Clinical Trial Page

Summary
EudraCT Number:2021-005504-36
Sponsor's Protocol Code Number:ABNCoV2-03
National Competent Authority:Belgium - FPS Health-DGM
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2022-08-18
Trial results
A. Protocol Information
A.1Member State ConcernedBelgium - FPS Health-DGM
A.2EudraCT number2021-005504-36
A.3Full title of the trial
Covid-19: Evaluation of the Immunogenicity, Safety, and Tolerability of a Single Dose of ABNCoV2 Vaccine in Adult Subjects Previously Vaccinated for SARS-CoV-2: a Phase 3 Trial in Two Parts—Randomized, Double-blind, Active Controlled and Open-label, Single-arm
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A study to Evaluate Immunogenicity, Safety and Tolerability of a Single Dose of ABNCoV2 Vaccine in Adult Subjects Previously Vaccinated for SARS-CoV-2
A.4.1Sponsor's protocol code numberABNCoV2-03
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorBavarian Nordic A/S
B.1.3.4CountryDenmark
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportBavarian Nordic A/S
B.4.2CountryDenmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationBavarian Nordic GmbH
B.5.2Functional name of contact pointclinical-mailbox
B.5.3 Address:
B.5.3.1Street AddressFraunhoferstrasse 13
B.5.3.2Town/ cityPlanegg (Martinsried)
B.5.3.3Post code82152
B.5.3.4CountryGermany
B.5.6E-mail[email protected]
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.2Product code ABNCoV2
D.3.4Pharmaceutical form Dispersion for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNCOVID-19 Vaccine (recombinant, non-adjuvanted)
D.3.9.3Other descriptive nameABNCoV2
D.3.9.4EV Substance CodeSUB221263
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number100
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Comirnaty 30 micrograms/dose concentrate for dispersion for injection COVID-19 mRNA Vaccine (nucleoside modified)
D.2.1.1.2Name of the Marketing Authorisation holderBioNTech Manufacturing GmbH
D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameComirnaty 30 micrograms/dose concentrate for dispersion for injection COVID-19 mRNA Vaccine
D.3.4Pharmaceutical form Concentrate for dispersion for injection
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPIntramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNTozinameran
D.3.9.3Other descriptive nameComirnaty
D.3.9.4EV Substance CodeSUB210693
D.3.10 Strength
D.3.10.1Concentration unit µg microgram(s)
D.3.10.2Concentration typeequal
D.3.10.3Concentration number30
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product No
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
COVID-19 disease
E.1.1.1Medical condition in easily understood language
COVID-19 disease
E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 23.1
E.1.2Level PT
E.1.2Classification code 10084457
E.1.2Term COVID-19 immunisation
E.1.2System Organ Class 10042613 - Surgical and medical procedures
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main 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.2.2Secondary 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.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
1. Age ≥18 years at screening.
2. Documented, previous administration of locally authorized SARS-CoV-2 vaccine(s) for primary vaccination only or for primary plus 1 boost vaccination, 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.4Principal 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 an inactivated 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.
E.5 End points
E.5.1Primary 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.5.1.1Timepoint(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.5.2Secondary 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.5.2.1Timepoint(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.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy No
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Tolerability, Immunogenicity, efficacy is inferred from immunogenicity
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other Yes
E.8.1.7.1Other 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.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
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.8.4.1Number of sites anticipated in Member State concerned5
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA15
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Belgium
Denmark
United States
E.8.7Trial 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
LVLS
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years
E.8.9.1In the Member State concerned months6
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial months7
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 3000
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 1000
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers Yes
F.3.2Patients No
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others Information not present in EudraCT
F.4 Planned number of subjects to be included
F.4.1In the member state500
F.4.2 For a multinational trial
F.4.2.1In the EEA 1000
F.4.2.2In the whole clinical trial 4000
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
None
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2022-09-30
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2022-10-05
P. End of Trial
P.End of Trial StatusOngoing