Efficacy of a Plant-derived Quadrivalent Virus-like Particle (VLP) Vaccine in the Elderly

NCT ID: NCT03739112

Last Updated: 2023-06-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 12794 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-18
• Study Completion Date: 2019-07-16

Brief Summary

This Phase 3 study was intended to assess the relative efficacy of the Quadrivalent VLP Influenza Vaccine during the 2018-2019 influenza season compared to a licensed vaccine in elderly adults 65 years of age and older. One dose of VLP Influenza Vaccine (30 μg/strain) or of Comparator (15 μg/strain) was to be administered to 12,738 participants.

Detailed Description

This randomized, observer-blind, active-controlled multicenter, Phase 3 study was conducted at multiple sites. The composition of the Quadrivalent VLP Influenza Vaccine used in this study included a mix of recombinant H1, H3, and two B hemagglutinin proteins expressed as VLPs for the 2018-2019 influenza virus strains.

A total of 12,794 healthy male and female participants aged 65 years and older were randomized in a 1:1 ratio into one of two parallel treatment groups, such that 6,396 participants were randomized to receive the Quadrivalent VLP Influenza Vaccine at a dose of 30 μg/strain and 6,398 participants were randomized to receive the comparator. Within the two treatment groups, participants were stratified by site and two age groups (65-74 years of age and 75 years of age and older in a 2:1 ratio).

Participants participated in this study for approximately nine months, during which a first visit was scheduled on Day 0 for screening and vaccine administration.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Quadrivalent VLP Vaccine

Participants received one intramuscular (IM) injection of 0.5 mL of 30 μg/strain of the Quadrivalent VLP Influenza Vaccine on Day 0.

Group Type: EXPERIMENTAL

Quadrivalent VLP Vaccine

Intervention Type: BIOLOGICAL

Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine

Fluarix Quadrivalent® Comparator Vaccine

Participants received one IM injection of 0.5 mL of 15 μg/strain of the Fluarix Quadrivalent® comparator vaccine on Day 0.

Group Type: ACTIVE_COMPARATOR

Fluarix Quadrivalent® Comparator Vaccine

Intervention Type: BIOLOGICAL

Single dose of a 15 μg/strain of Fluarix Quadrivalent® Comparator Vaccine

Interventions

Quadrivalent VLP Vaccine

Single dose of a 30 µg/strain of Quadrivalent VLP Vaccine

Intervention Type: BIOLOGICAL

Fluarix Quadrivalent® Comparator Vaccine

Single dose of a 15 μg/strain of Fluarix Quadrivalent® Comparator Vaccine

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Participants must have read, understood, and signed the informed consent form (ICF) prior to participating in the study; participants must also complete study-related procedures and communicate with the study staff at visits and by phone during the study;

2. Participants must have a body mass index (BMI) ≤35 kg/m^2;

3. Participants 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 participants must be 65 years of age and older at the Screening/Vaccination visit (Visit 1);

5. Participants must be non-institutionalized (e.g. not living in rehabilitation centres or old-age homes; living in an elderly community is acceptable) and have no acute or evolving medical problems prior to study participation and no clinically relevant abnormalities that could jeopardize participant 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: Participants with a pre-existing chronic disease are 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 participant 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 participant with more recent stabilization of a disease could also be eligible.

Exclusion Criteria

1. According to the Investigator's opinion, history of an ongoing acute or evolving medical or neuropsychiatric illness. 'Evolving' was 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.

2. Any medical or neuropsychiatric condition or any history of excessive alcohol use or drug abuse that would render the participant unable to provide informed consent or unable to provide valid safety observations and reporting, including methadone (methadone as treatment for opioid dependence may be acceptable if the participant has been otherwise opioid-free for at least three years);

3. Any autoimmune disease other than hypothyroidism on stable replacement therapy (including, but not limited to rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, type 1 diabetes, 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;

4. Any history of status asthmaticus or ongoing serious problems with asthma, hospitalization for asthma control, or recurrent asthma episodes requiring medical attention in the last three years (one or more episodes per year);

5. 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 was evaluated case-by-case by the Investigator;

6. Administration of any adjuvanted or investigational influenza vaccine within one year prior to randomization or planned administration prior to the completion of the study;

7. 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 IM route) within six months prior to randomization and up to completion of the study;

8. 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. Participants may not participate in any other investigational or marketed drug study while participating in this study until after the study;

9. Treatment with systemic glucocorticoids at a dose exceeding 10 mg of prednisone (or equivalent) per day for more than seven consecutive days or for ten 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;

10. 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 100 mg/day]), and without a clinically apparent bleeding tendency are eligible. Participants treated with new generation drugs that do not increase the risk of IM bleeding (e.g. clopidogrel) are also eligible;

11. History of allergy to any of the constituents of the Quadrivalent VLP Influenza Vaccine, any components of the active comparator quadrivalent vaccine, or tobacco;

12. History of anaphylactic allergic reactions to plants or plants components (including fruits and nuts);

13. Use of antihistamines within 48 hours prior to study vaccination;

14. Daily use of large doses of medication for pain control or inflammation (e.g. opioids, nonsteroidal anti-inflammatory drugs [NSAIDs]). Use of a singular regular dose either in the morning or at bedtime would not be exclusionary;

15. 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;

16. Planned use of influenza antiviral treatment medication before the collection of nasopharyngeal (NP) swabs (e.g. oseltamivir, zanamivir, rapivab);

17. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at the injection site that may interfere with injection site reaction rating;

18. Participants who have received a blood transfusion within 90 days prior to study vaccination;

19. Participants with abnormal vital signs (systolic blood pressure [BP] ≥ 150 mmHg and/or diastolic BP ≥ 95 mmHg for individuals taking antihypertensive medication and ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg for individuals not taking antihypertensive medication; heart rate [HR] ≤ 45 beats/min and ≥ 100 beats/min) evaluated by an Investigator to be clinically significant. A participant with abnormal vital signs results may be included in the study based on Investigator's judgment (e.g. a resting HR ≤ 45 in highly trained athletes);

20. Presence of any febrile illness (including an oral temperature [OT] ≥ 38.0 ˚C within 24 hours prior to vaccination;

21. 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;

22. Participants 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) of the Investigator or any employee of Medicago (or their family members);

23. Participants with a history of Guillain-Barré Syndrome.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medicago

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Medicago

Locations

(Site 225) Coastal Clinical Research

Mobile, Alabama, United States

(Site 201) Clinical Research Consortium

Tempe, Arizona, United States

(Site 213) Advanced Clinical Research

Banning, California, United States

(Site 246) Paradigm Clinical Research / Pharmaseek

Redding, California, United States

(Site 212) Benckmark Research

Sacramento, California, United States

(Site 244) Paradigm Clinical Research Center Inc

San Diego, California, United States

(Site 242) Paradigm Clinical Research Centers Inc

Wheat Ridge, Colorado, United States

(Site 239) Alliance for Multispeciality Research

Coral Gables, Florida, United States

(Site 222) Research Centers of America

Hollywood, Florida, United States

(Site 221) St-Johns Center for Clinical Research

Ponte Vedra, Florida, United States

(Site 231) QPS-MRA LLC

South Miami, Florida, United States

(Site 251) Meridian Clinical Research

Richmond Hill, Georgia, United States

(Site 240) Meridian Clinical Research LLC

Savannah, Georgia, United States

(Site 223) Clinical Research Atlanta

Stockbridge, Georgia, United States

(Site 249) Advanced Clinical Research

Meridian, Idaho, United States

(Site 219) Heartland Research Associates LLC

Augusta, Kansas, United States

(Site 234) Heartland Research Associates LLC

Newton, Kansas, United States

(Site 215) Heartland Research Associates LLC

Wichita, Kansas, United States

(Site 235) Heartland Research Associates LLC

Wichita, Kansas, United States

(Site 241) Central Kentucky Reserach Associates

Lexington, Kentucky, United States

(Site 203) Benchmark Research

Metairie, Louisiana, United States

(Site 227) Sundande Clinical Research

St Louis, Missouri, United States

(Site 226) Meridian Clinical Research LLC

Norfolk, Nebraska, United States

(Site 211) Meridian Clinical Research

Omaha, Nebraska, United States

(Site 209) United Medical Associates

Binghamton, New York, United States

(Site 217) Regional Clinical Research inc

Endwell, New York, United States

(Site 237) PMG Research of Cary LLC

Cary, North Carolina, United States

(Site 230) PMG Research of Charlotte LLC

Charlotte, North Carolina, United States

(Site 205) PMG Research of Rocky Mount LLC

Rocky Mount, North Carolina, United States

(Site 236) PMG Research

Statesville, North Carolina, United States

(Site 228) Research of Winston-Salem

Winston-Salem, North Carolina, United States

(Site 233) Sterling Research Group

Cincinnati, Ohio, United States

(Site 208) Sterling Research Group

Cincinnati, Ohio, United States

(Site 245) Rapid Medical Research

Cleveland, Ohio, United States

(Site 202) Aventiv Research Inc

Columbus, Ohio, United States

(Site 207) Lynn Institute of Norman

Norman, Oklahoma, United States

(Site 238) Tekton Research

Oklahoma City, Oklahoma, United States

(Site 216) PMG Research of Charleston LLC

Mt. Pleasant, South Carolina, United States

(Site 248) Coastal Carolina Research Center

Mt. Pleasant, South Carolina, United States

(Site 201) Meridian Clinical Research

Dakota Dunes, South Dakota, United States

(Site 247) New orleans Center for Clinical Research

Knoxville, Tennessee, United States

(Site 206) Benchmark Research

Austin, Texas, United States

(Site 218) Tekton Research Inc

Austin, Texas, United States

(Site 214) Ventavia Research Group LLC

Fort Worth, Texas, United States

(Site 224) Benchmark Research

Fort Worth, Texas, United States

(Site 232) Benchmark Research

San Angelo, Texas, United States

(Site 250) Clinical Trials of Texas Inc

San Antonio, Texas, United States

(Site 204) Jean Brown Research

Salt Lake City, Utah, United States

(Site 220) Advanced Clinical Research

West Jordan, Utah, United States

(Site 229) Clinical Research Associates of Tidewater

Norfolk, Virginia, United States

(Site 106) Colchester Research Group

Truro, Nova Scotia, Canada

(Site 113) Dawson Road Family Medical Clinic

Guelph, Ontario, Canada

(Site 110) Manna Research Inc.

Toronto, Ontario, Canada

(Site 103) Q & T Recherche Chicoutimi

Chicoutimi, Quebec, Canada

(Site 105) Q & T Outaouais

Gatineau, Quebec, Canada

(Site 107) Manna Research Inc.

Lévis, Quebec, Canada

(Site 109) Manna Research Inc. (Mirabel)

Mirabel, Quebec, Canada

(Site 108) Manna Research

Pointe-Claire, Quebec, Canada

(Site 102) CHU de Québec - Université Laval

Québec, Quebec, Canada

(site 101) Centre de Recherche St-Louis

Québec, Quebec, Canada

(Site 110) Alpha Recherche Clinique

Québec, Quebec, Canada

(Site 104) Q & T Recherche Sherbrooke

Sherbrooke, Quebec, Canada

(Site 112) Medexa Recherche

Victoriaville, Quebec, Canada

(Site 309) Espoo Vaccine Research Clinic

Espoo, , Finland

(Site 303) Helsinki South Vaccine Research Clinic

Helsinki, , Finland

(Site 308) Helsinki East Vaccine Research Center

Helsinki, , Finland

(Site 301) Jarvenpaa Vaccine Research Clinic

Järvenpää, , Finland

(Site 306) Kokkola Vaccine Research Clinic

Kokkola, , Finland

(Site 304) Oulu Vaccine Research Clinic

Oulu, , Finland

(Site 302) Tampere University Vaccine Research Center

Pori, , Finland

(Site 305) Seinaejoki Vaccine Research Clinic

Seinäjoki, , Finland

(Site 310) Tampere Vaccine Research Clinic

Tampere, , Finland

(Site 307) Turku Vaccine Research Center

Turku, , Finland

(Site 410) Emovis GmbH

Berlin, , Germany

(Site 418) Klinische Forschung Berlin GbR

Berlin, , Germany

(Site 422) Synexus Clinical Research GmbH

Berlin, , Germany

(Site 402) Synexus Clinical research GmbH

Bochum, , Germany

(Site 409) Gemeinschaftspraxis Dr. med Kleinecke-Pohl

Cologne, , Germany

(Site 401) Cardiologicum Dresden & Pirna

Dresden, , Germany

(Site 406) Diabetologische Germeinschafts praxis Faulman

Dresden, , Germany

(Site 405) Doktor Markus Faghih

Essen, , Germany

(Site 407) Klinisches Forschungszentrum Dr. Hagemann am Hausarztzer

Essen, , Germany

(Site 417) Medizentrum Essen-Borbeck

Essen, , Germany

(Site 414) Unterfrintroper Hausarztzentrum Klinische Forschung

Essen, , Germany

(SIte 404) Synexus Clinical Reserach GmbH

Frankfurt, , Germany

(Site 411) MedicoKIT GmbH

Goch, , Germany

(Site 425) Clinical Research Hamburg

Hamburg, , Germany

(Site 403) Praxis Dr. Med Cornelia Brauer

Hamburg, , Germany

(Site 408) Germeinsschaftspraxis Dr. med Christiane Klein/Minnich

Künzing, , Germany

(Site 421) SIBAmed Studienzentrum GmbH

Leipzig, , Germany

(Site 420) Synexus Clinical Research GmbH

Leipzig, , Germany

(Site 423) centrum fuer Diagnostik und Gesundheit

Munich, , Germany

(Site 413) Dr. Ingomar F.K. Naudts MD Office

Rodgau, , Germany

(Site 415) Praxisgemeinschaft Stuhr-Brinkum

Stuhr, , Germany

(Site 416) Praxis Dr. med Joachim Sauter

Wangen, , Germany

(Site 412) MALU-Medizinische Studien GmbH

Wardenburg, , Germany

(Site 424) Medislim GmbH

Weinheim, , Germany

(Site 603) Ramathibodi Hospital, Mahid - Division of Infectious Disease

Bangkok, , Thailand

(Site 606) Faculty of Tropical Medicine, Mahidol University

Bangkok, , Thailand

(Site 608) Phramongkutklao Hospital

Bangkok, , Thailand

(Site 609) Division of Tropical Pediatrics

Bangkok, , Thailand

(Site 601) Faculty of Medicine, Chiang Mai University

Chiang Mai, , Thailand

(Site 607) Srinagarind Hospital Khon Kaen University

Khon Kaen, , Thailand

(Site 605) Golden Jubilee Medical Center

Nakhon Pathom, , Thailand

Countries

United States; Canada; Finland; Germany; Thailand

References

Ward BJ, Makarkov A, Seguin A, Pillet S, Trepanier S, Dhaliwall J, Libman MD, Vesikari T, Landry N. Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18-64 years) and older adults (>/=65 years): two multicentre, randomised phase 3 trials. Lancet. 2020 Nov 7;396(10261):1491-1503. doi: 10.1016/S0140-6736(20)32014-6. Epub 2020 Oct 13.

Reference Type: RESULT

PMID: 33065035 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CP-PRO-QVLP-014

Identifier Type: -

Identifier Source: org_study_id