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

SARS-CoV-2 Infection Clinical Trial

Official title:

A Randomized, Observer-Blind, Placebo-Controlled 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 (United States - Phase 2)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04662697
• Other study ID #: CP-PRO-CoVLP-021(USA)
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 11, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: December 2020
• Source: Medicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This Phase 2 study design will confirm that the chosen formulation and dosing regimen of CoVLP has an acceptable immunogenicity and safety profile. Subjects will be followed for durability of the immune responses for a period of 12 months after the last vaccination.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 918
• Est. completion date: March 31, 2022
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Populations #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; 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) and a negative urine pregnancy test result at Vaccination (Visit 2):

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), with the exception of the following subjects: 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.

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, clinical chemistry and haematology tests, urinalysis, and vital signs. Investigator discretion will be permitted with this inclusion criterion. 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 co-morbidities include but are not limited to obesity, documented hypertension, type-1 or type 2 diabetes, chronic obstructive lung diseases (COPD), cardiovascular disease, chronic kidney, or be immunocompromised persons (e.g., HIV-infected patients, 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 I/II), significant cardiovascular or respiratory disease 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. 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;

10. 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;

11. 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);

12. 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;

13. History of a serious allergic response to any of the constituents of CoVLP including AS03;

14. History of a documented anaphylactic reactions to plants or plant components (including tobacco, fruits and nuts);

15. Family history of narcolepsy;

16. Subjects with a history of Guillain-Barré Syndrome;

17. Study Populations #1 and #3: Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;

18. 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

Related Conditions & MeSH terms

• Coronavirus Infections
• SARS-CoV-2 Infection

Intervention

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)

Biological:
• intramuscular accine
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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Medicago

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immediate adverse event (AEs)	Percentage, intensity, and relationship to vaccination of immediate AEs	30 minutes
Primary	Solicited local and systemic adverse events (AEs)	Percentage, intensity, and relationship to vaccination of solicited local and systemic AEs	7 days
Primary	Unsolicited adverse events (AEs)	Percentage, intensity, and relationship of unsolicited AEs	21 days
Primary	Number of subjects with normal and abnormal clinically significant urine values	Number of subjects with normal and abnormal clinically significant urine values	3 days
Primary	Percentage of subjects with normal and abnormal clinically significant urine values	Percentage of subjects with normal and abnormal clinically significant urine values	3 days
Primary	Number of subjects with normal and abnormal clinically significant haematological values	Number of subjects with normal and abnormal clinically significant haematological values	3 days
Primary	Percentage of subjects with normal and abnormal clinically significant haematological values	Percentage of subjects with normal and abnormal clinically significant haematological values	3 days
Primary	Number of subjects with normal and abnormal clinically significant biochemical values	Number of subjects with normal and abnormal clinically significant biochemical values	3 days
Primary	Percentage of subjects with normal and abnormal clinically significant biochemical values	Percentage of subjects with normal and abnormal clinically significant biochemical values	3 days
Primary	Serious adverse events (SAEs), Medically attended adverse event (MAAE), 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
Primary	Neutralizing antibody Geometric mean titers (GMT) response	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
Primary	Neutralizing antibody Geometric mean titers (GMT) response	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
Primary	Neutralizing antibody Seroconversion (SC) rate response	Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 21
Primary	Neutralizing antibody Seroconversion (SC) rate response	Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 42
Primary	Neutralizing antibody Geometric mean fold rise (GMFR) response	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
Primary	Neutralizing antibody Geometric mean fold rise (GMFR) response	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
Primary	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-? ELISpot	Day 21
Primary	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-? ELISpot	Day 42
Secondary	Serious adverse events (SAEs), Medically attended adverse event (MAAE), 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
Secondary	Neutralizing antibody Geometric mean titers (GMT) response	Persistence of Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 128
Secondary	Neutralizing antibody Geometric mean titers (GMT) response	Persistence of 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
Secondary	Neutralizing antibody Geometric mean titers (GMT) response	Persistence of 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
Secondary	Neutralizing antibody Seroconversion (SC) rate response	Persistence of Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 128
Secondary	Neutralizing antibody Seroconversion (SC) rate response	Persistence of Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 201
Secondary	Neutralizing antibody Seroconversion (SC) rate response	Persistence of Nab antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 386
Secondary	Neutralizing antibody Geometric mean fold rise (GMFR) response	Persistence of 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 128
Secondary	Neutralizing antibody Geometric mean fold rise (GMFR) response	Persistence of 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
Secondary	Neutralizing antibody Geometric mean fold rise (GMFR) response	Persistence of 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
Secondary	Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 21
Secondary	Specific antibody (IgG) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus measured by the total IgG levels	Day 42
Secondary	Specific antibody Geometric mean titers (GMT) response	Specific antibody response CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 128
Secondary	Specific antibody Geometric mean titers (GMT) response	Specific antibody response CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 201
Secondary	Specific antibody Geometric mean titers (GMT) response	Specific antibody response CoV-2 virus analyzed, using the following parameters: Geometric mean titers (GMT)	Day 386
Secondary	Specific antibody Seroconversion (SC) rate response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 128
Secondary	Specific antibody Seroconversion (SC) rate response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 201
Secondary	Specific antibody Seroconversion (SC) rate response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Seroconversion (SC) rate	Day 386
Secondary	Specific antibody Geometric mean fold rise (GMFR) response	Specific antibody response induced in each Study Population against the SARS-CoV-2 virus analyzed, using the following parameters: Geometric mean fold rise (GMFR)	Day 128
Secondary	Specific antibody Geometric mean fold rise (GMFR) response	Specific 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
Secondary	Specific antibody Geometric mean fold rise (GMFR) response	Specific 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
Secondary	Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 21
Secondary	Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 42
Secondary	Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 128
Secondary	Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 201
Secondary	Neutralizing antibody titers: IgG ELISA antibody titers	The ratio of neutralizing antibody titers:IgG ELISA antibody titers	Day 386
Secondary	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-? ELISpot	Day 201
Secondary	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-? ELISpot	Day 386
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Laboratory-confirmed asymptomatic SARS-CoV-2 infection	Percentage of laboratory-confirmed (confirmed by the ELISA method for the N protein) asymptomatic SARS-CoV-2 infection	Day 35 to 386
Secondary	Severe COVID-19 disease	Percentage of severe COVID-19 disease	Day 35 to 386