Immunogenicity and Safety of the Concomitant Administration of OVX836 Influenza Vaccine, Quadrivalent Inactivated Influenza Vaccines and Placebo in Healthy Subjects.

NCT05734040 | Completed Phase 2

• 1 other identifier: OVX836-006
• Study Type: interventional
• Target: 478
• Locations: 1 country
• Sites: 9

Brief Summary

The present study OVX836-006 aims principally to:

• Confirm feasibility of the concomitant administration of the vaccines under normal clinical conditions, i.e. as two separate concomitant injections into opposite arms;
• Introduce an additional representative brand of Quadrivalent Inactivated Influenza Vaccines ;
• Demonstrate the absence of interaction between OVX836 and Quadrivalent Inactivated Influenza Vaccines on the Hemagglutinin response;
• Demonstrate the absence of interaction between OVX836 and Quadrivalent Inactivated Influenza Vaccines on the nucleoprotein response;
• Evaluate the absolute vaccine efficacy of OVX836 compared to placebo in order to corroborate the efficacy signals previously detected in the OVX836 previous studies;
• Evaluate the combined vaccine efficacy of OVX836 + Quadrivalent Inactivated Influenza Vaccines versus OVX836 + placebo, and versus double placebo.

Conditions

Influenza

Outcome Measures

Primary Outcomes (6)

• Number of seroconversion determined using Hemagglutination-Inhibition assay, for the four influenza strains contained in the Quadrivalent Inactivated Influenza Vaccines.

  Seroconversion is defined as a negative pre-vaccination Hemagglutination-Inhibition assay titer and post-vaccination Hemagglutination-Inhibition assay titer ≥1:40, or a fourfold increase in Hemagglutination-Inhibition assay titer between pre- and post-vaccination timepoints.

  At Day 29 versus pre-injection baseline (Day 1)

• Proportion of subjects achieving a titer ≥1:40 at Day 29 determined using Hemagglutination-Inhibition assay, for the four influenza strains contained in the Quadrivalent Inactivated Influenza Vaccine.

  At Day 29

• Number of Hemagglutination-Inhibition assay titers geometric mean ratios >2.5 for the four influenza strains contained in the Quadrivalent Inactivated Influenza Vaccines.

  At Day 29 versus pre-injection baseline (Day 1)

• Proportion of subjects reporting solicited local (Injection site redness, Injection site swelling, Injection site pain) and systemic signs and symptoms (Fatigue, Headache, Arthralgia, Malaise, Myalgia, Fever)

  During 7 days after vaccine administration

• Proportion of subjects reporting unsolicited Adverse Events

  During 29 days after vaccine administration

• Proportion of subjects reporting Serious Adverse Events

  During the whole study duration, 180 days

Secondary Outcomes (6)

• Hemagglutination-Inhibition assay geometric mean titers for each of the four strains contained in the Quadrivalent Inactivated Influenza Vaccines.

  At Day 1 (pre-injection baseline) and Day 29

• Number of laboratory-confirmed influenza A or B cases.

  During the whole study duration, 180 days

• Severity scores of Influenza-Like-Illness cases (as per Flu-PRO questionnaire)

  During the whole study duration, 180 days

• Cell-mediated immune response in terms of change of Nucleoprotein-specific T-cell frequencies in Peripheral Blood Mononuclear Cells, measured by Interferon Gamma Enzyme-Linked Immunospot Assay.

  At Day 8 versus pre-injection baseline (Day 1)

• Geometric Mean Titer of anti-Nucleoprotein immunoglobulin G (Enzyme-Linked Immunosorbent Assay, serum).

  At Day 1, Day 8 and Day 29

Study Arms (6)

OVX836 480µg + Fluarix Tetra at commercial dose

EXPERIMENTAL

OVX836: Adjuvant-free recombinant influenza candidate vaccine based on Nucleoprotein of the influenza virus. One single administration intramuscularly of 480µg dose on Day 1 AND Fluarix Tetra: Inactivated and purified split influenza vaccine. One single administration intramuscularly in the opposite arm on Day 1.

Biological: OVX836 480µg; Biological: Fluarix Tetra

OVX836 480µg + Afluria Quad at commercial dose

EXPERIMENTAL

OVX836: Adjuvant-free recombinant influenza candidate vaccine based on Nucleoprotein of the influenza virus. One single administration intramuscularly of 480µg dose on Day 1 AND Afluria Quad: Inactivated and purified split influenza vaccine. One single administration intramuscularly in the opposite arm on Day 1.

Biological: OVX836 480µg; Biological: Afluria Quad

Fluarix Tetra at commercial dose + Placebo

ACTIVE COMPARATOR

Fluarix Tetra: Inactivated and purified split influenza vaccine. One single administration intramuscularly in the opposite arm on Day 1. AND Placebo Comparator: Saline solution (B. Braun Ecoflac Plus) Saline solution (NaCl 0,9%), B. Braun Ecoflac Plus 50 milliliter. One single administration intramuscularly of a 0.8 milliliter dose in the opposite arm on Day 1.

Biological: Fluarix Tetra; Biological: Placebo

Afluria Quad at commercial dose + Placebo

ACTIVE COMPARATOR

Afluria Quad: Inactivated and purified split influenza vaccine. One single administration intramuscularly on Day 1. AND Placebo Comparator: Saline solution (B. Braun Ecoflac Plus) Saline solution (NaCl 0,9%), B. Braun Ecoflac Plus 50 milliliter. One single administration intramuscularly of a 0.8 milliliter dose in the opposite arm on Day 1.

Biological: Afluria Quad; Biological: Placebo

OVX836 480µg + Placebo

PLACEBO COMPARATOR

OVX836: Adjuvant-free recombinant influenza candidate vaccine based on Nucleoprotein of the influenza virus. One single administration intramuscularly of 480µg dose on Day 1 AND Placebo Comparator: Saline solution (B. Braun Ecoflac Plus) Saline solution (NaCl 0,9%), B. Braun Ecoflac Plus 50 milliliter. One single administration intramuscularly of a 0.8 milliliter dose in the opposite arm on Day 1.

Biological: OVX836 480µg; Biological: Placebo

Placebo + Placebo

PLACEBO COMPARATOR

Placebo Comparator: Saline solution (B. Braun Ecoflac Plus) Saline solution (NaCl 0,9%), B. Braun Ecoflac Plus 50 milliliter. One single administration intramuscularly of a 0.8 milliliter dose on Day 1 AND Placebo Comparator: Saline solution (B. Braun Ecoflac Plus) Saline solution (NaCl 0,9%), B. Braun Ecoflac Plus 50 milliliter. One single administration intramuscularly of a 0.8 milliliter dose in the opposite arm on Day 1.

Biological: Placebo

Interventions

OVX836 480µg BIOLOGICAL

One single administration intramuscularly at Day 1

OVX836 480µg + Afluria Quad at commercial dose; OVX836 480µg + Fluarix Tetra at commercial dose; OVX836 480µg + Placebo

Fluarix Tetra BIOLOGICAL

One single administration intramuscularly at Day 1

Fluarix Tetra at commercial dose + Placebo; OVX836 480µg + Fluarix Tetra at commercial dose

Afluria Quad BIOLOGICAL

One single administration intramuscularly at Day 1

Afluria Quad at commercial dose + Placebo; OVX836 480µg + Afluria Quad at commercial dose

Placebo BIOLOGICAL

One single administration intramuscularly at Day 1

Afluria Quad at commercial dose + Placebo; Fluarix Tetra at commercial dose + Placebo; OVX836 480µg + Placebo; Placebo + Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent.
• Healthy male or female subjects, as determined by medical history and medical examination.
• Aged 18 to 60 years.
• Subjects who have received at least two doses of a licensed severe acute respiratory syndrome Coronavirus 2 vaccine.
• Reliable and willing to make themselves available for the duration of the study, and willing and able to follow study procedures.
• Able to read, understand and complete an electronic diary and electronic patient reported outcome, and availability of a person who can complete the electronic diary/electronic patient reported outcome in case of illness.

You may not qualify if:

• Subjects with a body mass index ≤19 kg/m² or ≥40 kg/m² on the day of vaccination.
• Previous influenza vaccination within 6 months before the day of vaccination or planned to receive influenza vaccination during the whole study period.
• Any known or suspected immunodeficient conditions.
• Past or current history of significant autoimmune diseases, as judged by the Investigator.
• Known or suspected infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus.
• Current history of significant uncontrolled medical illness such as diabetes, hypertension, heart, renal or hepatic diseases, as judged by the Investigator.
• Planned, recent (\<6 months since completion) or ongoing gender reassignment during the study.
• Female subjects: pregnant, breast-feeding or of childbearing potential without appropriate contraceptive methods in place for 2 months before enrolment, or with positive pregnancy test on the day of vaccination. Appropriate contraceptive methods are to be maintained until the end of the trial. Appropriate contraceptive methods are defined by the Clinical Trial Facilitation Group as follow: "Contraceptive methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: combined (estrogen- and progestogencontaining) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable intrauterine device, intrauterine hormone-releasing system), bilateral tubal occlusion, vasectomized partner and/or sexual abstinence (refraining from heterosexual intercourse)."
• Having received another vaccination within 3 months prior to the day of study vaccination for live attenuated vaccines, or within 1 month prior to the day of study vaccination for inactivated vaccines, except Coronavirus Disease 2019 vaccine.
• Planning to receive other vaccines during the first 28 days following the study vaccine administration.
• Having received a Coronavirus Disease 2019 vaccination within 2 weeks prior to the day of study vaccination.
• Planning to receive Coronavirus Disease 2019 vaccine during the first week (within 7 days) following the study vaccine administration. An interval of preferably 14 days is recommended.
• Administration of any investigational (including OVX836) or non-registered drug or vaccine within 3 months prior to the administration of study vaccines, or planned administration of any such product during the whole study period.
• History of receiving blood, blood components or immunoglobulins within 3 months prior to the day of vaccination, or planned to receive such product during the whole study period.
• Long Coronavirus Disease, either ongoing or recently recovered.

Sponsors & Collaborators

• Osivax: lead
• Novotech (Australia) Pty Limited: collaborator
• Mater Misericordiae Limited: collaborator

Study Sites (9)

Paratus Clinical Research Central Coast

Kanwal, New South Wales, 2259, Australia

Location

Emeritus Research Sydney

Sydney, New South Wales, 2019, Australia

Location

Paratus Clinical Research Western Sydney

Sydney, New South Wales, 2148, Australia

Location

Paratus Clinical Research Brisbane

Brisbane, Queensland, 4010, Australia

Location

Mater Misericordiae Limited

Brisbane, Queensland, 4101, Australia

Location

UniSC Clinical Trials Moreton Bay

Morayfield, Queensland, 4506, Australia

Location

University of Sunshine Coast

Sippy Downs, Queensland, 4556, Australia

Location

CMAX Fusion Clinical Research

Adelaide, South Australia, 5000, Australia

Location

Emeritus

Melbourne, Victoria, 3124, Australia

Location

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized (1:1:1:1:1:1) into 6 groups of 100 subjects to receive: * First group: OVX836 480µg and Fluarix Tetra at commercial dose administered intramuscularly concomitantly into opposite arms. * Second group: OVX836 480µg and Afluria Quad at commercial dose administered intramuscularly concomitantly into opposite arms. * Third group: OVX836 480µg, concomitantly administered with placebo, intramuscularly into opposite arms. * Fourth group: Fluarix Tetra at commercial dose, concomitantly administered with placebo, intramuscularly into opposite arms. * Fifth group: Afluria Quad at commercial dose, concomitantly administered with placebo, intramuscularly into opposite arms. * Sixth group: placebo administered intramuscularly as two concomitant injections into opposite arms.

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: February 17, 2023
• Study Start: May 10, 2023
• Primary Completion: August 10, 2023
• Study Completion: January 15, 2024
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (9)