Clinical Trials Register

Summary
EudraCT Number:	2021-001040-10
Sponsor's Protocol Code Number:	CoVVac
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:	2021-03-26
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

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A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2021-001040-10

A.3

Full title of the trial

Humoral and cellular immune response to COVID-19 vaccines in immunocompromised and healthy individuals – The CoVVac study

A.3.1

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

Humoral (antibodies) and cellular (white blood cells) immune response to COVID-19 vaccines in immunocompromised (people with impaired immune system) and healthy individuals – The CoVVac study

A.3.2

Name or abbreviated title of the trial where available

The CoVVac study

A.4.1

Sponsor's protocol code number

CoVVac

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	Medical University of Graz
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	Medical University of Graz
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	Medical University of Graz
B.5.2	Functional name of contact point	Clinical Trials Information
B.5.3	Address:
B.5.3.1	Street Address	Auenbruggerplatz 2
B.5.3.2	Town/ city	Graz
B.5.3.3	Post code	8036
B.5.3.4	Country	Austria
B.5.6	E-mail	martin.stradner@medunigraz.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
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.3.4	Pharmaceutical form	Concentrate for solution 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)	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	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	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	Spikevax dispersion for injection COVID-19 mRNA Vaccine (nucleoside modified)
D.2.1.1.2	Name of the Marketing Authorisation holder	MODERNA BIOTECH SPAIN, S.L.
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.3.4	Pharmaceutical form	Concentrate for solution 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 Moderna (CX-024414)
D.3.9.4	EV Substance Code	SUB207171
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	100
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	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: 3
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	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.3.4	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
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	2.5E8
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	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.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

Active immunisation to prevent COVID-19 in immunocompromised individuals.

E.1.1.1

Medical condition in easily understood language

Active immunisation to prevent coronavirus disease 2019 in individuals with weak immune system.

E.1.1.2

Therapeutic area

Health Care [N] - Population Characteristics [N01]

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

E.2 Objective of the trial

E.2.1

Main objective of the trial

Characterization of the anti-SARS-CoV-2 humoral immune response after vaccination with a focus on the anti-spike protein response: an analysis in immunocompromised patients compared to healthy controls.

E.2.2

Secondary objectives of the trial

Compare T cell response of healthy & immunodeficient subject
Differnce in seroconversion or T cell response between different vaccines
Impact of immune system´s aging to humoral & cellular immune response
Impact of the various forms of immunosuppression on the vaccine-induced response
Impact of previous SARS-CoV-2 infection and
Role of previous asymptomatic SARS-CoV-2 infection on the vaccine induced response
Compare immune response of the various vaccines & participants
Difference in the induction of secretory IgA and serum IgA in comparison to the serum IgG and IgM response
Influence of previous infections caused by endemic CoV on the vaccine response
Difference in the induction of neutralizing antibodies in subsets of immunocompromised & in COVID-19 recovered individuals compared to COVID-19 naïve controls
Difference in the neutralizing capacity of antibodies after vaccination towards the emerging SARS-CoV-2 variants
Humoral & cellular effect of a booster vaccination

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

In order to be enrolled, participants must be 18 years or older, able to understand study procedures, provide written informed consent (Biobank informed consent and study specific informed consent), and meet one of the following inclusion criteria:
1. Noninfectious immunocompetent participants (i.e., healthy participants) as determined by medical history and clinical judgement.
or
2. Patients with primary immunodeficiencies
or
3. Patients with B-cell depleting therapy due autoimmune disease
or
4. Patients with benign and malignant hematological diseases receiving specific treatments with known immunosuppressive effects including cytotoxic agents, systemic corticosteroids, monoclonal antibodies and targeted therapies.
or
5. Patients with active hematological diseases and secondary immunoglobulin deficiency (e.g. CLL, MM) currently not receiving specific treatment.
or
6. Patients >3 months but <12 months after autologous HSCT.
or
7. Patients >3 months but <12 months after allogeneic HSCT.
or
8. Recipients of HSCT >12 months after allogeneic HSCT but under immunosuppressive therapy.
or
9. Patients with chronic GvHD and persistent immunodeficiency.

E.4

Principal exclusion criteria

Subjects meeting any of the following criteria cannot be enrolled into the trial:

Healthy participants
1. Presence of diseases or therapies that are likely to interfere with the immune response to vaccination.
2. Presence of a disease requiring change in therapy during 4 weeks before enrollment.
3. Any contraindications to the vaccine planned to receive as listed in the product characteristics.
4. Lack of willingness to undergo serial blood draws and attend follow-up appointments.
5. Women who are pregnant or breastfeeding.
6. Previous vaccination with any coronavirus vaccine.
7. Persons who are not willing to sign the informed consents (biobank informed consent and study specific informed consent).

Immunodeficient participants
1. Patients with hematological diseases within three months from B-cell-depleting immunotherapy (rituximab, ofatumumab, obinutuzumab, blinatumomab, CAR-T cells).
2. Patients with hematological malignancies in remission and >12 months after end of specific therapy.
3. Patients within three months from HSCT.
4. Any contraindications to the vaccine planned to receive as listed in the product characteristics.
5. Lack of willingness to undergo serial blood draws and attend follow-up appointments.
6. Women who are pregnant or breastfeeding.
7. Previous vaccination with any coronavirus vaccine (exception: if serum prior to vaccination is available from the biobank).
8. Patients who are not willing to sign the informed consents (biobank informed consent and study specific informed consent).

E.5 End points

E.5.1

Primary end point(s)

The seroconversion leading to anti-SARS-CoV-2 spike protein humoral immune response at day 21-28 after the second vaccination measured by SARS-CoV-2 antigen-binding Ig assay, comparing immunocompromised patients to healthy controls.

E.5.1.1

Timepoint(s) of evaluation of this end point

Day 21-28 after the second vaccination.

E.5.2

Secondary end point(s)

• Seroconversion measured by SARS-CoV-2 antigen-binding Ig assay 6 and 12 months after second, 3-5 weeks and 6 months after third vaccination
• Concentrations of recombinant S protein-binding IgG depending on prior exposure to SARS-CoV-2.
• Concentrations of secretory and serum IgA in comparison to IgG and IgM after second and third vaccination in immunocompromised, in recovered individuals and in healthy controls.
• Cytokine production of T cells after SARS-CoV-2 antigen exposure, measured by FACS and ELISpot
• Identification of parameters predicting the response to COVID-19 vaccinations: prior CoV infection (cross-reactive antibodies), quantitative immunoglobulins, B cell subsets, T cell subsets; T cell aging (TCR diversity, telomere length, TREC levels)
• Neutralizing capacity of antibodies in respect of different SARS-CoV-2 variants
• Correlation of dietary inflammation index and subcutaneous fat thickness sum with seroconversion after second vaccination.

E.5.2.1

Timepoint(s) of evaluation of this end point

After second and third vaccination and 6 and months after vaccination, respectively.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

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)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

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

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:

195

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

195

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

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2021-03-26.

Yes

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

390

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

2021-04-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-20

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