COV-COMPARE: Study To Compare The Immunogenicity Against COVID-19, Of VLA2001 Vaccine To AZD1222 Vaccine

Sponsor

Valneva Austria GmbH (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04864561

Collaborator

(none)

4,679

Enrollment

Locations

Arms

Anticipated Duration (Months)

150.9

Patients Per Site

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multicentre, randomized, observer-blind, active-controlled, superiority, study in adults to compare the immunogenicity of VLA2001 to AZD1222 in terms of GMT of SARS-CoV-2-specific neutralising antibodies. Furthermore, VLA2001 will be compared to placebo in an adolescent population.

Condition or Disease	Intervention/Treatment	Phase
SARS-CoV-2 Virus Infection	Biological: VLA2001 Biological: AZD1222 Biological: VLA2001 - adolescent part Biological: Placebo	Phase 3

Detailed Description

Approximately 4000 Adult participants will be recruited in the study. About 3000 participants aged 30 years and above will be randomized in a 2:1 ratio to receive 2 intramuscular recommended doses of either VLA2001 (n=2000) or AZD1222 (n=1000). In addition, approximately 1000 subjects aged 18-29 years will participate in this study in a non-randomized, open-label fashion to receive VLA2001. The 2 doses of vaccination for both vaccines will be administered 28 days apart, on Days 1 and 29. All visits will be conducted at the clinical site on an outpatient basis.

Approximately 660 Adolescent participants will be recruited and randomized in a 1:1 ratio to receive 2 intramuscular doses of either VLA2001 (n=330) or placebo (n=300). Adolescents randomized to receive VLA2001, will receive a booster vaccination with VLA2001 at Day 208. Participants in the placebo group will receive a 2-dose primary immunization with VLA2001 at day 208 and the second vaccination 28 days later. For safety reasons, the first 16 adolescents will be enrolled in an open label, non-randomized manner (sentinel dosing).

Immunogenicity (neutralizing antibody titers) and safety will be assessed up to months 12 after the first vaccination.

Participants will be provided with an electronic Diary (e-Diary) and will be trained to record specifically solicited systemic and local symptoms daily as well as any additional AEs during follow-up period after each of both vaccinations up to the next visit to the site until Day 43 visit has been completed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

4679 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Masking Description:

study participants aged 18-29 years at the time of enrolment are unblinded, study participant aged 12-18 and 30 years above at the time of enrolment are blinded (sentinel group is unblinded) until 28 days after vaccination on day 208, when all participants will be unblinded.

Primary Purpose:

Prevention

Official Title:

A Randomized, Observer-Blind, Controlled, Superiority Study To Compare The Immunogenicity Against COVID-19, Of VLA2001 Vaccine To AZD1222 Vaccine, In Adults Including a Randomized, Observer-blind, Placebo Controlled Part in Adolescents (≥12 to <18 Years)

Actual Study Start Date :

Apr 26, 2021

Anticipated Primary Completion Date :

Nov 10, 2022

Anticipated Study Completion Date :

Sep 24, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: VLA2001 <30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222	Biological: VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxide 2 vaccinations 28 days apart
Active Comparator: AZD1222 <30 years will receive VLA2001; participants aged ≥30 years will be randomised 2:1 to receive VLA2001 or AZD1222	Biological: AZD1222 2 vaccinations 28 days apart AZD1222 is a recombinant, replication-defective chimpanzee adenovirus expressing the SARS-CoV-2 S surface glycoprotein.
Active Comparator: VLA2001 - adolescent part ≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo	Biological: VLA2001 - adolescent part whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in combination with aluminium hydroxid 2 vaccinations 28 days apart and with a booster vaccination on day 208. Placebo group will receive VLA2001 on day 208 and following second vaccination 28 days later.
Placebo Comparator: Placebo ≥12 to < 18 years will be randomized 1:1 to receive VLA2001 or Placebo	Biological: Placebo 2 vaccinations 28 days apart with placebo (PBS buffer based on Dulbecco's PBS media formulation without Calcium and Magnesium )

Outcome Measures

Primary Outcome Measures

Immune response measured after completion of a 2-dose immunization schedule, as determined by the geometric mean titer (GMT) of SARS-CoV-2-specific neutralizing antibodies [Day 43]
Immune response measured after completion of a 2-dose immunization schedule, as determined by Seroconversion (definded as 4-fold increase from baseline) of SARS-CoV-2-specific neutralizing antibodies [Day 43]
Frequency and severity of any Adverse Events (AE) [Up to Day 43 post-vaccination]

Secondary Outcome Measures

Proportion of participants with Seroconversion [on Day 8 (age 55+ only), Day 29, Day 43, Day 71, Day 208 and Day 365.]
Seroconversion is defined as >= 4-fold increase in SARS-CoV-2 neutralizing antibody titer and S-protein binding IgG levels between Day 1 and post-vaccination timepoints
Immune response as determined by the geometric mean titer (GMT) of SARS-CoV-2-specific neutralizing antibodies. [on Day 8 (age 55+ only), Day 29, Day 71, Day 208 and Day 365]
Immune response as determined geometric mean titer (GMT) of IgG antibodies to SARS-CoV-2 S-protein [on Day 8 (age 55+ only), Day 29, Day 43, Day 71, Day 208 and Day 365]
Assessment of T-cell responses (Th1/Th2 polarization) from PBMCs in a subset of participants after in vitro stimulation with SARS-CoV-2 antibodies using, e.g. ELISpot ir intracellular cytokine staining [on Day 1, Day 8, Day 29, Day 43, Day 71, Day 208 and Day 365]
Frequency and severity of solcited injection site and systemic reactions [within 7 days after each and after any vaccination]
Frequency and severity of any Adverse Events (AE) [until Month 12]
Frequency and severity of any unsolicited Adverse Events (AE) [until Day 43]
Frequency and severity of any unsolicited vaccine-related Adverse Events (AE) [until Day 43]
Frequency and severity of any Serious Adverse Event (SAE) [until Month 12]
Frequency and severity of any Adverse Event Of Special Interest (AESI) [until Month 12]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Participants must have read, understood, and signed the informed consent form (ICF).
Participants of either gender aged 12 years and older at screening.
Medically stable
Must be able to attend all visits of the study and comply with all study procedures,
Women of childbearing potential (WOCBP) must be able and willing to use at least 1 highly effective method of contraception for a minimum of 3 months after the last dose of study vaccine.
WOCBPs must have a negative pregnancy test prior to each vaccination.

Exclusion Criteria:

Participant is pregnant or planning to become pregnant within 3 months after study vaccine administration.
History of allergy to any component of the vaccine.
Significant infection (e.g. positive SARS-CoV-2 RT-PCR) or other acute illness, including fever > 100 °F (> 37.8 °C) 48 hours before vaccination.
Participant has a known or suspected defect of the immune system
Participant has a history of cerebral venous sinus thrombosis, heparin-induced thrombocytopenia or antiphospholipid syndrome.
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.
History of drug dependency or current use of drug of abuse or alcohol abuse at screening.
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 randomization (Visit 1).
History of clinically significant bleeding disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
Severe and uncontrolled ongoing autoimmune or inflammatory disease History of Guillain-Barre syndrome or any other demyelinating condition.
Any other significant disease, disorder or finding which in the opinion of the investigator may significantly increase the risk to the volunteer

Prior/concomitant therapy:

Receipt of immunoglobulin or another blood product within the 3 months before expected day of randomization (visit 1) in this study or those who expect to receive immunoglobulin or another blood product during this study.
Receipt of medications and or vaccinations intended to prevent COVID-19.
Receipt of any vaccine (licensed or investigational), other than licensed influenza vaccine, within 28 days prior to the expected day of randomization (Visit 1).
Any member of the study team or sponsor.
An immediate family member or household member of the study's personnel.

Booster Vaccination (Adolescents)

In addition to the above described eligibility criteria, the following criteria must be met:

Participant has completed the primary vaccination schedule per protocol (i.e. has received 2 study vaccinations within protocol windows).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Barnsley Hospital NHS FT	Barnsley	United Kingdom	S75 2EP
2	University Hospitals Birmingham NHS Foundation Trust	Birmingham	United Kingdom	B15 2WB
3	Blackpool Teaching Hospitals NHS Foundation Trust	Blackpool	United Kingdom	FY3 8NR
4	North Bristol NHS Trust	Bristol	United Kingdom	BS10 5NB
5	University Hospitals Bristol and Weston NHS Foundation Trust	Bristol	United Kingdom	BS2 8DX
6	Cambridge Biomedical Research Centre	Cambridge	United Kingdom	CB2 0QQ
7	Cheadle Community Hospital	Cheadle	United Kingdom	ST10 1NS
8	University Hospitals Coventry & Warwickshire	Coventry	United Kingdom	CV2 2DX
9	Western General Hospital, Edinburgh - NHS Lothian	Edinburgh	United Kingdom	EH42XU
10	Epsom and St. Helier University Hospitals NHS Trust	Epsom	United Kingdom	KT187EG
11	Queen Elizabeth University Hospital-Glasgow- NHS Greater Glasgow	Glasgow	United Kingdom	G51 4TF
12	Royal Surrey County Hospital NHS Foundation Trust	Guildford	United Kingdom	GU2 7XX
13	University Hospitals of Leicester NHS Trust	Leicester	United Kingdom	LE39QP
14	NHS Foundation Trust Royal Liverpool University Hospital	Liverpool	United Kingdom	L7 8XP
15	Barts Health NHS Trust	London	United Kingdom	E11BB
16	Panthera London	London	United Kingdom	EN3 4GS
17	Royal Free London NHS Foundation Trust	London	United Kingdom	NW3 2QG
18	King's College Hospital, Trust College HOspital NHS Foundation Trust	London	United Kingdom	SE59RS
19	Chelsea and Westminster Hospital NHS Trust	London	United Kingdom	SW10 9NH
20	St George's University Hospitals NHS Foundation Trust	London	United Kingdom	SW17 0RE
21	NIHR UCLH Clinical Research Facility	London	United Kingdom	W1T 7HA
22	The Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital Newcastle	Newcastle	United Kingdom	NE1 4LP
23	Northumbria Healthcare NHS Foundation Trust - North Tyneside General Hospital	North Shields	United Kingdom	NE29 8NH
24	Lakeside Healthcare Research	Northampton	United Kingdom	NN17 2UR
25	Nottingham University Hospitals NHS Trust	Nottingham	United Kingdom	NG5 1PB
26	University Hospital Plymouth NHS Trust	Plymouth	United Kingdom	PL6 5FP
27	Panthera Biopartners Preston	Preston	United Kingdom	PR1 6YA
28	Panthera Biopartners Manchester	Rochdale	United Kingdom	OL11 4AU
29	Northern Care Alliance NHS Group, Salford Royal NHS Foundation Trust	Salford	United Kingdom	M6 8HD
30	Southampton University Hospitals NHS Trust	Southampton	United Kingdom	SO16 6YD
31	Royal Cornwall Hospitals NHS Trust	Truro	United Kingdom	TR13LJ