Country 82447 0
United States of America
Phone 82447 0
+1 516-448-5073
Fax 82447 0
Email 82447 0
[email protected]
Contact person for scientific queries
Name 82448 0
J. Robert Coleman
Address 82448 0
Codagenix Inc. 3 Bioscience Park Drive Farmingdale, NY 11735-0176
Country 82448 0
United States of America
Phone 82448 0
+1 516-448-5073
Fax 82448 0
Email 82448 0
[email protected]

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

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