|E.1 Medical condition or disease under investigation |
|E.1.1||Medical condition(s) being investigated || |
|E.1.1.1||Medical condition in easily understood language || |
|E.1.1.2||Therapeutic area ||Diseases [C] - Virus Diseases [C02] |
|MedDRA Classification |
|E.1.2 Medical condition or disease under investigation |
|E.1.2||Version ||23.1 |
|E.1.2||Level ||PT |
|E.1.2||Classification code ||10084457 |
|E.1.2||Term ||COVID-19 immunisation |
|E.1.2||System Organ Class ||10042613 - Surgical and medical procedures |
|E.1.3||Condition being studied is a rare disease || No |
|E.2 Objective of the trial |
|E.2.1||Main objective of the trial || |
|The primary objective of this phase 3 trial is to assess the non-inferiority, or superiority of vaccination with ABNCoV2 compared to Comirnaty in terms of neutralizing antibodies against the SARS CoV 2 index virus (Wuhan wild type isolate). This objective will be carried out in the randomized, double-blind component (Part A), in Cohort 1 (adult subjects who previously completed primary vaccination only) and Cohort 2 (adult subjects who have received 1 booster vaccination after a primary regimen) simultaneously. If the non-inferiority margin is met, superiority comparison will be carried out in the same cohort with the same type I error level. If for any reason, the minimum sample size of 400 is not met in one cohort, data from that cohort will be summarized descriptively. |
|E.2.2||Secondary objectives of the trial || |
|The key secondary objective is to assess the non-inferiority, or superiority of vaccination with ABNCoV2 compared to Comirnaty in terms of neutralizing antibodies against VOCs circulating at the time of the trial, again in Part A Cohort 1 and Cohort 2. Variants of concern might include Omicron (B.1.1.529), Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and/or Delta (B.1.617.2). If the non-inferiority margin is met for a VOC, superiority comparison will be carried out in the same cohort with the same type I error level. |
Another secondary objective is to assess the neutralizing antibody titers against the SARS-CoV-2 index virus in the immunogenicity subsets of the single-arm component (Part B), for Cohort 1 and Cohort 2.
|E.2.3||Trial contains a sub-study || No |
|E.3||Principal inclusion criteria || |
|1. Age ≥18 years at screening. |
2. Documented, previous completion of a primary vaccination regimen with locally authorized SARS CoV 2 vaccine(s) or completion of primary plus 1 boost vaccination (see definition of completed primary vaccination regimen and completed primary plus boost vaccination in Section 1.2), with last vaccination at least 3 months before screening. “Locally authorized” SARS CoV 2 vaccines are those that have received market approval or emergency use authorization in the country of enrollment.
3. Absence of acute medical illness, significant physical exam findings, or laboratory abnormalities, as determined by the investigator.
4. Informed consent, provided by the subject prior to performance of any trial-specific procedures; the subject has read, signed, and dated an informed consent form (ICF), having been advised of the risks and benefits of the trial in a language understood by the subject.
5. Body mass index (BMI) ≥18.5 and <40.
6. For female subjects of childbearing potential (WOCBP) and male subjects who are sexually active with a WOCBP, agreement to use an effective method of birth control from at least 30 days prior to administration of the vaccine until 30 days after the vaccination. A woman is considered of childbearing potential unless post-menopausal (defined as ≥12 months without a menstrual period at screening) or surgically sterilized (bilateral oophorectomy, bilateral tubal ligation, hysterectomy). Acceptable contraception methods are restricted to abstinence (only acceptable if refraining from heterosexual intercourse during the period of 30 days prior to administration of the vaccine until 30 days after the vaccination), double barrier contraceptives, vasectomy, intrauterine contraceptive devices, or licensed hormonal products.
7. For WOCBP, a negative serum pregnancy test at screening.
8. Negative tests for human immunodeficiency virus antibody (anti-HIV), hepatitis B surface antigen (HBsAG), and antibody to hepatitis C virus (HCV).
|E.4||Principal exclusion criteria|| |
|1. History of COVID-19 infection within the last 3 months before screening. |
2. Previous vaccination with a SARS-CoV-2 vaccine other than those mentioned in inclusion criterion #2.
3. Positive test for SARS-CoV-2 infection at screening.
4. Breastfeeding with intent to continue.
5. Acute or chronic medical condition that, in the opinion of the investigator, would render the trial procedures unsafe or would interfere with the evaluation of the responses.
6. History of myocarditis or pericarditis.
7. History of or active autoimmune disease. History of Guillain-Barré syndrome or Reye’s syndrome. Persons with vitiligo or thyroid disease taking thyroid replacement are not excluded.
8. Known or suspected impairment of immunologic functions including, but not limited to, known immunodeficiency syndrome.
9. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision at least 6 months prior to screening that is considered to have achieved cure. Subjects with history of skin cancer must not be vaccinated at the previous tumor site.
10. Laboratory parameters (such as complete blood count, serum biochemistry including aspartate aminotransferase [AST], alanine amino transferase [ALT], alkaline phosphokinase [ALP], bilirubin, or creatinine values), pulse rate, or blood pressure, or electrocardiogram (ECG) outside normal range at screening and deemed clinically relevant by the investigator.
11. Clinically significant mental disorder not adequately controlled by medical treatment.
12. Active or recent history (within 6 months before screening) of chronic alcohol abuse, or illicit drug abuse.
13. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
14. History of anaphylaxis or severe allergic reaction to any vaccine.
15. History of any vaccinations or plan to receive any vaccinations with a live vaccine within 30 days prior to or after trial vaccination.
16. History of any vaccinations or plan to receive any vaccinations with a non-live vaccine within 14 days prior to or after trial vaccination.
17. Recent blood donation (including platelets, plasma and red blood cells) within 4 weeks prior to screening, or planned blood donations during the active phase of the trial.
18. Chronic systemic administration (defined as more than 14 days) of >5 mg prednisone (or equivalent)/day, or any other immune-modifying drugs during a period starting 3 months prior to administration of the vaccine and ending 4 weeks after vaccination. The use of topical, inhaled, ophthalmic and nasal glucocorticoids is allowed.
19. History of organ transplantation, whether or not accompanied by chronic immunosuppressive therapy.
20. Administration or planned administration of immunoglobulins and/or any blood products during a period starting 3 months prior to administration of the vaccine and ending 4 weeks after vaccination. Receipt of packed red blood cells given for an emergency indication in an otherwise healthy person, and not required as ongoing treatment is not exclusionary (for example packed red blood cells given in emergency during an elective surgery).
21. Use of any investigational or non-registered drug or vaccine other than the trial vaccine within 30 days preceding the administration of trial vaccine, or planned administration of such a drug or vaccine throughout the trial.
22. Involvement in this trial as site personnel.
23. Known bleeding disorder that, in the opinion of the investigator, would contraindicate intramuscular injection.
|E.5 End points |
|E.5.1||Primary end point(s)|| |
|Part A: Geometric mean titer (GMT) of neutralizing antibodies against the SARS-CoV-2 index virus at 2 weeks after trial vaccination, in each Part A cohort. |
|E.5.1.1||Timepoint(s) of evaluation of this end point|| |
|Ratio of GMTs at 2 weeks after trial vaccination, for ABNCoV2 vaccine compared to Comirnaty vaccine, is within the non-inferiority margin of 0.67; specifically, the success criterion will be met within each cohort if the lower bound of the 2-sided 97.5% CI of the GMT ratio is ≥0.67. |
|E.5.2||Secondary end point(s)|| |
|If both Cohort 1 and Cohort 2 are tested for and meet the success criterion for the primary endpoint, VOCs will be tested in the cohort with the higher number of evaluable subjects, followed by the cohort with the smaller number of evaluable subjects if the success criterion is met in at least one of the tested VOCs in the cohort tested first. In the event only one cohort meets the success criterion for the primary endpoint, VOCs will be formally tested for the successful cohort only. |
|E.5.2.1||Timepoint(s) of evaluation of this end point|| |
|Ratios of GMTs for the VOCs at 2 weeks after trial vaccination, for ABNCoV2 vaccine compared to Comirnaty vaccine, will be tested using the non-inferiority margin of 0.67 as was used for the primary endpoint. The result will be based on the lower limit of a two-sided CI with coverage determined based on the number of VOCs circulating at the time of the trial. A Bonferroni correction will be employed for the simultaneous non-inferiority tests to control the trial-wide type I error. |
|E.6 and E.7 Scope of the trial |
|E.6||Scope of the trial |
|E.6.1||Diagnosis|| No |
|E.6.2||Prophylaxis|| No |
|E.6.3||Therapy|| No |
|E.6.4||Safety|| Yes |
|E.6.5||Efficacy|| Yes |
|E.6.6||Pharmacokinetic|| No |
|E.6.7||Pharmacodynamic|| No |
|E.6.8||Bioequivalence|| No |
|E.6.9||Dose response|| No |
|E.6.10||Pharmacogenetic|| No |
|E.6.11||Pharmacogenomic|| No |
|E.6.12||Pharmacoeconomic|| No |
|E.6.13||Others|| Yes |
|E.6.13.1||Other scope of the trial description|| |
|Tolerability, Immunogenicity, efficacy is inferred from immunogenicity |
|E.7||Trial type and phase |
|E.7.1||Human pharmacology (Phase I)|| No |
|E.7.1.1||First administration to humans|| No |
|E.7.1.2||Bioequivalence study|| No |
|E.7.1.3||Other|| No |
|E.22.214.171.124||Other trial type description|| |
|E.7.2||Therapeutic exploratory (Phase II)|| No |
|E.7.3||Therapeutic confirmatory (Phase III)|| Yes |
|E.7.4||Therapeutic use (Phase IV)|| No |
|E.8 Design of the trial |
|E.8.1||Controlled|| Yes |
|E.8.1.1||Randomised|| Yes |
|E.8.1.2||Open|| Yes |
|E.8.1.3||Single blind|| No |
|E.8.1.4||Double blind || No |
|E.8.1.5||Parallel group|| No |
|E.8.1.6||Cross over || No |
|E.8.1.7||Other|| Yes |
|E.126.96.36.199||Other trial design description|| |
|Phase 3 Trial in Two Parts—Randomized, Double-blind, Active Controlled and Open-label, Single-arm |
|E.8.2|| Comparator of controlled trial |
|E.8.2.1||Other medicinal product(s)|| Yes |
|E.8.2.2||Placebo || No |
|E.8.2.3||Other|| No |
|E.8.2.4||Number of treatment arms in the trial||2 |
|E.8.3|| The trial involves single site in the Member State concerned || No |
|E.8.4|| The trial involves multiple sites in the Member State concerned || Yes |
|E.8.4.1||Number of sites anticipated in Member State concerned||8 |
|E.8.5||The trial involves multiple Member States|| Yes |
|E.8.5.1||Number of sites anticipated in the EEA||13 |
|E.8.6 Trial involving sites outside the EEA |
|E.8.6.1||Trial being conducted both within and outside the EEA|| Yes |
|E.8.6.2||Trial being conducted completely outside of the EEA|| No |
|E.8.6.3||If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned|| |
|United States |
|E.8.7||Trial has a data monitoring committee|| Yes |
|E.8.8|| Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial || |
|E.8.9 Initial estimate of the duration of the trial |
|E.8.9.1||In the Member State concerned years|| |
|E.8.9.1||In the Member State concerned months||12 |
|E.8.9.1||In the Member State concerned days|| |
|E.8.9.2||In all countries concerned by the trial months||14 |