Clinical Trials Register

Summary
EudraCT Number:	2021-002171-19
Sponsor's Protocol Code Number:	HEVACC
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-04-27
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2021-002171-19

A.3

Full title of the trial

Heterologous vaccination with a Vaxzervia (ChAdOx1-S) prime and a Comirnaty (BNT162b2) boost

Heterologe Impfung mit Vaxzervia (ChAdOxl-S, AstraZeneca) gefolgt von Comirnaty (BNT162b2, Pfizer)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Heterologous vaccination with a Vaxzervia (ChAdOx1-S) prime and a Comirnaty (BNT162b2) boost

Heterologe Impfung mit Vaxzervia (ChAdOxl-S, AstraZeneca) gefolgt von Comirnaty (BNT162b2, Pfizer)

A.4.1

Sponsor's protocol code number

HEVACC

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Medizinische Universität Innsbruck, Institut für Virologie
B.1.3.4	Country	Austria
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Medizinische Universität Innsbruck
B.4.2	Country	Austria
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medizinische Universität Innsbruck
B.5.2	Functional name of contact point	Sponsor representative and PI
B.5.3	Address:
B.5.3.1	Street Address	Peter-Mayr-Straße 4b
B.5.3.2	Town/ city	Innsbruck
B.5.3.3	Post code	6020
B.5.3.4	Country	Austria
B.5.4	Telephone number	00435212900371737
B.5.6	E-mail	dorothee.vonlaer@i-med.ac.at

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Comirnaty concentrate for dispersion for injection COVID-19 mRNA Vaccine (nucleoside modified)
D.2.1.1.2	Name of the Marketing Authorisation holder	BioNTech Manufacturing GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Comirnaty
D.3.4	Pharmaceutical form	Dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COVID-19 mRNA vaccine
D.3.9.3	Other descriptive name	COVID-19 mRNA vaccine (nucleoside-modified)
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vaxzevria suspension for injection COVID-19 Vaccine (ChAdOx1-S [recombinant])
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vaxzevria
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COVID-19 Vaccine (ChAdOx1-S [recombinant])
D.3.9.3	Other descriptive name	COVID-19 vaccine AstraZeneca (ChAdOx1 nCoV-19)
D.3.9.4	EV Substance Code	SUB207764
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2.5 × 10^8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vaxzevria suspension for injection COVID-19 Vaccine (ChAdOx1-S [recombinant])
D.2.1.1.2	Name of the Marketing Authorisation holder	AstraZeneca AB
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vaxzevria
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	COVID-19 Vaccine (ChAdOx1-S [recombinant])
D.3.9.3	Other descriptive name	COVID-19 vaccine AstraZeneca (ChAdOx1 nCoV-19)
D.3.9.4	EV Substance Code	SUB207764
D.3.10	Strength
D.3.10.1	Concentration unit	U unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2.5 × 10^8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another 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.1.1

Medical condition(s) being investigated

Immunization for SARS-CoV-2

E.1.1.1

Medical condition in easily understood language

Immunisierung gegen SARS-CoV-2

E.1.1.2

Therapeutic area

Not possible to specify

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10021433
E.1.2	Term	Immunization
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary objectives:
1. To determine whether the immune response to vaccine SARS‐CoV‐2 spike protein is at least as effective for the heterologous prime‐boost regime Vaxzevria followed by Comirnaty as in the
approved homologous Vaxzevria and Comirnaty regimen.
2. To determine immune responses in non‐responders after a third immunization
3. To determine immune responses all participants after a third immunization

E.2.2

Secondary objectives of the trial

1. Potentially show clinical efficacy against infection, especially with B.1.351, B.1.1.7+E484K and other immune escape variants
2. To analyze in detail safety and tolerability after the second vaccination especially in the heterologous arm. (clinical, lab)
3. To evaluate the clinical course and outcome of COVID‐19 diseases after vaccination with ChAdOx1‐S prime & boost vs. ChAdOx1‐S prime and BNT162b2 boost vs BNT162b2 prime & boost
4. To analyze safety and tolerability after the 3rd dose vaccination (clinical, lab)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subject provides written informed consent
2. Participant is ≥ 18 and ≤ 65 years of age on the day of signing the ICF
3. Individuals that are eligible for vaccination according to the Austrian vaccination plan.
4. Participants that have been vaccinated with either ChAdOx1-S prime within the last 12 weeks or BNT162b2 prime within the last 3 – 6 weeks
5. Subject understands and agrees to comply with study procedures
6. Subject must be willing to be contacted by telephone or willing to complete an eDiary during study participation
7. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:
- has a negative urine pregnancy test at screening
- has agreed to practice adequate contraception from providing consent until 3 months after administration of study vaccine
- is not currently breastfeeding

Adequate female contraception is defined as consistent and correct use of an approved contraceptive method, for example:
• Barrier method (condoms, diaphragm, cervical cap) used in conjunction with spermicide
• Prescription hormonal contraceptive taken administered via oral (pill), transdermal (patch), subdermal or IM route
• Intrauterine device
• Sterilization of a female participant`s monogamous male partner prior to study inclusion
Cave: periodical abstinence (eg calendar, ovulation, symptothermal,...) and withdrawal are not acceptable methods of contraception.

8. Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as: surgically sterile (history of bilateral dubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (amenorrhea for  12 consecutive months prior to Screening without an alternative medical cause).
9. Participants agrees to not donate bone marrow, blood and blood products from the study vaccine administration until 3 months after receiving the study vaccine

Amendment protocol 2021-08-18: 3rd vaccination

1. Subjects that have received the second dose of vaccination within this study.

2. No neutralizing antibodies on day 90 post second dose (only for participants that will receive the third dose between day 110 and 180). All other participants will be offered a third dose between
day 200 and 260 after the second dose, independent of their antibody titers.
3. Subject provides written informed consent
4. Subject understands and agrees to comply with study procedures
5. Subject must be willing to be contacted by telephone or willing to complete an eDiary during study participation
6. Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:
- has a negative urine pregnancy test at screening
- has agreed to practise adequate contraception from providing consent until 3 months after administration of study vaccine
- is not currently breastfeeding

8. Participants agrees to not donate bone marrow, blood and blood products from the study vaccine administration until 3 months after receiving the study vaccine

E.4

Principal exclusion criteria

1. Participant has already received full vaccination against SARS-CoV-2
2. Prior administration of an investigational coronavirus (SARS-CoV, MERS-CoV) vaccine or current/planned simultaneous participation in another interventional study to either prevent or treat COVID-19
3. Participant has received/plans to receive a non-study vaccine within 14 days prior to or after any dose of IP
4. Participant has a contraindication to IM injections and blood draws (eg, bleeding disorders)
5. Participants has a known or suspected allergy or history of anaphylaxis, urticaria or other significant adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine; refer to the IB)
6. Subjects with previous positive PCR-test result for SARS-CoV-2 or positive anti-SARS-CoV-2 N protein antibody test
7. History of leukemia, lymphoma, or underlying bone marrow disorder (eg, myelodysplasia, myeloma, myeloproliferative disorder) or history of bone marrow transplant.
8. Malignancy that required treatment with chemotherapy, immunotherapy, radiation therapy, or other antineoplastic target therapies within 24 months prior to study enrollment.
9. Has participated in an interventional clinical study within 30 days prior to study inclusion

Amendment protocol 2021-08-18: 3rd vaccination

1. Participant already received a third dose of vaccination.
2. Subjects with positive PCR‐test result for SARS‐CoV‐2 after study enrolment or a positive anti‐SARS‐CoV‐2 N antibody test on day 180.

E.5 End points

E.5.1

Primary end point(s)

1a Level of neutralizing antibodies against wild‐type and immune escape variants in the 3 study groups at 10, 30, 90 and 180 days post boost.
1b Level of neutralizing antibodies against wild‐type and immune escape variants at 10, 30, 90 and 180 days post 3rd immunization.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 10, Day 30, Day 90, Day 180

Amendment protocol 2021-08-18: 3rd vaccination
Day 10, Day 30, Day 90, Day 180 after 3rd vaccination

E.5.2

Secondary end point(s)

1. Level of T cell responses against SARS‐CoV‐2 spike protein peptides pools per subgroup at 30 days.
2. Occurrence of breakthrough infection with wild type, B.1.351 and other immune escape variants of SARS‐CoV‐2
3. Occurrence of adverse events, serious adverse events and adverse events of special interest
4. The clinical course (hospitalization, ICU admission) and outcome of COVID‐19 diseases (recovery, long‐Covid mortality).
5. Occurrence of adverse events, serious adverse events and adverse events of special interest after 3rd immunization
6. Level of T cell responses against SARS‐CoV‐2 spike protein peptides pools in non‐responders after 3rd immunization
7. Occurrence of breakthrough infection with wild type, B.1.351 and other immune escape variants of SARS‐CoV‐2 after 3rd immunization

E.5.2.1

Timepoint(s) of evaluation of this end point

Day 1 - day 10 and weekly antigen-tests until day 180 after Boost shot

Amendment protocol 2021-08-18: 3rd vaccination
Day 1 - day 10 and weekly antigen-tests until day 180 after 3rd vaccination

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Amendment protocol 2021-08-18: arm Vaxzevria twice had to be closed, design switched to open

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

LVLS

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

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

2800

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

3000

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-05-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-07-11

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials