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

• ClinicalTrials.gov Identifier: NCT04636697
• Recruitment Status: Active, not recruiting
• First Posted: November 19, 2020
• Last Update Posted: April 6, 2022
• Sponsor: Medicago
• Information provided by (Responsible Party): Medicago

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
SARS-CoV-2 Infection	Drug: Intramuscular injection; Biological: Intramuscular vaccine	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30918 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Observer-blind
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: November 19, 2020
• Actual Primary Completion Date: August 25, 2021
• Estimated Study Completion Date: April 30, 2022

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Phase 2 portion: Immediate adverse event (AEs) [ Time Frame: 30 minutes ]
   Percentage, intensity, and relationship to vaccination of immediate AEs
2. Phase 2 portion: Solicited local and systemic adverse events (AEs) [ Time Frame: 7 days ]
   Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs
3. Phase 2 portion: Unsolicited adverse events (AEs) [ Time Frame: 21 days ]
   Percentage, intensity, and relationship of unsolicited AEs
4. Phase 2 portion: Number of subjects with normal and abnormal clinically significant urine values [ Time Frame: 3 days ]
   Number of subjects with normal and abnormal clinically significant urine values
5. Phase 2 portion: Number of subjects with normal and abnormal clinically significant haematological values [ Time Frame: 3 days ]
   Number of subjects with normal and abnormal clinically significant haematological values
6. Phase 2 portion: Number of subjects with normal and abnormal clinically significant biochemical values [ Time Frame: 3 days ]
   Number of subjects with normal and abnormal clinically significant biochemical values
7. Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant urine values [ Time Frame: 3 days ]
   Percentage of subjects with normal and abnormal clinically significant urine values
8. Phase 2 portion: Percentage of subjects with normal and abnormal clinically significant haematological values [ Time Frame: 3 days ]
   Percentage of subjects with normal and abnormal clinically significant haematological values
9. Phase 2 portion: Percentage of subjects with normal and abnormal clinically biochemical values [ Time Frame: 3 days ]
   Percentage of subjects with normal and abnormal clinically biochemical values
10. 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 [ Time Frame: 21 days ]
    Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths
11. Phase 2 portion: Neutralizing antibody (Nab assay) response [ Time Frame: Day 21 ]
    Nab response induced in each Study Population against the SARS-CoV-2 virus
12. Phase 2 portion: Neutralizing antibody (Nab assay) response [ Time Frame: Day 42 ]
    Nab response induced in each Study Population against the SARS-CoV-2 virus
13. Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 21 ]
    Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-γ ELISpot
14. Phase 2 portion:Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 42 ]
    Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 , as measured by IFN-γ ELISpot
15. Phase 3 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection [ Time Frame: Day 28 and after ]
    First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection

Secondary Outcome Measures :

1. Phase 2 portion: Solicited local and systemic AEs (populations 1 and 2) [ Time Frame: 7 days ]
   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);
2. Phase 2 portion: Solicited local and systemic AEs (populations 1, 2 and 3) [ Time Frame: 7 days ]
   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)
3. 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 [ Time Frame: Day 43 to 386 ]
   Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths
4. Phase 3 portion: Immediate adverse event (AEs) [ Time Frame: 30 minutes ]
   Percentage, intensity, and relationship to vaccination of immediate AEs
5. Phase 3 portion: Solicited local and systemic AEs [ Time Frame: 7 days ]
   Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs
6. Phase 3 portion: Unsolicited adverse events (AEs) [ Time Frame: 21 days ]
   Percentage, intensity, and relationship of unsolicited AEs
7. 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 [ Time Frame: Day 0 to 386 ]
   Percentage of SAEs, MAAEs, AEs leading to withdrawal, AESIs (including VED), and deaths
8. Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1 and 2) [ Time Frame: 21 days ]
   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)
9. Phase 2 portion: Neutralizing antibody Geometric mean tiers (GMT) response (populations 1, 2 and 3) [ Time Frame: 21 days ]
   • 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)
10. Phase 2 portion: Neutralizing antibody (Nab assay) response [ Time Frame: Day 128 ]
    Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus
11. Phase 2 portion: Neutralizing antibody (Nab assay) response [ Time Frame: Day 201 ]
    Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus
12. Phase 2 portion: Neutralizing antibody (Nab assay) response [ Time Frame: Day 386 ]
    Persistence of the Nab antibody response induced in each Study Population against the SARS-CoV-2 virus
13. Phase 2 portion: Specific antibody (IgG) response [ Time Frame: Day 128 ]
    Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels
14. Phase 2 portion: Specific antibody (IgG) response [ Time Frame: Day 201 ]
    Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels
15. Phase 2 portion: Specific antibody (IgG) response [ Time Frame: Day 386 ]
    Specific antibody response induced in each Study Population against the SARS-CoV-2 virus will be measured by the total IgG levels
16. Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 21 ]
    The ratio of neutralizing antibody titers:IgG ELISA antibody titers
17. Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 42 ]
    The ratio of neutralizing antibody titers:IgG ELISA antibody titers
18. Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 128 ]
    The ratio of neutralizing antibody titers:IgG ELISA antibody titers
19. Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 201 ]
    The ratio of neutralizing antibody titers:IgG ELISA antibody titers
20. Phase 2 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 386 ]
    The ratio of neutralizing antibody titers:IgG ELISA antibody titers
21. Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 201 ]
    Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot
22. Phase 2 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 386 ]
    Specific Th1 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IFN-γ ELISpot
23. Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 21 ]
    Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)
24. Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 42 ]
    Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)
25. Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 201 ]
    Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)
26. Phase 2 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 386 ]
    Specific Th2 CMI response induced in each Study Population against the SARS-CoV-2 virus; as measured by IL-4 (ELISpot)
27. Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response [ Time Frame: Day 21 ]
    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)
28. Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response [ Time Frame: Day 21 ]
    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
29. Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response [ Time Frame: Day 21 ]
    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)
30. Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response [ Time Frame: Day 42 ]
    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)
31. Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response [ Time Frame: Day 42 ]
    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
32. Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response [ Time Frame: Day 42 ]
    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)
33. Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response [ Time Frame: Day 201 ]
    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)
34. Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) [ Time Frame: Day 201 ]
    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)
35. Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response [ Time Frame: Day 201 ]
    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
36. Phase 3 portion: Neutralizing antibody Geometric mean fold rise (GMFR) response [ Time Frame: Day 386 ]
    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)
37. Phase 3 portion: Neutralizing antibody Geometric mean titers (GMT) response [ Time Frame: Day 386 ]
    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)
38. Phase 3 portion: Neutralizing antibody Seroconversion (SC) rate response [ Time Frame: Day 386 ]
    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
39. Phase 3 portion: Specific antibody (IgG) response [ Time Frame: Day 21 ]
    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
40. Phase 3 portion: Specific antibody (IgG) response [ Time Frame: Day 42 ]
    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
41. Phase 3 portion: Specific antibody (IgG) response [ Time Frame: Day 201 ]
    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
42. Phase 3 portion: Specific antibody (IgG) response [ Time Frame: Day 386 ]
    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
43. Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 21 ]
    In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers
44. Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 42 ]
    In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers
45. Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 201 ]
    In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers
46. Phase 3 portion: Neutralizing antibody titers: IgG ELISA antibody titers [ Time Frame: Day 386 ]
    In a subset of subjects, the ratio of neutralizing antibody titers:IgG ELISA antibody titers
47. Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 21 ]
    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
48. Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 42 ]
    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
49. Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 201 ]
    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
50. Phase 3 portion: Specific Th1 cell-mediated immunity (CMI) response [ Time Frame: Day 386 ]
    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
51. Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 21 ]
    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)
52. Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 42 ]
    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)
53. Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 201 ]
    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)
54. Phase 3 portion: Specific Th2 cell-mediated immunity (CMI) response [ Time Frame: Day 386 ]
    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)
55. Phase 2 portion: Laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection [ Time Frame: Day 28 to 386 ]
    First occurrence, in a subject, of laboratory-confirmed (virologic method) symptomatic SARS-CoV-2 infection
56. Phase 2 portion: Severe COVID-19 disease [ Time Frame: Day 28 to 386 ]
    Percentage of severe COVID-19 disease
57. Phase 3 portion: Severe COVID-19 disease [ Time Frame: Day 28 to 386 ]
    Percentage of severe COVID-19 disease
58. Phase 3 portion: COVID-19-related symptoms in virologically-confirmed cases [ Time Frame: through efficacy analysis, approximately 4 months ]
    Percentage and intensity of COVID-19-related symptoms
59. Phase 3 portion: Laboratory-confirmed asymptomatic SARS-CoV-2 infection [ Time Frame: Day 201 ]
    Percentage of laboratory-confirmed asymptomatic SARS-CoV-2 infection: confirmed by the ELISA method for the N protein
60. Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection [ Time Frame: through efficacy analysis, approximately 4 months ]
    First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method
61. Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection [ Time Frame: Day 0 to 21 ]
    First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method
62. Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection [ Time Frame: Day 21 to 28 ]
    First occurence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection: virologic method
63. Phase 3 portion: Viral shedding after SARS-CoV-2 infection [ Time Frame: through efficacy analysis, approximately 4 months ]
    Duration and intensity of viral shedding after SARS-CoV-2 infection
64. Phase 3 portion: Laboratory-confirmed symptomatic SARS-CoV-2 infection (by strain) [ Time Frame: through efficacy analysis, approximately 4 months ]
    First occurrence, in a subject, of laboratory-confirmed symptomatic SARS-CoV-2 infection by strain: virologic method

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Achieve Clinical Research, LLC dba Accel Research Sites

Birmingham, Alabama, United States, 35216

United States, Arizona

Fiel Family and Sports Medicine/CCT

Tempe, Arizona, United States, 85283

United States, California

Hope Clinical Research

Canoga Park, California, United States, 91303

CNS Network

Garden Grove, California, United States, 92845

Long Beach Clinical Trial Services Inc.

Long Beach, California, United States, 90806-3221

Pharmacology Research Institute

Newport Beach, California, United States, 92660

Wr-McCr, Llc

San Diego, California, United States, 92108

United States, District of Columbia

Ascension Providence Health System

Washington, District of Columbia, United States, 20017

United States, Florida

Alliance for Multispecialty Research

Coral Gables, Florida, United States, 33134-4321

Research Centers of America

Hollywood, Florida, United States, 33024

AppleMed Research Inc

Miami, Florida, United States, 33155

Elixia COVID-19

Palm Beach, Florida, United States, 33410

Precision Clinical Research

Sunrise, Florida, United States, 33351

United States, Georgia

Meridian Clinical Research

Savannah, Georgia, United States, 31406

United States, Idaho

ASR, LLC

Nampa, Idaho, United States, 83687

United States, Illinois

Affinity Health

Chicago, Illinois, United States, 60644

United States, Iowa

Meridian Clinical Research

Sioux City, Iowa, United States, 51106

United States, Louisiana

Benchmark Research

Covington, Louisiana, United States, 70433

United States, Michigan

Ascension St. John Vaccine Research Unit

Grosse Pointe Woods, Michigan, United States, 48236

United States, Nebraska

Methodist Physicians

Fremont, Nebraska, United States, 68130

Be Well Clinical Studies, LLC

Lincoln, Nebraska, United States, 68516

Meridian Clinical Research LLC

Norfolk, Nebraska, United States, 68701

Meridian Clinical Research LLC

Omaha, Nebraska, United States, 68134

United States, Nevada

Forte Family Practice/ CCT Research

Las Vegas, Nevada, United States, 89103

Excel Clinical Research

Las Vegas, Nevada, United States, 89109

Las Vegas Clinical Trials

North Las Vegas, Nevada, United States, 89030

United States, New Jersey

Hassman Research Institute

Berlin, New Jersey, United States, 08009

United States, New York

Meridian Clinical Research

Endwell, New York, United States, 13760

United States, North Carolina

Carolina Institute for Clinical Research

Fayetteville, North Carolina, United States, 28303

M3 Wake Research, Inc

Raleigh, North Carolina, United States, 27612

Trial Management Associates LLC

Wilmington, North Carolina, United States, 28403

United States, Ohio

Velocity Clinical Research - Cincinnati

Cincinnati, Ohio, United States, 45242

Velocity Clinical Research

Cleveland, Ohio, United States, 44122

Aventiv Research Inc

Columbus, Ohio, United States, 43213

United States, Rhode Island

Velocity Clinical Research Providence

Warwick, Rhode Island, United States, 02886

United States, Texas

Benchmark Research

Austin, Texas, United States, 78705

Tekton Research

Austin, Texas, United States, 78745

Global Medical Research

Dallas, Texas, United States, 75224

Benchmark Research

Fort Worth, Texas, United States, 76135

Research Your Health

Plano, Texas, United States, 75093

Mt. Olympus Medical Research, LLC

Sugar Land, Texas, United States, 77479

Sugar Lakes Family Practice

Sugar Land, Texas, United States, 77479

DM Clinical Research/Martin Diagnostic Clinic

Tomball, Texas, United States, 77375

United States, Utah

South Ogden Family Medicine

Ogden, Utah, United States, 84405

Advanced Clinical Research, Inc.

West Jordan, Utah, United States, 84088

Argentina

Mautalen Salud e Investigación (Expertia SA)

Buenos Aires, Argentina, C1128AAF

Fundación FunDaMos

Buenos Aires, Argentina, C1405BOA

Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich

Buenos Aires, Argentina, C1426

Sanatorio Allende

Córdoba, Argentina, 5000

Clinica Mayo de UMCB SRL

San Miguel De Tucumán, Argentina, T4000

Brazil

Instituto de Pesquisas Clinicas L2IP

Brasília, Brazil, 70200-730

Unidade Hospital do Rocio

Campo Largo, Brazil, 83606-177

Santa Casa De Misericordia De Belo Horizonte

Minas Gerais, Brazil, 30150-221

Centro de Pesquisa Clinica - Hospital Moinhos de Vento

Porto Alegre, Brazil, 90035-001

IBPClin Instituto Brasil de Pequisa Clinica

Rio De Janeiro, Brazil, 20241-180

Fundação Faculdade Regional de Medicina de Sao Jose do Rio Preto

São Paulo, Brazil, 15090-000

Azidus Brasil Pesquisa e Desenvolvimento Ltda

Valinhos, Brazil, 13271-130

Canada, Alberta

CARe Clinic

Red Deer, Alberta, Canada, T4N 6V7

Canada, Nova Scotia

IWK Health Centre- Dalhousie University-Canadian Center for Vaccinology

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Ontario

Aggarwal and Associates Ltd

Brampton, Ontario, Canada, L6T 0G1

Dawson Clinical Research Inc.

Guelph, Ontario, Canada, N1H 1B1

SKDS Research Inc.

Newmarket, Ontario, Canada, L3Y 5G8

LMC Clinical Research Inc. (CPU)

Toronto, Ontario, Canada, M4G 3E8

Manna Research Toronto

Toronto, Ontario, Canada, M9W 4L6

Canada, Quebec

Manna Research (Quebec)

Lévis, Quebec, Canada, G6W OM5

Manna Research (Mirabel)

Mirabel, Quebec, Canada, J7J 2K8

McGill University Health Centre Vaccine Study Centre

Pierrefonds, Quebec, Canada, H9H 4Y6

CHU de Québec-Université Laval

Québec City, Quebec, Canada, G1E 7G9

Diex Research Quebec Inc.

Québec, Quebec, Canada, G1N 4V3

Diex Recherche Joliette

Saint-Charles-Borromée, Quebec, Canada, J6E 2B4

Q&T Research Sherbrooke Inc.

Sherbrooke, Quebec, Canada, J1J 2G2

Diex Recherche Sherbrooke

Sherbrooke, Quebec, Canada, J1L 0H8

Mexico

Investigación Biomédica para el Desarrollo de Fármacos, S.A. de C.V.

Aguascalientes, Mexico, 20010

RM Pharma Specialists S.A. de C.V.

Ciudad de México, Mexico, 3100

Centro para el Desarrollo de la Medicina y de Asistencia Médica Especializada S.C.

Culiacán, Mexico, 80230

Centro Multidisciplinario para el Desarrollo Especializado de la Investigación Clínica en Yucatan S.C.P. (CEMDEICY S.C.P.)

Mérida, Mexico, 97130

Integra RGH Centro de Investigacion, Clinica de Ozonoterapia RGH AC

Puebla, Mexico, 72410

Sociedad de Metabolismo y Corazon S.C (SOMECO)

Veracruz, Mexico, 91900

Investigación Biomédica para el Desarrollo de Fármacos, S.A. de C.V.

Zapopan, Mexico, 45070

United Kingdom

NHS Grampian

Aberdeen, United Kingdom, AB25 2ZD

Synexus Midlands Clinical Research Centre

Birmingham, United Kingdom, B15 2SQ

University Hospital Southampton NHS Foundation Trust (UHS)

Bournemouth, United Kingdom, BH7 7DW

Public Health Wales

Cardiff, United Kingdom, CF10 4BZ

Synexus Wales DRS

Cardiff, United Kingdom, CF15 9SS

Mid and South Essex NHS Foundation Trust

Chelmsford, United Kingdom, CM17ET

Synexus Lancashire DRS

Chorley, United Kingdom, PR7 7 NA

University Hospitals Derby and Burton

Derby, United Kingdom, DE22 3NE

London North West University Healthcare NHS Trust

Harrow, United Kingdom, HA1 3UJ

Kings College Hospital

London, United Kingdom, SE5 9PJ

Synexus Manchester DRS

Manchester, United Kingdom, M15 6SE

University of York/York Teaching Hospital

York, United Kingdom, YO31 8HE

Sponsors and Collaborators

Medicago

Investigators

• Study Director: Brian Ward, MD; Medicago

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Medicago
• ClinicalTrials.gov Identifier: NCT04636697
• Obsolete Identifiers: NCT04662697
• Other Study ID Numbers: CP-PRO-CoVLP-021
• First Posted: November 19, 2020
• Last Update Posted: April 6, 2022
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Pneumonia, Viral; Pneumonia; Lung Diseases; Respiratory Tract Diseases