Safety Study of Live Attenuated Influenza Vaccine, CodaVax

A Randomised, Double-Blind, Double-Dummy, Active and Placebo Controlled Phase I Trial of the Safety, Tolerability and Immunogenicity of the CodaVax Influenza Vaccine

This study is being conducted to assess the safety, tolerability, and immunogenicity of the CodaVax-H1N1 influenza vaccine as compared to active and placebo controls when administered to healthy adults.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: CodaVax-H1N1; Biological: Fluzone quadrivalent

Detailed Description

This randomized, double-blind, placebo and active controlled Phase I study is intended to study the effects of a live-attenuated vaccine against influenza A H1N1. Part 1 of this study will enroll 75 participants at a single site. Participants will be randomized in a 2:2:1 ratio to receive one dose each of either CodaVax-H1N1, FluZone quadrivalent, or placebo. This study is conducted during the influenza "off season" in Australia. Part 2 of the study will enroll an 50 additional participants randomized to receive either CodaVax-H1N1 at a higher dose or placebo (40:10).

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Herston, Queensland, Australia, 4006
      • Q-Pharm

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 drug history identifying any known drug allergies and the presence of drug abuse;
  • Any chronic use of medication(s); and
  • Thorough review of body systems

• 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:

  • Established hormonal contraception (with approved oral, injected or depot regimen) for at least 2 months prior to screening
  • Depot or injectable birth control
  • Intrauterine device or intrauterine system in place for at least 2 months prior to screening
  • 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.

• Must be willing to comply with the following conditions to prevent the spread of GMOs according the OGTR Licence (DIR 144):

  1. 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
  2. Blood, tissue or organs must not be donated within 7 days of vaccination
  3. Severely immunosuppressed persons who require a protective environment are not to be cared for by the participant within 7 days of vaccination
  4. Contact is not to be made with severely immunosuppressed persons who require a protective environment within 7 days of vaccination
  5. 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
• Adequate venous access in the left or right arms to allow collection of a number of blood samples
• No birthmarks, tattoos, wounds or other skin conditions which could reasonably obscure IM injection site reactions
• Able to communicate effectively with study personnel and considered reliable, willing and cooperative in terms of compliance with the protocol requirements
• Participant does not intend to start or change an existing physical conditioning regimen prior to or during the study period
• Participant has voluntarily given written informed consent to participate in the study (prior study entry)
• Participant is available for the duration of the study

Exclusion Criteria:

• 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).
• Participant is not to have had Guillain-Barre Syndrome
• Received blood or blood products in the 3 months prior to screening
• Received another vaccine within 30 days before screening
• Received another influenza vaccine within 2 years prior to screening
• Participated in another clinical study (involving an investigational product or device) within 60 days before screening (including studies for FluMist®)
• 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)
• Participants with active asthma currently managed by ad lib with inhalers
• Participants with a known egg allergy
• If female, pregnant, planning to become pregnant, or lactating
• 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
• History of any psychiatric illness or psychological disorder which may impair the ability to provide written informed consent or participate in the study
• Current or history of significant neurological, cardiovascular, pulmonary (including asthma), hepatic, rheumatic, autoimmune, haematological, metabolic or renal disorder
• Clinically significant abnormal laboratory value at screening as determined by the Investigator
• Unusual dietary habits and excessive or unusual vitamin intake likely, in the opinion of the Investigator, to affect safety pathology parameters
• Participant is seropositive to Human Immunodeficiency Virus (HIV-1 or HIV-2), Hepatitis C Virus (HCV) or HBV.
• Body temperature (oral) ≥38.0ºC or acute illness within 5 days prior to vaccination
• Any skin marking, tattoo or blemish precluding injection site inspection.
• 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
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CodaVax-H1N1, low dose; Participants will receive a single dose of either CodaVax (5 x 10^3 PFU in 200 uL) and an intramuscular injection of placebo	Biological: CodaVax-H1N1; Live-attenuated vaccine against influenza A H1N1, A/California/07/2009
ACTIVE_COMPARATOR: Fluzone; Participants will receive an intranasal (IN) dose of placebo and an intramuscular (IM) dose of QuadriFlu- Tetravalent Influenza Vaccine (TIV) (Fluzone®)	Biological: Fluzone quadrivalent; Fluzone® (QuadriFlu - TIV), inactivated, quadrivalent influenza vaccine
EXPERIMENTAL: CodaVax-H1N1, high dose; Participants will receive a single intranasal (IN) dose of CodaVax-H1N1 (1 x 10^5 PFU in 500 uL)	Biological: CodaVax-H1N1; Live-attenuated vaccine against influenza A H1N1, A/California/07/2009
PLACEBO_COMPARATOR: Placebo; Leibovitz's L-15 medium (IN) or saline (IM)	Biological: CodaVax-H1N1; Live-attenuated vaccine against influenza A H1N1, A/California/07/2009; Biological: Fluzone quadrivalent; Fluzone® (QuadriFlu - TIV), inactivated, quadrivalent influenza vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with solicited local and/or systemic reactions after each vaccination, for each treatment group	Number of volunteers that experience adverse events	6 days
Incidence of Adverse Events (AE)	Number of subjects with AEs	30 days
Incidence of Serious Adverse Events (SAE)	Number of subjects with SAEs	Days 1-168

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemagglutination Inhibition Test (HAI) titre	The percentage of subjects achieving a (HAI) antibody titre ≥ 1:40 determined 30 days post-vaccination as compared to baseline (Day 0, pre-vaccination)	30 days post-vaccination
Rate of Seroconversion	The rate of seroconversion, defined as the percentage of subjects with either a pre-vaccination HAI titre < 1:10 and a post vaccination HAI titre > 1:40 or a pre-vaccination HAI titre > or = to 1:10 and a minimum four-fold rise in post-vaccination HAI antibody titre, determined 30 days postvaccination	30 days post-vaccination
Cal/09 HAI antibodies	Geometric mean titres (GMT) of anti-A/California/07/2009 (H1N1) HAI serum antibodies 30 days after each vaccination, by treatment group	30 days post-vaccination
Mich/15 HAI antibodies	Geometric mean titres (GMT) of anti-A/Michigan/45/2015 (H1N1) antibodies (HAI); Geometric mean fold increase (GMFI) of anti-A/California/07/2009 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline; Geometric mean fold increase (GMFI) of anti-A/Michigan/45/2015 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline	30 days post-vaccination
Increase in anti-Cal/09 antibodies	Geometric mean fold increase (GMFI) of anti-A/California/07/2009 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline	30 days post-vaccination
Increase in anti-Mich/15 antibodies	Geometric mean fold increase (GMFI) of anti-A/Michigan/45/2015 (H1N1) HAI serum antibodies determined 30 days after each vaccination relative to baseline	30 days post-vaccination

Collaborators and Investigators

• Sponsor: Codagenix, Inc

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 21, 2017
• Primary Completion (ACTUAL): May 29, 2018
• Study Completion (ACTUAL): September 14, 2018

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (ACTUAL): April 24, 2019

Study Record Updates

• Last Update Posted (ACTUAL): July 23, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: influenza vaccine; vaccines; live-attenuated vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: CODA01-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes