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Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03301051
Recruitment Status : Completed
First Posted : October 4, 2017
Last Update Posted : November 2, 2020
Information provided by (Responsible Party):

Brief Summary:
This Phase 3 study is intended to assess the efficacy of the Quadrivalent VLP Influenza Vaccine during the 2017-2018 influenza season in healthy adults 18 to 64 years of age. One dose of Quadrivalent Virus-Like Particles (VLP) Influenza Vaccine (30 μg/strain) or of placebo will be administered to approximately 10,000 subjects.

Condition or disease Intervention/treatment Phase
Virus Diseases RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Biological: Quadrivalent VLP Vaccine Biological: Placebo Phase 3

Detailed Description:

This randomized, observer-blind, placebo-controlled multicenter, Phase 3 study will be conducted at multiple sites. The composition of the Quadrivalent VLP Influenza Vaccine to be used in this study includes a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs for the 2017-2018 influenza virus strains.

Approximately 10,000 healthy male and female subjects aged 18 to 64 years will be randomized in a 1:1 ratio into one of two parallel treatment groups, such that approximately 5,000 subjects will receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and approximately 5,000 subjects will receive the placebo. Within the two treatment groups, subjects will be stratified by site and two age groups (18-49 years of age and 50-64 years of age in a 1:1 ratio).

Subjects will participate in this study for approximately eight to ten months, during which a first visit will be scheduled on Day 0 for screening and vaccine administration.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10137 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Randomized, Observer-blind, Placebo-controlled, Multicenter, Phase 3 Study to Assess the Efficacy, Safety, and Immunogenicity of a Plant-Derived Quadrivalent Virus-Like Particles Influenza Vaccine in Adults 18-64 Years of Age
Actual Study Start Date : August 31, 2017
Actual Primary Completion Date : May 2, 2018
Actual Study Completion Date : June 12, 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Quadrivalent VLP Vaccine
Single dose - 30 µg/strain of Quadrivalent VLP Vaccine
Biological: Quadrivalent VLP Vaccine
Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine
Other Name: 30 µg/strain of Quadrivalent VLP Vaccine

Placebo Comparator: Placebo
Single dose - Placebo
Biological: Placebo
Single dose of a Placebo

Primary Outcome Measures :
  1. Time of occurence of protocol-defined respiratory illness due to laboratory-confirmed influenza caused by vaccine matched strains. [ Time Frame: 8 months ]

Secondary Outcome Measures :
  1. Time of occurence of protocol-defined respiratory illness due to any laboratory-confirmed influenza strains. [ Time Frame: 8 months ]
  2. Number of subjects with solicited local and systemic reactions, unsolicited adverse events, serious adverse events and New Onset Chronic Diseases. [ Time Frame: 8 months ]
  3. Immunogenicity evaluated by the humoral immune response (HI, MN, and SRH assays) and the CMI response [ Time Frame: 21 days after injection ]
    • To assess, in a subset of 400 subjects, the immunogenicity of a single dose of Quadrivalent VLP Influenza Vaccine given at a dose of 30 μg/strain or placebo, as measured by hemagglutination inhibition (HI) assay, microneutralization (MN) assay, and single radial hemolysis (SRH) assay against homologous and heterologous (HI only) influenza strains.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for participation in this study; no protocol waivers are allowed:

  1. Subjects must be able to read, understand, and sign the informed consent form (ICF); complete study-related procedures; and communicate with the study staff at visits and by phone;
  2. Subject must have a body mass index (BMI) below 40 kg/m2;
  3. Subjects are considered by the Investigator to be reliable and likely to cooperate with the assessment procedures and be available for the duration of the study;
  4. Male and female subjects must be 18 to 64 (has not yet had his/her 65th birthday) years of age, inclusive, at the Screening/Vaccination visit (Visit 1);
  5. Subjects must be in good general health prior to study participation, with no clinically relevant abnormalities that could jeopardize subject safety or interfere with study assessments, as assessed by the Principal Investigator or sub-Investigator (thereafter referred as Investigator) and determined by medical history, physical examination, and vital signs; Note: 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 or exacerbation of pre-existing chronic disease three months prior to vaccination. Based on the Investigator's judgment, a subject with more recent stabilization of a disease could also be eligible.
  6. Female subjects must have a negative urine pregnancy test result at the Screening/Vaccination visit (Visit 1);
  7. Female subjects of childbearing potential must use an effective method of contraception for one month prior to vaccination and agree to continue employing adequate birth control measures for at least 60 days post-vaccination. Moreover, female subjects must have no plan to become pregnant for at least two months post-vaccination. 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. oral, injectable, topical [patch], or estrogenic vaginal ring);
    • Intra-uterine device with or without hormonal release;
    • Male partner using a condom plus spermicide or sterilized partner (at least one year prior to vaccination);
    • Credible self-reported history of heterosexual vaginal intercourse abstinence until at least 60 days post-vaccination;
    • Female partner;
  8. Non-childbearing females are defined as:

    • Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to vaccination); or
    • Post-menopausal (absence of menses for 24 consecutive months and age consistent with natural cessation of ovulation).

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participating in this study; no protocol waivers are allowed:

  1. Any subject whose medical condition(s) is sufficiently severe that annual influenza vaccination would be routinely recommended in the jurisdiction of recruitment, as per the Investigator's judgement;
  2. According to the Investigator's opinion, history of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. 'Uncontrolled' is defined as:

    • Requiring a new medical or surgical treatment during the three months prior to study vaccine administration unless the criteria outlined in inclusion criterion no. 5 can be met (i.e. the Investigator can justify inclusion based upon the innocuous nature of medical/surgical events and/or treatments);
    • Requiring any significant change in a chronic medication (i.e. drug, dose, frequency) during the three months prior to study vaccine administration due to uncontrolled symptoms or drug toxicity unless the innocuous nature of the medication change meets the criteria outlined in inclusion criterion no. 5 and is appropriately justified by the Investigator.
  3. 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;
  4. Any autoimmune disease other than hypothyroidism on stable replacement therapy (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, and inflammatory bowel disease) or any confirmed or suspected immunosuppressive condition or immunodeficiency including known or suspected human immunodeficiency virus (HIV), Hepatitis B or C infection, the presence of lymphoproliferative disease;
  5. History of chronic pulmonary (including asthma, bronchopulmonary dysplasia, and cystic fibrosis) or cardiovascular (except isolated hypertension), renal, hepatic, neurologic, hematologic (including anemia and hemoglobinopathy), or metabolic disorders (including diabetes mellitus);
  6. Because this is a placebo-controlled study, any subjects in close contact with individuals considered to be at high risk for developing influenza-related complications (individuals considered at high risk for complications include adults and children who have chronic pulmonary or cardiovascular [except isolated hypertension], renal, hepatic, neurologic, hematologic, or metabolic disorders [including diabetes mellitus]), ;
  7. Administration or planned administration of any non-influenza vaccine within 30 days prior to randomization up to blood sampling on Day 21. Immunization on an emergency basis will be evaluated case-by-case by the Investigator;
  8. Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;
  9. Administration of any 'standard', non-adjuvanted influenza vaccine (e.g. live attenuated trivalent/quadrivalent inactivated influenza vaccine or split trivalent/quadrivalent inactivated influenza vaccine administered by intranasal, intradermal, or intramuscular route) within six months prior to randomization and up to completion of the study;
  10. Use of any investigational or non-registered product within 30 days or five half-lives, whichever is longer, prior to randomization or planned use during the study period. Subjects may not participate in any other investigational or marketed drug study while participating in this study until after the study;
  11. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven 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 three months of vaccination and until the completion of the study. Low doses of nasal or inhaled glucocorticoids are allowed. Topical steroids are permitted;
  12. Any significant disorder of coagulation including, but not limited to, 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 do not increase the risk of intramuscular bleeding (e.g. clopidogrel) are also eligible;
  13. History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine or tobacco;
  14. History of anaphylactic allergic reactions to plants or plants components;
  15. Use of antihistamines with systemic absorption for more than 14 days in the four weeks prior to vaccination or use of antihistamines 48 hours prior to study vaccination (the use of topical antihistamines and nasal or inhaled steroids is acceptable);
  16. Use of prophylactic medications (e.g. acetaminophen/paracetamol, aspirin, naproxen, or ibuprofen) within 24 hours of randomization to prevent or pre-empt symptoms due to vaccination. Any subject discovered to have taken a prophylactic medication to prevent or pre-empt symptoms due to vaccination within the 24 hours prior to planned randomization must be delayed until at least the 24 hours period is met;
  17. Planned use of influenza antiviral treatment medication before the collection of nasopharyngeal swabs (e.g. oseltamivir, zanamivir, rapivab);
  18. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating;
  19. Subjects who have received a blood transfusion within 90 days prior to study vaccination;
  20. Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;
  21. Subjects with abnormal vital signs (systolic blood pressure [BP] > 140 mmHg and/or diastolic BP ≥ 90 mmHg, heart rate ≤ 45 beats/min and ≥ 100 beats/min) evaluated by an Investigator to be clinically significant. A subject with abnormal vital signs results may be included in the study based on Investigator's judgment (e.g. a resting hear rate ≤ 45 in highly trained athletes);
  22. Presence of any febrile illness (including an oral temperature ≥ 38.0 ˚C within 24 hours prior to vaccination. Such subjects may be re-evaluated for enrolment after resolution of illness;
  23. Cancer or treatment for cancer within three years prior to study vaccine administration.

    Persons with a history of cancer who are disease-free without treatment for three years or more are eligible. However, individuals with conditions such as treated and uncomplicated basal cell carcinoma of the skin or non-treated, non-disseminated local prostate cancer may be eligible;

  24. Subjects identified as an Investigator or employee of the Investigator or clinical site with direct involvement in the proposed study, or identified as an immediate family member (i.e. parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study or any employee of Medicago;
  25. Subjects with a history of Guillain-Barré Syndrome.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03301051

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Sponsors and Collaborators
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Study Director: Brian J Ward, MD Medicago
Publications of Results:
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Responsible Party: Medicago Identifier: NCT03301051    
Other Study ID Numbers: CP-PRO-QVLP-012
First Posted: October 4, 2017    Key Record Dates
Last Update Posted: November 2, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Medicago:
RNA Virus Infections
Immunogenic Factors
Physiological Effects of Drug
Virus Diseases
Orthomyxoviridae Infections
Additional relevant MeSH terms:
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Communicable Diseases
Virus Diseases
Influenza, Human
Respiratory Tract Infections
RNA Virus Infections
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Orthomyxoviridae Infections
Immunologic Factors
Physiological Effects of Drugs