Immunogenicity, Safety and Tolerability of a Plant-Derived Seasonal Virus-Like-Particle Quadrivalent Influenza Vaccine in Adults

NCT02233816 | Completed Phase 2 DMC

• 1 other identifier: CP-Q13VLP-007
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

Brief Summary

A phase II trial multicenter, observer-blind, randomized, dose-ranging, placebo-controlled study to evaluate the immunogenicity, safety, and tolerability of a single intramuscular injection of plant-derived Seasonal VLP Quadrivalent Influenza Vaccine administered to healthy adults 18-49 years of age. A total of three hundred subjects will be randomized in four (4) groups of 75 subjects to receive one injection of either a low, a medium, or a high dose level of the quadrivalent VLP influenza vaccine 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 (against vaccine strains)

  Immunogenicity will be assessed by Geometric mean titers (GMTs) of hemagglutination inhibition (HI antibody on Days 0 and 21) antibodies against the vaccine strains 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

• Safety

  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 (4)

Low dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single low dose of quadrivalent VLP vaccine

Biological: Low dose of quadrivalent VLP vaccine

Medium dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single medium dose of quadrivalent VLP vaccine

Biological: Medium dose of quadrivalent VLP vaccine

High dose of quadrivalent VLP vaccine

EXPERIMENTAL

A single high dose of quadrivalent VLP vaccine

Biological: High dose of quadrivalent VLP vaccine

Placebo

PLACEBO COMPARATOR

A single dose of Placebo

Biological: Placebo

Interventions

Low dose of quadrivalent VLP vaccine BIOLOGICAL

A single low dose of quadrivalent VLP vaccine

Low dose of quadrivalent VLP vaccine

Medium dose of quadrivalent VLP vaccine BIOLOGICAL

A single medium dose of quadrivalent VLP vaccine

Medium dose of quadrivalent VLP vaccine

High dose of quadrivalent VLP vaccine BIOLOGICAL

A single high dose of quadrivalent VLP vaccine

High dose of quadrivalent VLP vaccine

Placebo BIOLOGICAL

A single dose of placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female adults, 18 to 49 years of age, inclusive.
• Body mass index (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 complete general physical examination, vital signs, clinical laboratory tests, and medical history conducted no more than 30 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 to confound the results of the study or pose additional risk to the subject by participating in the study. Stable disease is generally defined as no new onset of exacerbation of pre-existing chronic disease 6 months prior to immunization. Based on the Investigator's judgment, a subject with more recent stabilization of a disease could also 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);
• Credible history of 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;
• 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 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 8 months).
• 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. Low doses of nasal or inhaled glucocorticoids are 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, or to the phosphate buffered saline (PBS; used as placebo), or tobacco allergy.
• History of anaphylactic allergic reactions to any food, medication or bee sting.
• Any history of asthma (eg: 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 (2)

Broward Research Group

Hollywood, Florida, 33024, United States

Location

Miami Research Associates

Miami, Florida, 33143, United States

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

• Eric Sheldon, MD

  Miami Research Associate

  PRINCIPAL INVESTIGATOR

• David J Seiden, MD

  Broward Research Group

  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 4, 2014
• First Posted: September 8, 2014
• Study Start: July 28, 2014
• Primary Completion: June 22, 2015
• Study Completion: June 22, 2015
• Last Updated: November 13, 2019

Record last verified: 2019-11

Locations

US (2)