Resumen

Este estudio de fase 2/3 presenta un diseño de múltiples partes para confirmar que la formulación y el régimen de dosificación elegidos de CoVLP tienen un perfil de inmunogenicidad y seguridad aceptable. La parte de fase 3 es un diseño basado en eventos, aleatorizado, con enmascaramiento del observador y controlado con placebo, que evaluará la eficacia y seguridad de la formulación CoVLP en comparación con placebo. Los sujetos serán seguidos en cuanto a seguridad e inmunogenicidad durante un período de 12 meses después de la última vacunación.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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;
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;
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;
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;
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.
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);
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.
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;
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.

Criterios de exclusión

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;
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;
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;
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.);
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);
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);
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;
Administration of any other SARS-CoV-2 / COVID-19, or other experimental coronavirus vaccine at any time prior to or during the study;
History of virologically-confirmed COVID-19;
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;
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;
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);
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;
History of a serious allergic response to any of the constituents of CoVLP including AS03;
History of a documented anaphylactic reactions to plants or plant components (including tobacco, fruits and nuts);
Personal or family history of narcolepsy;
Subjects with a history of Guillain-Barré Syndrome;
Study Populations #1 and #3: Any female subject who has a positive or doubtful pregnancy test result prior to vaccination or who is lactating;
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.

Intervenciones

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 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)

Estudio aleatorizado, con enmascaramiento del observador, controlado con placebo, de fase 2/3, para evaluar la seguridad, eficacia e inmunogenicidad de una vacuna recombinante contra la COVID-19 similar a partículas de coronavirus en adultos de 18 años o más

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Intramuscular injection

Intramuscular vaccine

Ubicaciones

Mautalen Salud e Investigación (Expertia SA)

Fundación FunDaMos

Hospital Militar Central Cirujano Mayor Dr. Cosme Argerich

Sanatorio Allende

Clinica Mayo de UMCB SRL

Patrocinadores