Study of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults

Randomized, Observer-Blind, Placebo-Controlled, Phase 2/3 Study to Assess the Safety, Efficacy, and Immunogenicity of a Recombinant Coronavirus-Like Particle COVID-19 Vaccine in Adults 18 Years of Age or Older

This Phase 2/3 study is a multi-portion design to confirm that the chosen formulation and dosing regimen of CoVLP has an acceptable immunogenicity and safety profile.

The Phase 3 portion is an event-driven, randomized, observer blinded, placebo-controlled design that will evaluate the efficacy and safety of the CoVLP formulation compared to placebo.

Subjects will be followed for safety and immunogenicity for a period of 12 months after the last vaccination.

Study Overview

• Status: Active, not recruiting
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Drug: Intramuscular injection; Biological: Intramuscular vaccine

• Study Type: Interventional
• Enrollment (Anticipated): 30918
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1128AAF
    • Mautalen Salud e Investigación (Expertia SA)
  • Buenos Aires, Argentina, C1405BOA
    • Fundación FunDaMos
  • Buenos Aires, Argentina, C1426
    • Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich
  • Córdoba, Argentina, 5000
    • Sanatorio Allende
  • San Miguel De Tucumán, Argentina, T4000
    • Clinica Mayo de UMCB SRL
• Brazil
  • Brasília, Brazil, 70200-730
    • Instituto de Pesquisas Clinicas L2IP
  • Campo Largo, Brazil, 83606-177
    • Unidade Hospital do Rocio
  • Minas Gerais, Brazil, 30150-221
    • Santa Casa de Misericórdia de Belo Horizonte
  • Porto Alegre, Brazil, 90035-001
    • Centro de Pesquisa Clinica - Hospital Moinhos de Vento
  • Rio De Janeiro, Brazil, 20241-180
    • IBPClin Instituto Brasil de Pequisa Clinica
  • São Paulo, Brazil, 15090-000
    • Fundação Faculdade Regional de Medicina de São José do Rio Preto
  • Valinhos, Brazil, 13271-130
    • Azidus Brasil Pesquisa e Desenvolvimento Ltda
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4N 6V7
      • CARe Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • IWK Health Centre- Dalhousie University-Canadian Center for Vaccinology
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and associates Ltd
    • Guelph, Ontario, Canada, N1H 1B1
      • Dawson Clinical Research Inc.
    • Newmarket, Ontario, Canada, L3Y 5G8
      • SKDS Research Inc.
    • Toronto, Ontario, Canada, M9W 4L6
      • Manna Research Toronto
    • Toronto, Ontario, Canada, M4G 3E8
      • LMC Clinical Research Inc. (CPU)
  • Quebec
    • Lévis, Quebec, Canada, G6W OM5
      • Manna Research (Quebec)
    • Mirabel, Quebec, Canada, J7J 2K8
      • Manna Research (Mirabel)
    • Pierrefonds, Quebec, Canada, H9H 4Y6
      • McGill University Health Centre Vaccine Study Centre
    • Québec, Quebec, Canada, G1N 4V3
      • DIEX Research Quebec Inc.
    • Québec City, Quebec, Canada, G1E 7G9
      • CHU de Quebec-Universite Laval
    • Saint-Charles-Borromée, Quebec, Canada, J6E 2B4
      • Diex Recherche Joliette
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Q&T Research Sherbrooke Inc.
    • Sherbrooke, Quebec, Canada, J1L 0H8
      • Diex Recherche Sherbrooke
• Mexico
  • Aguascalientes, Mexico, 20010
    • Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de C.V.
  • Ciudad de México, Mexico, 3100
    • RM Pharma Specialists S.A. de C.V.
  • Culiacán, Mexico, 80230
    • Centro Para El Desarrollo de La Medicina Y de Asistencia Medica Especializada S.C.
  • Mérida, Mexico, 97130
    • Centro Multidisciplinario Para El Desarrollo Especializado De La Investigación Clínica En Yucatán S.C.P. (CEMDEICY S.C.P.)
  • Puebla, Mexico, 72410
    • Integra RGH Centro de Investigacion, Clinica de Ozonoterapia RGH AC
  • Veracruz, Mexico, 91900
    • Sociedad de Metabolismo y Corazon S.C (SOMECO)
  • Zapopan, Mexico, 45070
    • Investigacion Biomedica para el Desarrollo de Farmacos, S.A. de C.V.
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZD
    • NHS Grampian
  • Birmingham, United Kingdom, B15 2SQ
    • Synexus Midlands Clinical Research Centre
  • Bournemouth, United Kingdom, BH7 7DW
    • University Hospital Southampton NHS Foundation Trust (UHS)
  • Cardiff, United Kingdom, CF10 4BZ
    • Public Health Wales
  • Cardiff, United Kingdom, CF15 9SS
    • Synexus Wales DRS
  • Chelmsford, United Kingdom, CM17ET
    • Mid and South Essex Nhs Foundation Trust
  • Chorley, United Kingdom, PR7 7 NA
    • Synexus Lancashire DRS
  • Derby, United Kingdom, DE22 3NE
    • University Hospitals Derby and Burton
  • Harrow, United Kingdom, HA1 3UJ
    • London North West University Healthcare NHS Trust
  • London, United Kingdom, SE5 9PJ
    • Kings College Hospital
  • Manchester, United Kingdom, M15 6SE
    • Synexus Manchester DRS
  • York, United Kingdom, YO31 8HE
    • University of York/York Teaching Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC dba Accel Research Sites
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Fiel Family and Sports Medicine/CCT
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Garden Grove, California, United States, 92845
      • CNS Network
    • Long Beach, California, United States, 90806-3221
      • Long Beach Clinical Trial Services Inc.
    • Newport Beach, California, United States, 92660
      • Pharmacology Research Institute
    • San Diego, California, United States, 92108
      • Wr-McCr, Llc
  • District of Columbia
    • Washington, District of Columbia, United States, 20017
      • Ascension Providence Health System
  • Florida
    • Coral Gables, Florida, United States, 33134-4321
      • Alliance for Multispecialty Research
    • Hollywood, Florida, United States, 33024
      • Research Centers of America
    • Miami, Florida, United States, 33155
      • AppleMed Research Inc
    • Palm Beach, Florida, United States, 33410
      • Elixia COVID-19
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
  • Idaho
    • Nampa, Idaho, United States, 83687
      • ASR, LLC
  • Illinois
    • Chicago, Illinois, United States, 60644
      • Affinity Health
  • Iowa
    • Sioux City, Iowa, United States, 51106
      • Meridian Clinical Research
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Benchmark Research
  • Michigan
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Ascension St. John Vaccine Research Unit
  • Nebraska
    • Fremont, Nebraska, United States, 68130
      • Methodist Physicians
    • Lincoln, Nebraska, United States, 68516
      • Be Well Clinical Studies, LLC
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research LLC
    • Omaha, Nebraska, United States, 68134
      • Meridian Clinical Research LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89103
      • Forte Family Practice/ CCT Research
    • North Las Vegas, Nevada, United States, 89030
      • Las Vegas Clinical Trials
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • New York
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research
  • North Carolina
    • Fayetteville, North Carolina, United States, 28303
      • Carolina Institute for Clinical Research
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Velocity Clinical Research - Cincinnati
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research
    • Columbus, Ohio, United States, 43213
      • Aventiv Research Inc
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Velocity Clinical Research Providence
  • Texas
    • Austin, Texas, United States, 78705
      • Benchmark Research
    • Austin, Texas, United States, 78745
      • Tekton Research
    • Dallas, Texas, United States, 75224
      • Global Medical Research
    • Fort Worth, Texas, United States, 76135
      • Benchmark Research
    • Plano, Texas, United States, 75093
      • Research Your Health
    • Sugar Land, Texas, United States, 77479
      • Sugar Lakes Family Practice
    • Sugar Land, Texas, United States, 77479
      • Mt. Olympus Medical Research, LLC
    • Tomball, Texas, United States, 77375
      • DM Clinical Research/Martin Diagnostic Clinic
  • Utah
    • Ogden, Utah, United States, 84405
      • South Ogden Family Medicine
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

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

2. At the Screening visit (Visit 1), male and female subjects must be:

   • Study Populations #1: 18 to 64 (has not yet had his/her 65th birthday) years of age, inclusive;
   • Study Population #2: 65 years of age or older;
   • Study Population #3: 18 years of age or older;

3. At Screening (Visit 1) and Vaccination (Visit 2), subject must have a body mass index (BMI) of:

   • Study Populations #1 and #2: ≥ 18.5 and < 30 kg/m2;

4. 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;

5. Study Population #1: 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 determined by medical history, physical examination, and vital signs. Investigator discretion will be permitted with this inclusion criterion;

   All regions except Canada: 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 that must be documented in the source documents, 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. Study Populations #1 and #3: Female subjects of childbearing potential must have a negative serum pregnancy test result at Screening (Visit 1 for the Phase 2 portion) and/or a negative urine pregnancy test result at Vaccination (Visit 2 for the Phase 2 portion; Visit 1 for the Phase 3 portion):

   Non-childbearing females are defined as:

   • Surgically-sterile (defined as bilateral tubal ligation, hysterectomy or bilateral oophorectomy performed more than one month prior to the first study vaccination); or
   • Post-menopausal (absence of menses for 12 consecutive months and age consistent with natural cessation of ovulation);

7. Study Populations #1 and #3: Female subjects of childbearing potential must use an effective method of contraception for one month prior to vaccination (Visit 2) and agree to continue employing highly effective birth control measures for at least one month after the last study vaccination (or in the case of early termination, she must not plan to become pregnant for at least one month after her last study vaccination).

   The following relationship or methods of contraception are considered to be highly effective:

   • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
   • Oral;
   • Intravaginal;
   • Transdermal;
   • Progestogen-only hormonal contraception associated with inhibition of ovulation:
   • Oral;
   • Injectable;
   • Implantable;
   • Intra-uterine device with or without hormonal release;
   • Credible self-reported history of heterosexual vaginal intercourse abstinence prior to and for at least one month after the last study vaccination. Abstinent subjects who are ovulating should be asked what method(s) they would use should their circumstances change, and subjects without a well-defined plan should be excluded;
   • Female partner;
   • All regions except the US: Vasectomised partner, provided that this partner is the sole sexual partner of the study participant and that the vasectomised partner has received a medical assessment of the surgical success;
   • Bilateral tubal ligation.

8. Study Population #2: Subjects 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 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, serology (only for the Phase 2 portion), clinical chemistry and haematology tests (only for the Phase 2 portion), urinalysis (only for the Phase 2 portion), and vital signs. Investigator discretion will be permitted with this inclusion criterion.

   All regions except Canada: 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 that must be documented in the source documents, 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 and documented in source documentation, a subject with more recent stabilization of a disease could also be eligible;

9. Study Population #3: Subjects must have one or more co-morbid conditions that puts them at higher risk for severe COVID-19 disease. These comorbidities include but are not limited to obesity, hypertension, type 1 or type 2 diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular diseases, chronic kidney diseases, or be immunocompromised persons (e.g., treatment-controlled HIV infection, organ transplant recipients, or patients receiving cancer chemotherapy). Investigator discretion will be permitted with this inclusion criterion.

Exclusion criteria:

1. Study Populations #1 and #2: According to the Investigator's opinion, significant acute or chronic, uncontrolled medical or neuropsychiatric illness.

   Acute disease is defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening (Visit 1) and/or Vaccination visit (Visit 2). 'Uncontrolled' is defined as:

   • Requiring a new medical or surgical treatment during the three months prior to study vaccine administration;
   • 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 (Study Population #1) or no. 8 (Study Population #2) and is appropriately justified and documented by the Investigator.

   Investigator discretion is permitted with this exclusion criterion and must be carefully and fully documented in the source documents;

2. Study Populations #1 and #2: Any chronic medical condition associated with elevated risk of severe outcomes of COVID-19, including obesity, diabetes (type 1 or type 2), significant cardiovascular or respiratory diseases including asthma, chronic renal failure, disorders of bleeding/coagulation, chronic inflammatory or autoimmune conditions, immunosuppressive conditions (including HIV), and hypertension;
3. Study Populations #1 and #2: Any confirmed or suspected current immunosuppressive condition or immunodeficiency, including cancer, human immunodeficiency virus (HIV), hepatitis B or C infection (subjects with a history of cured hepatitis B or C infection without any signs of immunodeficiency at present time are allowed). Investigator discretion is permitted with this exclusion criterion;
4. Study Populations #1 and #2: Current autoimmune disease (such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis or narcolepsy). Investigator discretion is permitted with this exclusion criterion, and subjects may be eligible to participate with appropriate written justification in the source document (i.e. subjects with a history of autoimmune disease who are disease-free without treatment for three years or more, or on stable thyroid replacement therapy, mild psoriasis [i.e. a small number of minor plaques requiring no systemic treatment], etc.);

5. Study Populations #1 and #2: Administration of any medication or treatment that may alter the vaccine immune responses, such as:

   • 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 prior to the Vaccination visit (Visit 2). Inhaled, nasal, ophthalmic, dermatological, and other topical glucocorticoids are permitted;
   • Cytotoxic, antineoplastic, or immunosuppressant drugs - within 36 months prior to Vaccination (Visit 2);
   • Any immunoglobulin preparations or blood products, blood transfusion - within 6 months prior to Vaccination (Visit 2);
6. Study Population #3: Acute disease defined as presence of any moderate or severe acute illness with or without a fever within 48 hours prior to the Screening (Visit 1) and/or Vaccination visit (Visit 2);
7. Administration of any vaccine within 14 days prior to Vaccination (Visit 2); planned administration of any vaccine during the study (up to Day 28 of the study). Immunization on an emergency basis during the study will be evaluated on case-by-case basis by the Investigator;
8. Administration of any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study;
9. History of virologically-confirmed COVID-19;
10. Use of any investigational or non-registered product within 30 days or 5 half-lives, whichever is longer, prior to Vaccination (Visit 2) or planned use during the study period. Subjects who are in a prolonged post-administration observation period of another investigational or marketed drug clinical study, for which there is no ongoing exposure to the investigational or marketed product and all scheduled on-site visits are completed, will be allowed to take part in this study, if all other eligibility criteria are met;
11. Have a rash, dermatological condition, tattoos, muscle mass, or any other abnormalities at injection site that may interfere with injection site reaction rating. Investigator discretion will be permitted with this exclusion criterion;
12. Use of any prescription antiviral drugs with the intention of COVID-19 prophylaxis, including those that are thought to be effective for prevention of COVID-19 but have not been licensed for this indication, within one month prior to Vaccination (Visit 2);
13. For the Phase 2 portion of the study only: Use of prophylactic medications (e.g. antihistamines [H1 receptor antagonists], nonsteroidal anti-inflammatory drugs [NSAIDs], systemic and topical glucocorticoids, non-opioid and opioid analgesics) within 24 hours prior to the Vaccination (Visit 2) to prevent or pre-empt symptoms due to vaccination;
14. History of a serious allergic response to any of the constituents of CoVLP including AS03;
15. History of a documented anaphylactic reactions to plants or plant components (including tobacco, fruits and nuts);
16. Personal or family history of narcolepsy;
17. Subjects with a history of Guillain-Barré Syndrome;
18. Study Populations #1 and #3: Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;
19. 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 employees of Medicago.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo (0.5 mL)	Drug: Intramuscular injection; Subjects will receive two doses of placebo given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)
Experimental: 3.75 µg of CoVLP Vaccine adjuvanted; 3.75 µg of CoVLP adjuvanted vaccine with AS03 adjuvant (0.5 mL)	Biological: Intramuscular vaccine; Subjects will receive two doses of 3.75 µg of CoVLP adjuvanted with AS03 adjuvant given 21 days apart into the deltoid region of the alternating arm (each arm will be injected once)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2 portion: Immediate adverse event (AEs)	Percentage, intensity, and relationship to vaccination of immediate AEs	30 minutes
Phase 2 portion: Solicited local and systemic adverse events (AEs)	Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs	7 days
Phase 2 portion: Unsolicited adverse events (AEs)	Percentage, intensity, and relationship of unsolicited AEs	21 days
Phase 2 portion: Number of subjects with normal and abnormal clinically significant urine values	Number of subjects with normal and abnormal clinically significant urine values	3 days
Phase 2 portion: Number of subjects with normal and abnormal clinically significant haematological values	Number of subjects with normal and abnormal clinically significant haematological values	3 days
Phase 2 portion: Number of subjects with normal and abnormal clinically significant biochemical values	Number of subjects with normal and abnormal clinically significant biochemical values	3 days
Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant urine values	Percentage of subjects with normal and abnormal clinically significant urine values	3 days
Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant haematological values	Percentage of subjects with normal and abnormal clinically significant haematological values	3 days
Phase 2 portion: Percentage of subjects with normal and abnormal clinically biochemical values	Percentage of subjects with normal and abnormal clinically biochemical values	3 days
Phase 2 portion: Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	21 days
Phase 2 portion: Neutralizing antibody (Nab assay) response	Nab response induced in each Study Population against the SARS-CoV-2 virus	Day 21
Phase 2 portion: Neutralizing antibody (Nab assay) response	Nab response induced in each Study Population against the SARS-CoV-2 virus	Day 42
Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-γ ELISpot	Day 21
Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-γ ELISpot	Day 42
Phase 3 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	Day 28 and after

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2 portion: Solicited local and systemic AEs (populations 1 and 2)	Relative percentage of solicited local and systemic AEs following each vaccine administration between the healthy adults (Study Population #1) and the healthy elderly population (Study Population #2, each age strata);	7 days
Phase 2 portion: Solicited local and systemic AEs (populations 1, 2 and 3)	Relative percentage of solicited local and systemic AEs by intensity grades for seven days following each vaccine administration between the healthy adults (Study Population #1) and the healthy elderly adults (Study Population #2) combined and the adults with significant comorbidities (Study Population #3)	7 days
Phase 2 portion: Serious adverse events (SAEs), medically attended adverse events (MAAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	Day 43 to 386
Phase 3 portion: Immediate adverse event (AEs)	Percentage, intensity, and relationship to vaccination of immediate AEs	30 minutes
Phase 3 portion: Solicited local and systemic AEs	Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs	7 days
Phase 3 portion: Unsolicited adverse events (AEs)	Percentage, intensity, and relationship of unsolicited AEs	21 days
Phase 3 portion: Serious adverse events (SAEs), adverse events (AEs) leading to withdrawal, adverse event of special interest (AESI) (including vaccine-enhanced disease) and deaths	Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths	Day 0 to 386
Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1 and 2)	Relative neutralizing antibody response between the healthy adults (Study Population #1) and the healthy elderly population (Study Population #2; each age strata) will be analyzed using the Following parameter: Geometric mean tiers (GMT)	21 days
Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1, 2 and 3)	• Relative neutralizing antibody response between the healthy adults (Study Population #1) and the healthy elderly adults (Study Population #2) combined and the adults with significant comorbidities (Study Population #3) will be analyzed using the Following parameter: Geometric mean tiers (GMT)	21 days
Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 128
Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 201
Phase 2 portion: Neutralizing antibody (Nab assay) response	Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus	Day 386
Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 128
Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 201
Phase 2 portion: Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels	Day 386
Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 21
Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 42
Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 128
Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 201
Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 386
Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 201
Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response	Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 386
Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 21
Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 42
Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 201
Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response	Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 386
Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 21
Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 21
Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 21
Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 42
Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 42
Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 42
Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 201
Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT)	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 201
Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 201
Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 386
Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 386
Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response	In a subset of subjects, Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 386
Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 21
Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 42
Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 201
Phase 3 portion: Specific antibody (IgG) response	In a subset of subjects, specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 386
Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 21
Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 42
Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 201
Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers	In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 386
Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 21
Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 42
Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 201
Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot	Day 386
Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 21
Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 42
Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 201
Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response	In a subset of subjects, specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)	Day 386
Phase 2 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection	Day 28 to 386
Phase 2 portion: Severe COVID-19 disease	Percentage of severe COVID-19 disease	Day 28 to 386
Phase 3 portion: Severe COVID-19 disease	Percentage of severe COVID-19 disease	Day 28 to 386
Phase 3 portion: COVID-19-related symptoms in virologically-confirmed cases	Percentage and intensity of COVID-19-related symptoms	through efficacy analysis, approximately 4 months
Phase 3 portion: Laboratory-confirmed asymptomatic SARS-CoV-2 infection	Percentage of laboratory-confirmed asymptomatic SARS-CoV-2 infection: confirmed by the ELISA method for the N protein	Day 201
Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	through efficacy analysis, approximately 4 months
Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	Day 0 to 21
Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection	First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method	Day 21 to 28
Phase 3 portion: Viral shedding after SARS-CoV-2 infection	Duration and intensity of viral shedding after SARS-CoV-2 infection	through efficacy analysis, approximately 4 months
Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection (by strain)	First occurrence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection by strain: virologic method	through efficacy analysis, approximately 4 months

Collaborators and Investigators

• Sponsor: Medicago
• Investigators: Study Director: Brian Ward, MD, Medicago

Publications and helpful links

General Publications

• Hager KJ, Perez Marc G, Gobeil P, Diaz RS, Heizer G, Llapur C, Makarkov AI, Vasconcellos E, Pillet S, Riera F, Saxena P, Geller Wolff P, Bhutada K, Wallace G, Aazami H, Jones CE, Polack FP, Ferrara L, Atkins J, Boulay I, Dhaliwall J, Charland N, Couture MMJ, Jiang-Wright J, Landry N, Lapointe S, Lorin A, Mahmood A, Moulton LH, Pahmer E, Parent J, Seguin A, Tran L, Breuer T, Ceregido MA, Koutsoukos M, Roman F, Namba J, D'Aoust MA, Trepanier S, Kimura Y, Ward BJ; CoVLP Study Team. Efficacy and Safety of a Recombinant Plant-Based Adjuvanted Covid-19 Vaccine. N Engl J Med. 2022 Jun 2;386(22):2084-2096. doi: 10.1056/NEJMoa2201300. Epub 2022 May 4.

Helpful Links

• To obtain contact information for a study center near you, click here

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2020
• Primary Completion (Actual): August 25, 2021
• Study Completion (Anticipated): April 30, 2022

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: November 18, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CP-PRO-CoVLP-021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No