Dose Finding Study to Evaluate The Safety, Tolerability and Immunogenicity of an Inactiviated, Adjuvanted SARS-CoV-2 Virus Vaccine Candidate Against Covid-19 in Healthy Subjects

• ClinicalTrials.gov Identifier: NCT04671017
• Recruitment Status: Completed
• First Posted: December 17, 2020
• Results First Posted: March 24, 2022
• Last Update Posted: April 22, 2022
• Sponsor: Valneva Austria GmbH
• Collaborator: National Institute for Health Research, United Kingdom
• Information provided by (Responsible Party): Valneva Austria GmbH

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: SARS-CoV-2 Virus Infection
• Intervention: Biological: VLA2001
• Enrollment: 153

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Period Title: Overall Study
Started	51	51	51
Completed	51	51	51
Not Completed	0	0	0

Baseline Characteristics

Arm/Group Title		Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001	Total
Arm/Group Description		VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	Total of all reporting groups
Overall Number of Baseline Participants		51	51	51	153
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	51 participants	51 participants	51 participants	153 participants
		33.7 (8.89)	35.5 (9.53)	31.3 (8.52)	33.5 (9.10)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	51 participants	51 participants	51 participants	153 participants
	Female	24	17	29	70
	Male	27	34	22	83
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Count of participants	Number Analyzed	51 participants	51 participants	51 participants	153 participants
White		46	51	46	143
Black		0	0	0	0
Asian		1	0	0	1
Mixed		0	0	4	4
Latin		1	0	0	1
Latin American		2	0	0	2
Latino		1	0	0	1
White European		0	0	1	1

Outcome Measures

1. Primary Outcome

Title	Frequency of Solicited AEs (Local and Systemic Reactions) Within 7 Days After Any Vaccination of the Primary Vaccination Series
Description	[Not Specified]
Time Frame	within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	51	51
Measure Type: Number; Unit of Measure: events
Subjects with at least one Solicited Injection Site Reaction	35	31	36
Injection site tenderness	32	23	34
Injection site pain	19	21	24
Injection site itching	3	3	2
Injection site swelling	1	0	1
Subjects with at least one Solicited Systemic Reactions	37	32	37
Headache	28	17	26
Fatigue	23	15	22
Muscle pain	18	15	17
Nausea/Vomiting	5	7	6
Fever/Body temperature	2	0	0

2. Primary Outcome

Title	Geometric Mean Titre (GMT) for Neutralizing Antibodies Against SARS-CoV-2 Determined by Wild-type Virus Neutralizing Assay
Description	[Not Specified]
Time Frame	Day 36

Outcome Measure Data

Analysis Population Description

Overall Number of Participants analyzed according to Per-Protocol Analysis Set. The Per-Protocol Analysis Set includes all participants who have no major protocol deviations. Participants who received an already licensed COVID-19 vaccine outside of the study or participants who received less than 2 vaccinations will be excluded.

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	49	50
Geometric Mean (95% Confidence Interval); Unit of Measure: Geometric Mean Titer
	161.1; (121.35 to 213.82)	222.3; (171.84 to 287.67)	530.4; (421.49 to 667.52)

3. Secondary Outcome

Title	Frequency of Any Unsolicited AE
Description	[Not Specified]
Time Frame	until Day 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	51	51
Measure Type: Number; Unit of Measure: events
Subjects with at least one unsolicited AE	22	17	21
Investigations	10	8	8
Red blood cell sedimentation rate increased	5	4	5
Aspartate aminotransferase increased	2	1	2
Blood bilirubin increased	2	0	2
Haemoglobin decreased	0	0	2
Lymphocyte count decreased	0	1	1
Red blood cells urine	1	1	0
White blood cell count decreased	1	1	0
Alanine aminotransferase increased	0	0	1
Blood sodium decreased	1	0	0
C-reactive protein increased	1	0	0
Neutrophil count decreased	1	0	0
Prothrombin time prolonged	1	0	0
Red blood cell count decreased	0	0	1
White blood cell count increased	0	1	0
Infections and infestations	4	5	2
COVID-19	1	1	0
Gastroenteritis	1	0	1
Tooth infections	0	1	1
Vulvovaginal candidiasis	0	2	0
Epididymitis	0	1	0
Onychomycosis	1	0	0
Paronychia	0	1	0
Urinary tract infections	1	0	0
Blood and lymphatic system disorders	4	2	4
Neutropenia	2	0	3
Lymphopenia	1	1	0
Thrombocytopenia	0	1	1
Eosinophilia	1	0	0
Leukopenia	1	0	0
Microcytic anaemia	1	0	0
Neutrophilia	0	1	0
Nervous system disorders	3	1	3
Headache	0	1	3
Dizziness	1	0	0
Paraesthesia	1	0	0
Presyncope	1	0	0
Respiratory, thoracic and mediastinal disorders	3	3	1
Oropharyngeal pain	3	3	1
Cough	1	0	0
Rhinorrhoea	0	1	0
Sinus congestion	1	0	0
Injury, poisoning and procedural complications	1	2	1
Vaccination complications	1	1	0
Chillblains	0	1	0
Ligament sprain	0	0	1
Gastrointestinal disorders	3	0	0
Aphthous ulcer	1	0	0
Constipation	1	0	0
Diarrhoea	1	0	0
Gingival discomfort	1	0	0
General disorders and administration site conditions	1	1	1
Influenza like illness	0	0	1
Pain	1	0	0
Peripheral swelling	0	1	0
Musculoskeletal and connective tissue disorders	1	2	0
Arthritis	0	1	0
Limb discomfort	0	1	0
Musculoskeletal stiffness	1	0	0
Pain in extremity	1	0	0
Metabolism and nutrition disorders	1	0	1
Dehydration	0	0	1
Increased appetite	1	0	0
Renal and urinary disorders	1	1	0
Haematuria	1	1	0
Reproductive system and breast disorders	1	0	1
Dysmenorrhoea	0	0	1
Vaginal haemorrhage	1	0	0
Eye disorders	0	0	1
Asthenopia	0	0	1
Psychiatric disorders	0	0	1
Anxiety	0	0	1
Skin and subcutaneous tissue disorders	0	0	1
Rash erythematous	0	0	1

4. Secondary Outcome

Title	Frequency of Any Vaccine-related AE
Description	[Not Specified]
Time Frame	until Day 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	51	51
Measure Type: Number; Unit of Measure: events
Subjects with at least one treatment related unsolicited AE until Day 36	12	7	8
Investigations	6	5	4
Red blood cell sedimentation rate increased	5	3	3
Alanine aminotransferase increased	0	0	1
Blood bilirubin increased	1	0	0
Lymphocyte count decreased	0	1	0
White blood cell count decreased	0	1	0
Blood and lymphatic system disorders	2	0	2
Neutropenia	1	0	1
Eosinophilia	1	0	0
Thromocytopenia	0	0	1
Nervous system disorders	2	0	1
Dizziness	1	0	0
Headache	0	0	1
Paraesthesia	1	0	0
Respiratory, thoracic and mediastinial disorders	2	1	0
Oropharyngeal pain	2	1	0
Musculoskeletal and connective tissue disorders	1	1	0
Limb discomfort	0	1	0
Musculoskeletal stiffness	1	0	0
Gastrointestinal disorders	1	0	0
Diarrhoea	1	0	0
General disorders and administration site conditions	1	0	0
Pain	1	0	0
Infections and infestations	0	0	1
Gastroenteritis	0	0	1
Skin and subcutaneous tissue disorders	0	0	1
Rash erythematous	0	0	1

5. Secondary Outcome

Title	Frequency and Severity of Any AE
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Frequency and Severity of Any Vaccine-related AE
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Frequency of Any SAE
Description	All Adverse Events of Special Interest (AESIs) were treated as important medical event and were therefore be treated as SAE according to protocol.
Time Frame	until Day 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	51	51
Measure Type: Number; Unit of Measure: events
	0	1	0

8. Secondary Outcome

Title	Frequency of Any AESI
Description	[Not Specified]
Time Frame	until Day 36

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Low Dose: VLA2001	Medium Dose: VLA2001	High Dose: VLA2001
Arm/Group Description:	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
Overall Number of Participants Analyzed	51	51	51
Measure Type: Number; Unit of Measure: events
	0	1	0

9. Secondary Outcome

Title	Frequency and Severity of Any SAE
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

10. Secondary Outcome

Title	Frequency and Severity of an AESI
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	Frequency and Severy of Solicited AEs (Local and Systemic Reactions) After the Booster Vaccination
Description	[Not Specified]
Time Frame	until Visit 7 plus 6 days

Outcome Measure Data Not Reported

12. Secondary Outcome

Title	Frequency and Severity of Any Unsolicited AE
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

13. Secondary Outcome

Title	Frequency and Severity of Any Vaccine-related AE
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

14. Secondary Outcome

Title	Frequency and Severity of Any SAE
Description	[Not Specified]
Time Frame	until Visit 10

Outcome Measure Data Not Reported

15. Secondary Outcome

Title	Frequency and Severity of Any AESI
Description	[Not Specified]
Time Frame	until Visit 10

Outcome Measure Data Not Reported

16. Secondary Outcome

Title	Immune Response as Measured by Neutralizing Antibody Titres Against SARS-CoV-2
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

17. Secondary Outcome

Title	Proportion of Participants With Seroconversion in Terms of Neutralizing Antibodies
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

18. Secondary Outcome

Title	Fold Increase of SARS-CoV-2 Neutralizing Antibody Titres Compared With Baseline
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

19. Secondary Outcome

Title	GMTs for IgG Antibodies Against SARS-CoV-2 Determined by ELISA
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

20. Secondary Outcome

Title	Proportion of Participants With Seroconversion in Terms of IgG Antibodies Against SARS-CoV-2, as Determined by ELISA in Participants Negative for SARS-CoV-2 at Screening
Description	[Not Specified]
Time Frame	until Day 208

Outcome Measure Data Not Reported

21. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) From Pre-booster Time Point (Visit 7) to 2 Weeks After Booster Dose With Regards to Neutralizing Antibodies
Description	[Not Specified]
Time Frame	until Visit 8

Outcome Measure Data Not Reported

22. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) From Pre-booster Time Point (Visit 7) to 4 Weeks After Booster Dose With Regards to Neutralizing Antibodies
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

23. Secondary Outcome

Title	Proportion of Participants With 4-fold Increase From Pre-booster Time Point (Visit 7) to 2 Weeks After Booster Dose With Regards to Neutralizing Antibodies
Description	[Not Specified]
Time Frame	until Visit 8

Outcome Measure Data Not Reported

24. Secondary Outcome

Title	Proportion of Participants With 4-fold Increase From Pre-booster Time Point (Visit 7) to 4 Weeks After Booster Dose With Regards to Neutralizing Antibodies
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

25. Secondary Outcome

Title	Geometric Mean Titres (GMT) Measured as Neutralizing Antibody Titres Against SARSCoV-2
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

26. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) From Pre-booster Time Point (Visit 7) to 2 Weeks After Booster Dose With Regards to S-protein Binding Antibodies (ELISA)
Description	[Not Specified]
Time Frame	until Visit 8

Outcome Measure Data Not Reported

27. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) From Pre-booster Time Point (Visit 7) to 4 Weeks After Booster Dose With Regards to S-protein Binding Antibodies (ELISA)
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

28. Secondary Outcome

Title	Proportion of Participants With 4-fold Increase From Pre-booster Time Point (Visit 7) to 2 Weeks After Booster Dose in Regards to S-protein Binding Antibodies (ELISA)
Description	[Not Specified]
Time Frame	until Visit 8

Outcome Measure Data Not Reported

29. Secondary Outcome

Title	Proportion of Participants With 4-fold Increase From Pre-booster Time Point (Visit 7) to 4 Weeks After Booster Dose in Regards to S-protein Binding Antibodies (ELISA)
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

30. Secondary Outcome

Title	Geometric Mean Titres (GMT) Measured as IgG Antibodies Against SARS-CoV-2 (ELISA
Description	[Not Specified]
Time Frame	until Visit 9

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Adverse event data was collected from the date of first vaccination until the second part of the study, where participants were followed up on Day 106 (Visit 5) and will be followed up further until Day 208/Month 7 (Visit 6), 6 months after the second vaccination.
Adverse Event Reporting Description	The number of participants here represent the number of healthy adults recruited in 3 dose groups (low, medium and high). Adverse event information was collected at specified time points up to the cut-off date for Day 106 (Visit 5) analysis of 30 June 2021.
Arm/Group Title	Low Dose: VLA2001		Medium Dose: VLA2001		High Dose: VLA2001
Arm/Group Description	VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide		VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide		VLA2001 whole virus inactivated SARS-CoV-2 vaccine adjuvanted with cytosine phospho-guanine (CpG) 1018 in comibinationn with aluminium hydroxide
All-Cause Mortality
	Low Dose: VLA2001		Medium Dose: VLA2001		High Dose: VLA2001
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/51 (0.00%)		0/51 (0.00%)		0/51 (0.00%)
Serious Adverse Events
	Low Dose: VLA2001		Medium Dose: VLA2001		High Dose: VLA2001
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0.00%)		1/51 (1.96%)		0/51 (0.00%)
Injury, poisoning and procedural complications
Chillblains *	0/51 (0.00%)	0	1/51 (1.96%)	1	0/51 (0.00%)	0
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Low Dose: VLA2001		Medium Dose: VLA2001		High Dose: VLA2001
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/51 (15.69%)		6/51 (11.76%)		12/51 (23.53%)
Blood and lymphatic system disorders
Neutropenia *	2/51 (3.92%)		0/51 (0.00%)		3/51 (5.88%)
Investigations
Red blood cell sedimentation rate increased *	5/51 (9.80%)		4/51 (7.84%)		5/51 (9.80%)
Nervous system disorders
Headache †	0/51 (0.00%)		1/51 (1.96%)		3/51 (5.88%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain *	3/51 (5.88%)		3/51 (5.88%)		1/51 (1.96%)
* Indicates events were collected by non-systematic assessment; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Clinical Strategy Manager
• Organization: Valneva Austria GmbH
• Phone: +43 1 206 20 ext 0
• EMail: office@valneva.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lazarus R, Taucher C, Brown C, Corbic Ramljak I, Danon L, Dubischar K, Duncan CJA, Eder-Lingelbach S, Faust SN, Green C, Gokani K, Hochreiter R, Wright JK, Kwon D, Middleditch A, Munro APS, Naker K, Penciu F, Price D, Querton B, Riaz T, Ross-Russell A, Sanchez-Gonzalez A, Wardle H, Warren S, Finn A; Valneva Phase 1 Trial Group. Safety and immunogenicity of the inactivated whole-virus adjuvanted COVID-19 vaccine VLA2001: A randomized, dose escalation, double-blind phase 1/2 clinical trial in healthy adults. J Infect. 2022 Sep;85(3):306-317. doi: 10.1016/j.jinf.2022.06.009. Epub 2022 Jun 16.

• Responsible Party: Valneva Austria GmbH
• ClinicalTrials.gov Identifier: NCT04671017
• Other Study ID Numbers: VLA2001-201
• First Submitted: December 15, 2020
• First Posted: December 17, 2020
• Results First Submitted: March 7, 2022
• Results First Posted: March 24, 2022
• Last Update Posted: April 22, 2022