Immunogenicity:To determine the immune response in terms of GMT fold-rise for neutralising antibodies against SARS-CoV-2 following a single booster dose with VLA2001Safety:To assess tolerability of a VLA2001 booster vaccination
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
COVID-19
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Immunogenicity:
- GMT fold-rise for neutralising antibodies against SARS-CoV-2 at Day 15
following a single booster dose with VLA2001
Safety:
- Frequency and severity of solicited AEs (local and systemic reactions) within
7 days after the VLA2001 booster vaccination
Secondary outcome
Immunogenicity:
- Immune response as determined by the GMT of SARS-CoV-2-specific neutralizing
antibodies at Visit 1 (pre-booster, Day 1) and Visit 2 (Day 15).
- Proportion of participants achieving an at least 2-, 4-, 10- or 20-fold rise
over baseline (pre-booster) in terms of neutralizing antibodies to SARS-CoV-2
S-protein at Visit 2 (Day 15).
- GMT fold-rise of IgG antibodies to the SARS-CoV-2 S-protein at Day 15.
- Immune response as determined by the GMT of IgG antibodies to the SARS-CoV-2
S-protein at Visit 1 (pre-booster, Day 1) and Visit 2 (Day 15).
- Proportion of participants achieving an at least 2-, 4-, 10- or 20-fold rise
over baseline (pre-booster) in terms of IgG antibodies to SARS-CoV-2 S-protein
at Visit 2 (Day 15).
- Assessment of T-cell responses from PBMCs after in vitro stimulation with
SARS-CoV-2 antigens using e.g., ELISpot (IFN) or intracellular cytokine
staining (IL-2, IL-4, IL-5, IL-13, TNF, IFN) at Day 1 and Day 15.
Safety:
- Frequency and severity of any AE up to 4 weeks after vaccination
- Frequency and severity of unsolicited AEs up to 4 weeks after vaccination
- Frequency and severity of any unsolicited vaccine-related AE up to 4 weeks
after vaccination
- Frequency and severity of any serious adverse event (SAE) up to 4 weeks after
vaccination and up to Day 180.
- Frequency and severity of any adverse event of special interest (AESI) up to
4 weeks after vaccination and up to Day 180.
Background summary
Since December 2019, coronavirus-induced disease 2019 (COVID-19) has spread
around the world, with over 262 million confirmed cases as of the December 1,
2021 by the WHO. It is not known if SARS-CoV-2 will remain as worldwide
pandemic. It is also not known how long the immunity that is acquired after
symptomatic or asymptomatic SARS-CoV-2 infection can last.
COVID-19 vaccination programs worldwide have been focusing on achieving
high-levels of population immunity through the primary COVID-19 vaccine series.
Waning antibody levels are biologically inevitable following vaccination, and
as the numbers of breakthrough cases increase there is a need for a long term
COVID-19 immunization strategy.
This trial aims to generate safety and immunogenicity data following booster
vaccination with VLA2001 for participants who have received homologous primary
immunization with either BNT162b2 (Comirnaty) or Spikevax (previously COVID-19
Vaccine Moderna) in the national deployment vaccination campaign as well as
generating data on the impact and influence exposure to natural infection has
on the immune response prior and post a booster dose with VLA2001 with regards
to the cross-reactivity against other variants of concern.
Furthermore, this trial aims to generate safety and immunogenicity data
following booster vaccination with VLA2001 for participants who had been
previously infected with SARS-CoV-2.
The phase 2 part of the study involves administration of a double dose (1.0 mL
instead of 0.5 mL) to investigate the safety and immunogenicity of a single
double dose in participants above 50 years of age. The rationale for
investigating a double dose is to evaluate whether a double dose will result in
higher immunogenicity and to confirm a favourable safety. The standard dose of
0.5 mL was shown to have a very favourable safety and tolerability profile in
phase 3 clinical studies and the planned increase of volume to 1.0 mL has been
evaluated in pre-clinical toxicology studies.
Study objective
Immunogenicity:
To determine the immune response in terms of GMT fold-rise for neutralising
antibodies against SARS-CoV-2 following a single booster dose with VLA2001
Safety:
To assess tolerability of a VLA2001 booster vaccination
Study design
This is a multicentric, open label, phase 2/3 clinical study to investigate the
safety, tolerability, and immunogenicity of a VLA2001 booster vaccination
(standard dose in adults aged >=18 to <=50 years or double dose in volunteers
aged *50 years). Volunteers who are either generally healthy or are with a
stable medical condition will be enrolled. In total, approximately 275
participants were planned to be enrolled.
It was planned to enroll approximately 25% of participants who are above 65
years into the cohorts with participants above 50 years of age.
The VLA2001 booster (standard dose of 0.5 mL or double dose of 1.0 mL) will be
applied:
Cohort 1 and Cohort 2: groups A and B:
at least 6 months after vaccination with mRNA COVID-19 vaccine
Cohort 1 and Cohort 2: groups C and D:
at least 6 months after vaccination with mRNA COVID-19 vaccine
or
at least 4 months after a documented PCR or antigen test for confirmed
SARS-CoV-2 infection in case the infection occurred after the administration of
the last dose of mRNA COVID-19 vaccine
Cohort 3: In addition, the VLA2001 booster (standard dose of 0.5 mL for
participants >=18 to <=50 years or double dose of 1.0 mL for *50 years) will be
applied at least 4 months after documented PCR or antigen test confirmation of
natural SARS-CoV-2 infection.
All visits will be conducted at the clinical site on an outpatient basis or as
home visits. Immunogenicity and safety will be assessed up to Month 12 after
the booster vaccination. All participants will be observed for immediate AEs
and/or reactogenicity for at least 30 minutes after the administration of the
vaccine. Participants will be provided with an electronic Diary (e-Diary) and
will be trained to record specifically solicited, predefined systemic and local
symptoms daily for 7 days following the booster vaccination as well as any
additional AEs during the follow-up period up to Day 15.
All unsolicited AEs need to be documented in the source documents throughout
the study and will be captured in the respective AE section of the eCRF up to
Visit 3. Serious adverse events as well as AESIs will continue to be documented
in the eCRF until the end of the study.
Intervention
A single COVID-19 booster vaccination
Study burden and risks
Risks associated with vaccination with an inactivated virus vaccine are
considered low. The following risks are expected:
Injection site reactions: pain, tenderness, itching, swelling, redness,
induration
Systemic reactions: fatigue, headache, fever, nausea, vomiting
Blood draws: pain, hematoma and in very rare cases an infection at the
venepuncture site
Benefits:
A vaccine for SARS-CoV-2 will help reduce the severe and unprecedented
disruption the pandemic has caused to people*s lives worldwide. It will reduce
the burden of healthcare services that had to find extra resources to care for
critically ill people with COVID-19 and will also reduce the risk to frontline
workers of contracting the virus.
Campus Vienna Biocenter 3
Vienna 1030
AT
Campus Vienna Biocenter 3
Vienna 1030
AT
Listed location countries
Age
Inclusion criteria
Participants must meet all inclusion criteria to be eligible for the study.
ALL PARTICIPANTS:
1. Participants of either gender aged 18 years and older at screening
2. Participants must have read, understood, and signed the informed consent
form (ICF)
3. Medically stable such that, according to the judgment of the investigator,
hospitalization within the study period is not anticipated and the participant
appears likely to be able to remain on study through the end of
protocol-specified follow-up.
4. Participant has a Body Mass Index (BMI) of 18.0-30.0 kg/m2, inclusive, at
screening (Visit 0).
5. Must be able to attend all visits of the study and comply with all study
procedures, including daily completion of the e-diary for 7 days following each
vaccination.
6. Women of childbearing potential (WOCBP), who are sexually active with a man,
must be able and willing to use at least 1 highly effective method of
contraception (i.e. implant contraceptive, intra-uterine device (IUD)
containing either copper or levonorgestrel, male sterilization [vasectomy],
female sterilization, injectable contraceptive, oral contraceptive pill,
vaginal contraceptive ring, barrier type of birth control measure) from study
start until a minimum of 3 months after receiving the booster vaccine.
7. WOCBPs must have a negative pregnancy test prior to the booster vaccination.
Cohort Specifics:
Cohort 1A (>/= 18 years): 2 doses of mRNA, no infection
Cohort 1B (18-50 years): 3 doses of mRNA, no infection
Cohort 1C (18-50 years): 2 doses of mRNA, PCR or antigen confirmed SARS-CoV-2
infection
Cohort 1D (18-50 years): 3 doses of mRNA, PCR or antigen confirmed SARS-CoV-2
infection
Cohort 2A (> 50 years): 2 doses of mRNA, no infection
Cohort 2B (> 50 years): 3 doses of mRNA, no infection
Cohort 2C (> 50 years): 2 doses of mRNA, PCR or antigen confirmed SARS-CoV-2
infection
Cohort 2D (> 50 years): 3 doses of mRNA, PCR or antigen confirmed SARS-CoV-2
infection
Cohort 3 (>/= 18 years): PCR or antigen confirmed SARS-CoV-2 infection, but not
vaccinated
Note: Rapid antigen test results can be considered as proof of previous
Covid-19 infection but only if the antigen test results have been officially
documented or registered in an official system - as for the PCR test results,
in all cases, a paper document must be available/printable to be considered
sufficient proof of a previous infection prior to enrollment (in the relevant
Cohorts).
Exclusion criteria
Participants will not be eligible for the study if they meet any of the
exclusion criteria.
1. Participant is pregnant or planning to become pregnant within 3 months after
booster administration
2. History of allergy to any component of the vaccine
3. Participant had close contact to persons with confirmed SARS-CoV-2 infection
within 30 days prior to screening (Visit 0)
4. Participant has participated in a clinical study involving an
investigational SARS-CoV-2 vaccine or has received or plans to receive a
licensed SARS-CoV-2 vaccine during the duration of the study
5. Significant infection or other acute illness, including fever > 37.8 °C
within 48 hours before vaccination
6. Positive SARS-CoV-2 rapid Antigen test result during screening (Visit 0) or
Visit 1
7. Participant has a known or suspected defect of the immune system, such as
participants with congenital or acquired immunodeficiency, including infection
with HIV, status post organ transplantation or immuno-suppressive therapy
within 4 weeks prior to the expected day of vaccination (Visit 1).
8. Participant has a history of malignancy in the past 5 years other than
squamous cell or basal cell skin cancer. If there has been surgical excision or
treatment more than 5 years ago that is considered to have achieved a cure, the
participant may be enrolled. A history of hematologic malignancy is a permanent
exclusion. Participants with a history of skin cancer must not be vaccinated at
the previous tumour site
9. History of drug dependency or current use of drug of abuse or alcohol abuse
at screening
10. Significant blood loss (> 450 mL) or has donated 1 or more units of blood
or plasma within 6 weeks prior to the expected day of first vaccination (Visit
1)
11. History of clinically significant bleeding disorder (e.g., factor
deficiency, coagulopathy, or platelet disorder), or prior history of
significant bleeding or bruising following IM injections or venepuncture
12. Severe and uncontrolled ongoing autoimmune or inflammatory disease, History
of Guillain-Barre syndrome or any other demyelinating condition
13. Any other significant disease, disorder or finding which in the opinion of
the investigator may significantly increase the risk to the volunteer because
of participation in the study, affect the ability of the volunteer to
participate in the study or impair interpretation of the study
Prior/concomitant therapy:
14. Receipt of immunoglobulin or another blood product within the 3 months
before expected day of vaccination (Visit 1) in this study or those who expect
to receive immunoglobulin or another blood product during this study
15. Receipt of medications to treat or prevent COVID-19 (except licensed mRNA
vaccine for participants of Cohort 1 and 2)
16. Receipt of any vaccine (licensed or investigational), other than licensed
influenza vaccine or for medical emergencies such as tetanus or rabies
exposure, within 28 days prior to the expected day of first vaccination (Visit
1)
Others:
17. Any member of the study team or sponsor
18. An immediate family member or household member of the study*s personnel
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-000035-23-NL |
| ClinicalTrials.gov | NCT05364242 |
| CCMO | NL80449.000.22 |