Immunogenicity, Safety and Tolerability of a Plant-Derived Seasonal VLP Quadrivalent Influenza Vaccine in the Elderly Population

NCT02236052 | Completed Phase 2 DMC

• 1 other identifier: CP-Q13VLP-008
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 3

Brief Summary

This is a multiple sites phase II trial, randomized, observer-blind, dose ranging, placebo-controlled study to evaluate the immunogenicity, safety, and tolerability of a single intramuscular injection of plant-based Seasonal VLP Quadrivalent Influenza Vaccine administered in elderly subjects (50 years old and more). A total of four hundred fifty (450) subjects will be randomized in six (6) groups of 75 subjects to receive one injection of either a non-adjuvanted low, medium or high dose level of VLP, a low or high dose level of VLP of the quadrivalent VLP influenza vaccine combined with Alhydrogel® as adjuvant or the placebo preparation (100 millimolar (mM) phosphate buffer + 150 mM sodium chloride (NaCl) + 0.01% Tween 80)

Conditions

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

Keywords

Influenza; Human; RNA Virus Infections; Immunologic; Immunogenic Factors; Physiological Effects of Drugs; Virus diseases; Orthomyxoviridae Infections; Infection

Outcome Measures

Primary Outcomes (2)

• Immunogenicity

  Immunogenicity will be assessed by Geometric mean titers (GMTs) of Hemagglutination Inhibition (HI) antibodies against the vaccine strains on Days 0 and 21 and assessed by measuring geometric mean fold rise, seroconversion rate and seroprotection rate. Follow-up serology samples for GMTs will be collected at Day 201.

  21 days after injection

• Solicited systemic and local reactions

  Safety and tolerability will be assessed by the rate, severity and relationship to vaccination of solicited and unsolicited adverse events post-vaccination. A 6-month follow-up period will be performed.

  21 days after injection

Secondary Outcomes (1)

• Immunogenicity (against vaccine strains and heterologous strains)

  21 days after injection

Study Arms (6)

Non-adjuvanted low dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single non-adjuvanted low dose of quadrivalent VLP vaccine

Biological: Non-adjuvanted low dose of quadrivalent VLP vaccine

Non-adjuvanted medium dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single non-adjuvanted medium dose of quadrivalent VLP vaccine

Biological: Non-adjuvanted medium dose of quadrivalent VLP vaccine

Non-adjuvanted high dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single non-adjuvanted high dose of quadrivalent VLP vaccine

Biological: Non-adjuvanted high dose of quadrivalent VLP vaccine

Adjuvanted low dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®

Biological: Adjuvanted low dose of quadrivalent VLP vaccine

Adjuvanted high dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®

Biological: Adjuvanted high dose of quadrivalent VLP vaccine

Placebo

PLACEBO COMPARATOR

A single dose of Placebo

Biological: Placebo

Interventions

Non-adjuvanted low dose of quadrivalent VLP vaccine BIOLOGICAL

A single non-adjuvanted low dose of quadrivalent VLP vaccine

Non-adjuvanted low dose of quadrivalent VLP vaccine

Non-adjuvanted medium dose of quadrivalent VLP vaccine BIOLOGICAL

A single non-adjuvanted medium dose of quadrivalent VLP vaccine

Non-adjuvanted medium dose of quadrivalent VLP vaccine

Non-adjuvanted high dose of quadrivalent VLP vaccine BIOLOGICAL

A single non-adjuvanted high dose of quadrivalent VLP vaccine

Non-adjuvanted high dose of quadrivalent VLP vaccine

Adjuvanted low dose of quadrivalent VLP vaccine BIOLOGICAL

A single low dose of quadrivalent VLP vaccine mixed with Alhydrogel®

Adjuvanted low dose of quadrivalent VLP vaccine

Adjuvanted high dose of quadrivalent VLP vaccine BIOLOGICAL

A single high dose of quadrivalent VLP vaccine mixed with Alhydrogel®

Adjuvanted high dose of quadrivalent VLP vaccine

Placebo BIOLOGICAL

A single dose of placebo

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female subjects, 50 years of age or older.
• BMI of ≥18 and ≤32.
• Give his/her consent to participate in this study (by signing the informed consent form). In the opinion of the Investigator, competence and willingness to provide written, informed consent for participation after reading the informed consent form. The subject must have adequate opportunity to discuss the study with an Investigator or qualified designee.
• Healthy as judged by the Investigator or designee and determined by general physical examination, vital signs, clinical laboratory tests, and medical history conducted no more than 90 days prior to study vaccine administration. Subjects with a pre-existing chronic disease will be allowed to participate if the disease is stable and, according to the Investigator's judgment, the condition is unlikely confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is defined as no new onset of exacerbation of pre-existing chronic disease 6 months prior to immunization. Based on Investigator's judgment, a subject with more recent stabilisation of a disease may still be eligible.
• Comprehension of the study requirements, expressed availability for the required study period, ability to attend scheduled visits, accessible by phone on a consistent basis.
• If female, have a negative serum pregnancy test result at screening and negative urine pregnancy test on Day 0 prior to immunization.
• Female of childbearing potential must use an effective method of contraception for 1 month prior to immunization and agrees to continue employing adequate birth control measures for at least 60 days post-immunization. Moreover, she must have no plan to become pregnant for at least 2 months post-immunization. Abstinent subjects should be asked what method(s) they would use, should their circumstances change, and subjects without a well-defined plan should be excluded.
• The following relationship or methods of contraception are considered to be effective:
• Hormonal contraceptives (e.g., injectable, topical \[patch\], estrogenic vaginal ring, etc.);
• Intra-uterine device (IUD) with or without hormonal release;
• Male partner using a condom plus spermicide or sterilized partner (at least 1 year prior to immunization);
• History of credible abstinence (self-reported);
• Heterosexual abstinence at least 60 days post-immunization;
• Female partner.
• Non-childbearing females defines as:

You may not qualify if:

• According to Investigator's opinion, presence of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. "Uncontrolled" is defined as:
• Requiring a new medical or surgical treatment within one month prior to study vaccine administration which would interfere with vaccine evaluation or study completion (subject requiring medical or surgical treatment that would not interfere with evaluation \[e.g., minor knee surgery, cataracts, etc.\] would be eligible);
• Requiring a change in medication dosage in one month prior to study vaccine administration due to uncontrolled symptoms or drug toxicity (elective dosage adjustments in stable subjects are acceptable).
• Any medical or neuropsychiatric condition or any history of excessive alcohol use or drug abuse which, in the Investigator's opinion, would render the subject unable to provide informed consent or unable to provide valid safety observations and reporting.
• Any autoimmune disease or any confirmed or suspected immunosuppressive condition or immunodeficiency including history of human immunodeficiency virus (HIV) infection, Hepatitis B or C, or the presence of lymphoproliferative disease.
• Administration of any vaccine (including any other influenza vaccine) within 30 days prior to study enrolment or planned administration within the period from the vaccination up to blood sampling at Day 21 or within 30 days prior to blood sampling at Day 201. Immunization on an emergency basis will be evaluated in a case-by-case by the Investigator.
• Use of any investigational or non-registered product within 30 days prior to study enrolment or planned use during the study period. Subjects may not participate in any other investigational or marketed drug study while participating in this study (approximately 7-12 months \[depending when subjects undergo screening session and Day 201 visit\]).
• Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone per day, or equivalent for more than 7 consecutive days or for 10 or more days in total, within one month of study vaccine administration, any other cytotoxic or immunosuppressant drug, or any immunoglobulin preparation within 3 months of vaccination. Routine use of standard doses of nasal or inhaled glucocorticoids is allowed.
• Any significant disorder of coagulation or treatment with warfarin derivatives or heparin. Persons receiving prophylactic anti-platelet medications, e.g., low-dose aspirin (no more than 325 mg/day), and without a clinically apparent bleeding tendency are eligible. Subjects treated with new generation drugs that will not increase risk of intramuscular bleeding (such as clopidogrel) are also eligible.
• History of allergy to any of the constituents of the VLP quadrivalent study vaccine, Alhydrogel® (aluminum hydroxide) or to the phosphate buffered saline (PBS; used as placebo), or tobacco allergy.
• History of anaphylaxis reaction to any food, medication or bee sting.
• Any history of severe asthma (e.g., status asthmatic, hospitalization for asthma control) or recurrent asthma episodes requiring medical attention in the last 3 years (≥ 1 episode/year).
• Continuous use of anti-histamines in the last 4 weeks prior to immunization or use of anti-histamines 48 hours prior to study immunization.
• Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site which may interfere with injection site reaction rating.
• Have received a blood transfusion within 90 days prior to study vaccination.

Sponsors & Collaborators

• Medicago: lead

Study Sites (3)

MUHC-Vaccine Study Centre

Pierrefonds, Quebec, H9H 4Y6, Canada

Location

Centre de recherche-CHU de Québec

Québec, G1E 7G9, Canada

Location

inVentiv Health Clinique

Québec, G1P 0A2, Canada

Location

Related Publications (1)

• Pillet S, Couillard J, Trepanier S, Poulin JF, Yassine-Diab B, Guy B, Ward BJ, Landry N. Immunogenicity and safety of a quadrivalent plant-derived virus like particle influenza vaccine candidate-Two randomized Phase II clinical trials in 18 to 49 and >/=50 years old adults. PLoS One. 2019 Jun 5;14(6):e0216533. doi: 10.1371/journal.pone.0216533. eCollection 2019.

  PMID: 31166987 RESULT

MeSH Terms

Conditions

Virus Diseases; RNA Virus Infections; Respiratory Tract Diseases; Respiratory Tract Infections; Influenza, Human; Orthomyxoviridae Infections; Infections

Study Officials

• Michael Libman, MD

  MUHC-Vaccine Study Centre

  PRINCIPAL INVESTIGATOR

• Guy Boivin, MD

  Centre de recherche-CHU de Québec

  PRINCIPAL INVESTIGATOR

• Richard Larouche, MD

  inVentiv Health Clinique

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 10, 2014
• Study Start: July 16, 2014
• Primary Completion: June 17, 2015
• Study Completion: June 17, 2015
• Last Updated: November 1, 2019

Record last verified: 2019-10

Locations

CA (3)