A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001)

• ClinicalTrials.gov Identifier: NCT04498247
• Recruitment Status: Terminated
• First Posted: August 4, 2020
• Results First Posted: December 23, 2021
• Last Update Posted: December 23, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Coronavirus Disease (COVID-19)
• Interventions: Biological: V591; Other: Placebo
• Enrollment: 263

Participant Flow

Recruitment Details	Healthy adults with no prior history of confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, or known exposure to an individual with confirmed Coronavirus Disease 2019 (COVID-19) or SARS-CoV-2 infection were enrolled in this study.
Pre-assignment Details

Arm/Group Title	V591 1×10^4 TCID50-1 Dose	V591 1×10^5 TCID50-1 Dose	V591 1x10^5 TCID50- 2 Dose	V591 1×10^6 TCID50-1 Dose	V591 1×10^6 TCID50-2 Dose	V591 1×10^7 TCID50	Placebo- 1 Dose	Placebo- 2 Dose
Arm/Group Description	Participants received one dose of V591 1x10^4 tissue culture infectious dose (TCID50) on Day 1	Participants received one dose of V591 1×10^5 TCID50 on Day 1.	Participants received one dose of V591 1×10^5 TCID50 on Day 1 and a second V591 1×10^5 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^6 TCID50 on Day 1	Participants received one dose of V591 1×10^6 TCID50 on Day 1 and a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1	Participants received one dose of placebo on Day 1 and a second dose of placebo on Day 57.
Period Title: Overall Study
Started	21	80	4	81	4	20	51	2
Vaccination 1	20	80	4	81	4	20	51	2
Vaccination 2	0	0	4	0	4	0	0	2
Completed	20	68	4	70	4	20	43	2
Not Completed	1	12	0	11	0	0	8	0
Reason Not Completed
Lost to Follow-up	0	0	0	1	0	0	0	0
Mistakenly Randomized; Not Treated	1	0	0	0	0	0	0	0
Withdrawal by Subject	0	8	0	7	0	0	1	0
Received a non-study COVID-19 vaccine.	0	4	0	3	0	0	7	0

Baseline Characteristics

Arm/Group Title		V591 1×10^4 TCID50-1 Dose	V591 1×10^5 TCID50- 1 Dose	V591 1x10^5 TCID50- 2 Dose	V591 1×10^6 TCID50-1 Dose	V591 1×10^6 TCID50-2 Dose	V591 1×10^7 TCID50	Placebo - 1 Dose	Placebo- 2 Dose	Total
Arm/Group Description		Participants received one dose of V591 1x10^4 TCID50 on Day 1	Participants received one dose of V591 1×10^5 TCID50 on Day 1.	Participants received one dose of V591 1×10^5 TCID50 on Day 1 and a second V591 1×10^5 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^6 TCID50 on Day 1.	Participants received one dose of V591 1×10^6 TCID50 on Day 1 and a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1.	Participants received one dose of placebo on Day 1 and a second dose of placebo on Day 57.	Total of all reporting groups
Overall Number of Baseline Participants		21	80	4	81	4	20	51	2	263
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	21 participants	80 participants	4 participants	81 participants	4 participants	20 participants	51 participants	2 participants	263 participants
		39.7 (10.4)	59.7 (14.8)	45.0 (6.6)	58.4 (15.2)	40.3 (13.2)	26.6 (6.8)	56.2 (17.9)	34.5 (0.7)	53.8 (17.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants	80 participants	4 participants	81 participants	4 participants	20 participants	51 participants	2 participants	263 participants
	Female	9 42.9%	46 57.5%	3 75.0%	43 53.1%	4 100.0%	14 70.0%	27 52.9%	2 100.0%	148 56.3%
	Male	12 57.1%	34 42.5%	1 25.0%	38 46.9%	0 0.0%	6 30.0%	24 47.1%	0 0.0%	115 43.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants	80 participants	4 participants	81 participants	4 participants	20 participants	51 participants	2 participants	263 participants
	Hispanic or Latino	1 4.8%	20 25.0%	0 0.0%	12 14.8%	1 25.0%	0 0.0%	3 5.9%	0 0.0%	37 14.1%
	Not Hispanic or Latino	20 95.2%	60 75.0%	4 100.0%	69 85.2%	3 75.0%	20 100.0%	48 94.1%	2 100.0%	226 85.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	21 participants	80 participants	4 participants	81 participants	4 participants	20 participants	51 participants	2 participants	263 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	1 1.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.0%	0 0.0%	2 0.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	2 2.5%	0 0.0%	3 3.7%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	5 1.9%
	White	19 90.5%	77 96.3%	4 100.0%	78 96.3%	4 100.0%	20 100.0%	50 98.0%	2 100.0%	254 96.6%
	More than one race	2 9.5%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 0.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least One Solicited Injection Site Adverse Event (AE) After Any Study Intervention
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Injection site AEs of pain/tenderness, swelling, and redness/erythema were assessed.
Time Frame	Up to 5 days after any study intervention

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		25.0	6.0	15.3	55.0	7.5
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			0.0	25.0		0.0

2. Primary Outcome

Title	Percentage of Participants With at Least One Solicited Systemic AE After Any Study Intervention
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Systemic AEs of fever, muscle pain, joint pain, headache, fatigue, rash, or nausea were assessed.
Time Frame	Up to 14 days after any study intervention

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		50.0	45.2	37.6	65.0	56.6
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			25.0	75.0		50.0

3. Primary Outcome

Title	Percentage of Participants With at Least One Unsolicited Adverse Event After Any Study Intervention
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. All unsolicited AEs were assessed.
Time Frame	Up to 28 days after any study intervention

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		55.0	34.5	32.9	70.0	37.7
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			0.0	25.0		0.0

4. Primary Outcome

Title	Percentage of Participants With at Least 1 Serious Adverse Event
Description	An SAE is defined as any untoward medical occurrence that at any dose, results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
Time Frame	Up to 56 days after vaccination 1 and up to 122 days after vaccination 2 (up to 178 days)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of Participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		0.0	0.0	2.4	0.0	1.9
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			0.0	0.0		0.0

5. Primary Outcome

Title	Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time Frame	Up to 57 days

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of Participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		5.0	6.0	4.7	0	5.7
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			0.0	0.0		0.0

6. Primary Outcome

Title	Percentage of Participants With at Least 1 Medically Attended Adverse Event (MAAE)
Description	A MAAE is defined as an adverse event in which medical attention is received during an unscheduled, non-routine outpatient visit, such as an emergency room visit, office visit, or an urgent care visit with any medical personnel for any reason.
Time Frame	Up to 56 days after vaccination 1 and up to 122 days after vaccination 2 (up to 178 days)

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study intervention and received the dose relevant to the data collection time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Measure Type: Number; Unit of Measure: Percentage of Participants
Following Vaccination 1	Number Analyzed	20 participants	84 participants	85 participants	20 participants	53 participants
		30.0	10.7	11.8	40.0	9.4
Following Vaccination 2	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			0.0	0.0		0.0

7. Secondary Outcome

Title	Geometric Mean Titers for Serum Neutralizing Antibodies (nAb) as Measured by Pseudo-virus Neutralization Assay (PNA)
Description	Serum samples were collected and the titers of serum neutralization antibodies were assessed using PNA. Geometric mean titers were calculated using a constrained longitudinal data analysis (cLDA) method where the response vector consisted of the log transformed pre-vaccination and post-vaccination antibody titers. The point estimates were calculated by exponentiating the estimates of the mean of the natural log values; and the within-group 95% confidence intervals (CIs) were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.
Time Frame	Days 1, 15, 29, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint, and who had available data at the indicated time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose. Data were not collected for planned timepoints on days 115, 211, 365, 422, and 534 due to early termination.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Geometric Mean (95% Confidence Interval); Unit of Measure: Titer
Day 1	Number Analyzed	20 participants	84 participants	84 participants	20 participants	51 participants
		5.0; (5.0 to 5.0)	6.3; (5.1 to 7.8)	5.9; (5.0 to 6.9)	9.1; (5.0 to 16.7)	5.0; (5.0 to 5.0)
Day 15	Number Analyzed	19 participants	84 participants	78 participants	20 participants	47 participants
		5.8; (4.2 to 8.1)	6.7; (5.3 to 8.5)	7.9; (6.1 to 10.4)	53.1; (17.2 to 164.6)	5.3; (4.7 to 6.1)
Day 29	Number Analyzed	20 participants	79 participants	81 participants	20 participants	50 participants
		5.0; (5.0 to 5.0)	8.3; (6.0 to 11.3)	8.3; (6.3 to 11.0)	31.2; (11.2 to 86.7)	6.3; (4.8 to 8.1)
Day 57	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			13.7 [1]; (NA to NA)	5.0 [1]; (NA to NA)		5.0 [1]; (NA to NA)
Day 71	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			25.7 [1]; (NA to NA)	45.2 [1]; (NA to NA)		5.0 [1]; (NA to NA)
Day 85	Number Analyzed	0 participants	4 participants	3 participants	0 participants	2 participants
			24.6 [1]; (NA to NA)	54.2 [1]; (NA to NA)		5.0 [1]; (NA to NA)

[1]

The 95% confidence interval is not provided when n is less than 5 participants.

8. Secondary Outcome

Title	Geometric Mean Concentration of Total Anti-Spike Immunoglobulin G (IgG) Antibodies as Measured by Enzyme-Linked Immunosorbent Assay (ELISA)
Description	Serum samples were collected and the concentrations of total anti-spike IgG antibodies were assessed using ELISA. Geometric mean concentrations were calculated using a cLDA method where the response vector consisted of the log transformed pre-vaccination and post-vaccination antibody titers. The point estimates were calculated by exponentiating the estimates of the mean of the natural log values; and the within-group 95% confidence intervals (CIs) were obtained by exponentiating the CIs of the mean of the natural log values based on the t-distribution.
Time Frame	Days 1, 15, 29, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint, and who had available data at the indicated time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose. Data were not collected for planned timepoints on days 115, 211, 365, 422, and 534 due to early termination.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Geometric Mean (95% Confidence Interval); Unit of Measure: ELISA unit/mL
Day 1	Number Analyzed	20 participants	84 participants	82 participants	20 participants	51 participants
		25.2; (25.2 to 25.2)	33.9; (26.1 to 44.0)	36.3; (28.2 to 46.9)	46.3; (24.7 to 86.8)	26.1; (24.8 to 27.5)
Day 15	Number Analyzed	19 participants	84 participants	76 participants	20 participants	47 participants
		26.2; (24.1 to 28.5)	35.7; (27.2 to 46.7)	41.6; (30.0 to 57.6)	239.2; (78.8 to 725.9)	26.4; (24.7 to 28.2)
Day 29	Number Analyzed	20 participants	79 participants	79 participants	20 participants	50 participants
		28.6; (23.7 to 34.6)	44.0; (31.6 to 61.3)	52.6; (36.6 to 75.6)	294.8; (110.3 to 788.2)	31.5; (25.3 to 39.3)
Day 57	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			97.7 [1]; (NA to NA)	25.2 [1]; (NA to NA)		25.2 [1]; (NA to NA)
Day 71	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			184.7 [1]; (NA to NA)	336.1 [1]; (NA to NA)		25.2 [1]; (NA to NA)
Day 85	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			180.8 [1]; (NA to NA)	260.6 [1]; (NA to NA)		25.2 [1]; (NA to NA)

[1]

The 95% confidence interval is not provided when n is less than 5 participants.

9. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) for Serum nAb as Measured by PNA
Description	Serum samples were collected and the titers of serum neutralization antibodies were assessed using PNA. Geometric mean titers were calculated using a cLDA method where the response vector consisted of the log transformed pre-vaccination and post-vaccination antibody titers. GMFR is defined as the geometric mean of the ratio of concentration at specified timepoints after vaccination divided by concentration at baseline (Day 1).
Time Frame	Days 1, 15, 29, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint, and who had available data at the indicated time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose. Data were not collected for planned timepoints on days 115, 211, 365, 422, and 534 due to early termination.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Geometric Mean (95% Confidence Interval); Unit of Measure: Ratio
Day 15	Number Analyzed	19 participants	84 participants	78 participants	20 participants	47 participants
		1.1; (0.9 to 1.4)	1.0; (1.0 to 1.1)	1.2; (1.1 to 1.5)	4.1; (2.0 to 8.3)	1.1; (0.9 to 1.2)
Day 29	Number Analyzed	20 participants	79 participants	81 participants	20 participants	50 participants
		1.0; (1.0 to 1.0)	1.2; (1.0 to 1.5)	1.3; (1.1 to 1.6)	2.6; (1.2 to 5.5)	1.2; (1.0 to 1.5)
Day 57	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			2.3 [1]; (NA to NA)	1.0 [1]; (NA to NA)		1.0 [1]; (NA to NA)
Day 71	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			3.6 [1]; (NA to NA)	4.5 [1]; (NA to NA)		1.0 [1]; (NA to NA)
Day 85	Number Analyzed	0 participants	4 participants	3 participants	0 participants	2 participants
			3.5 [1]; (NA to NA)	5.4 [1]; (NA to NA)		1.0 [1]; (NA to NA)

[1]

The 95% confidence interval is not provided when n is less than 5 participants.

10. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of Total Anti-Spike IgG Antibodies as Measured by ELISA
Description	Serum samples were collected and the total anti-spike IgG antibodies assessed using ELISA. Geometric mean concentrations were calculated using a cLDA method where the response vector consisted of the log transformed pre-vaccination and post-vaccination antibody titers. GMFR is defined as the geometric mean of the ratio of concentration at specified timepoints after vaccination divided by concentration at baseline (Day 1).
Time Frame	Days 1, 15, 29, 57, 71, and 85

Outcome Measure Data

Analysis Population Description

All randomized participants without deviations from the protocol that may substantially affect the results of the immunogenicity endpoint, and who had available data at the indicated time point. Participants were pooled by dose of study intervention administered due to the study's termination prior to most participants receiving their planned second dose. Data were not collected for planned timepoints on days 115, 211, 365, 422, and 534 due to early termination.

Arm/Group Title		V591 1×10^4 TCID50	V591 1×10^5 TCID50	V591 1×10^6 TCID50	V591 1×10^7 TCID50	Placebo
Arm/Group Description:		Participants received one dose of V591 1x10^4 TCID50 on Day 1	All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.	All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.	Participants received one dose of V591 1×10^7 TCID50 on Day 1	Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.
Overall Number of Participants Analyzed		20	84	85	20	53
Geometric Mean (95% Confidence Interval); Unit of Measure: Ratio
Day 15	Number Analyzed	19 participants	84 participants	76 participants	20 participants	47 participants
		1.0; (1.0 to 1.0)	1.0; (1.0 to 1.1)	1.1; (1.0 to 1.3)	3.5; (1.8 to 6.9)	1.0; (0.9 to 1.0)
Day 29	Number Analyzed	20 participants	79 participants	79 participants	20 participants	50 participants
		1.1; (1.0 to 1.2)	1.2; (1.0 to 1.4)	1.3; (1.1 to 1.6)	3.9; (1.8 to 8.6)	1.2; (1.0 to 1.4)
Day 57	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			3.3 [1]; (NA to NA)	1.0 [1]; (NA to NA)		1.0 [1]; (NA to NA)
Day 71	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			5.2 [1]; (NA to NA)	6.7 [1]; (NA to NA)		1.0 [1]; (NA to NA)
Day 85	Number Analyzed	0 participants	4 participants	4 participants	0 participants	2 participants
			5.1 [1]; (NA to NA)	5.2 [1]; (NA to NA)		1.0 [1]; (NA to NA)

[1]

The 95% confidence interval is not provided when n is less than 5 participants.

Adverse Events

Time Frame

Serious adverse events and all cause mortality were collected throughout the duration of the study (up to day 178). Non-serious adverse events were assessed up to day 146.

Adverse Event Reporting Description

The analysis population for all cause mortality consists of all randomized participants. The analysis populations for serious and non-serious adverse events include all randomized participants who received at least one dose of study intervention. Adverse events were reported separately by occurrence after the first dose of study intervention or second dose of study intervention.

Arm/Group Title

V591 1x10⁴ TCID₅₀-Post Vaccination (Vacc) 1

V591 1x10⁵ TCID₅₀-Post Vacc 1

V591 1x10⁶ TCID₅₀-Post Vacc 1

V591 1x10⁷ TCID₅₀-Post Vacc 1

Placebo-Post Vacc 1

V591 1x10⁵ TCID₅₀-Post Vacc 2

V591 1x10⁶ TCID₅₀-Post Vacc 2

Placebo-Post Vacc 2

Arm/Group Description

Participants received one dose of 1x10^4 TCID50 V591 on Day 1

All participants received one dose of V591 1×10^5 TCID50 on Day 1; Some participants received a second V591 1×10^5 TCID50 dose on Day 57.

All participants received one dose of V591 1×10^6 TCID50 on Day 1; Some participants received a second V591 1×10^6 TCID50 dose on Day 57.

Participants received one dose of V591 1×10^7 TCID50 on Day 1

Participants received one dose of placebo on Day 1; Some participants received a second dose of placebo on Day 57.

All participants received 2 doses of V591; one dose of V591 1×10^5 TCID50 on Day 1 and a second dose of V591 1×10^5 TCID50 on Day 57.

All participants received 2 doses of V591; one dose of V591 1×10^6 TCID50 on Day 1 and a second dose of V591 1×10^6 TCID50 on Day 57.

All participants received 2 doses of placebo; one dose of placebo on Day 1 and a second dose of placebo on Day 57.

All-Cause Mortality

V591 1x10⁴ TCID₅₀-Post Vaccination (Vacc) 1

V591 1x10⁵ TCID₅₀-Post Vacc 1

V591 1x10⁶ TCID₅₀-Post Vacc 1

V591 1x10⁷ TCID₅₀-Post Vacc 1

Placebo-Post Vacc 1

V591 1x10⁵ TCID₅₀-Post Vacc 2

V591 1x10⁶ TCID₅₀-Post Vacc 2

Placebo-Post Vacc 2

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

0/21 (0.00%)

0/84 (0.00%)

0/85 (0.00%)

0/20 (0.00%)

0/53 (0.00%)

0/4 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

Serious Adverse Events

V591 1x10⁴ TCID₅₀-Post Vaccination (Vacc) 1

V591 1x10⁵ TCID₅₀-Post Vacc 1

V591 1x10⁶ TCID₅₀-Post Vacc 1

V591 1x10⁷ TCID₅₀-Post Vacc 1

Placebo-Post Vacc 1

V591 1x10⁵ TCID₅₀-Post Vacc 2

V591 1x10⁶ TCID₅₀-Post Vacc 2

Placebo-Post Vacc 2

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

0/20 (0.00%)

0/84 (0.00%)

2/85 (2.35%)

0/20 (0.00%)

1/53 (1.89%)

0/4 (0.00%)

0/4 (0.00%)

0/2 (0.00%)

Cardiac disorders

Coronary artery disease † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

1/85 (1.18%)

1

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Myocardial infarction † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

1/85 (1.18%)

1

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Infections and infestations

COVID-19 † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

1/85 (1.18%)

1

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Nervous system disorders

Migraine † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

0/85 (0.00%)

0

0/20 (0.00%)

0

1/53 (1.89%)

1

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

5%

V591 1x10⁴ TCID₅₀-Post Vaccination (Vacc) 1

V591 1x10⁵ TCID₅₀-Post Vacc 1

V591 1x10⁶ TCID₅₀-Post Vacc 1

V591 1x10⁷ TCID₅₀-Post Vacc 1

Placebo-Post Vacc 1

V591 1x10⁵ TCID₅₀-Post Vacc 2

V591 1x10⁶ TCID₅₀-Post Vacc 2

Placebo-Post Vacc 2

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

15/20 (75.00%)

47/84 (55.95%)

41/85 (48.24%)

20/20 (100.00%)

35/53 (66.04%)

1/4 (25.00%)

3/4 (75.00%)

1/2 (50.00%)

Gastrointestinal disorders

Nausea † 1

3/20 (15.00%)

6

7/84 (8.33%)

9

2/85 (2.35%)

2

4/20 (20.00%)

4

7/53 (13.21%)

8

0/4 (0.00%)

0

1/4 (25.00%)

1

0/2 (0.00%)

0

Vomiting † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

0/85 (0.00%)

0

2/20 (10.00%)

2

1/53 (1.89%)

1

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

General disorders

Fatigue † 1

8/20 (40.00%)

14

22/84 (26.19%)

30

19/85 (22.35%)

25

8/20 (40.00%)

13

20/53 (37.74%)

26

1/4 (25.00%)

1

2/4 (50.00%)

2

0/2 (0.00%)

0

Injection site movement impairment † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

0/85 (0.00%)

0

2/20 (10.00%)

2

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Injection site pain † 1

5/20 (25.00%)

5

6/84 (7.14%)

6

13/85 (15.29%)

14

11/20 (55.00%)

11

4/53 (7.55%)

4

0/4 (0.00%)

0

1/4 (25.00%)

1

0/2 (0.00%)

0

Injection site erythema † 1

0/20 (0.00%)

0

2/84 (2.38%)

2

2/85 (2.35%)

2

0/20 (0.00%)

0

0/53 (0.00%)

0

1/4 (25.00%)

1

0/4 (0.00%)

0

0/2 (0.00%)

0

Puncture site haematoma † 1

0/20 (0.00%)

0

0/84 (0.00%)

0

0/85 (0.00%)

0

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

1/4 (25.00%)

1

0/2 (0.00%)

0

Infections and infestations

COVID-19 † 1

0/20 (0.00%)

0

9/84 (10.71%)

9

8/85 (9.41%)

8

0/20 (0.00%)

0

5/53 (9.43%)

5

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Injury, poisoning and procedural complications

Exposure to SARS-CoV-2 † 1

2/20 (10.00%)

2

3/84 (3.57%)

3

4/85 (4.71%)

4

2/20 (10.00%)

2

4/53 (7.55%)

4

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Investigations

Blood creatine phosphokinase increased † 1

1/20 (5.00%)

1

1/84 (1.19%)

1

1/85 (1.18%)

1

2/20 (10.00%)

2

1/53 (1.89%)

1

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Musculoskeletal and connective tissue disorders

Arthralgia † 1

2/20 (10.00%)

3

8/84 (9.52%)

10

7/85 (8.24%)

8

1/20 (5.00%)

1

7/53 (13.21%)

8

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Back pain † 1

2/20 (10.00%)

4

3/84 (3.57%)

3

0/85 (0.00%)

0

1/20 (5.00%)

1

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Myalgia † 1

3/20 (15.00%)

5

14/84 (16.67%)

15

14/85 (16.47%)

15

3/20 (15.00%)

3

10/53 (18.87%)

14

0/4 (0.00%)

0

1/4 (25.00%)

2

0/2 (0.00%)

0

Nervous system disorders

Dizziness † 1

1/20 (5.00%)

1

0/84 (0.00%)

0

0/85 (0.00%)

0

2/20 (10.00%)

2

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Headache † 1

4/20 (20.00%)

6

24/84 (28.57%)

34

20/85 (23.53%)

31

9/20 (45.00%)

16

19/53 (35.85%)

22

0/4 (0.00%)

0

2/4 (50.00%)

3

1/2 (50.00%)

1

Anosmia † 1

0/20 (0.00%)

0

5/84 (5.95%)

5

1/85 (1.18%)

1

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Dysgeusia † 1

0/20 (0.00%)

0

5/84 (5.95%)

5

3/85 (3.53%)

3

0/20 (0.00%)

0

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Reproductive system and breast disorders

Dysmenorrhoea † 1

2/20 (10.00%)

2

0/84 (0.00%)

0

0/85 (0.00%)

0

0/20 (0.00%)

0

1/53 (1.89%)

1

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Respiratory, thoracic and mediastinal disorders

Oropharyngeal pain † 1

1/20 (5.00%)

1

1/84 (1.19%)

1

2/85 (2.35%)

2

2/20 (10.00%)

2

3/53 (5.66%)

3

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

Skin and subcutaneous tissue disorders

Rash † 1

2/20 (10.00%)

3

0/84 (0.00%)

0

2/85 (2.35%)

2

1/20 (5.00%)

1

0/53 (0.00%)

0

0/4 (0.00%)

0

0/4 (0.00%)

0

0/2 (0.00%)

0

1 Term from vocabulary, MedDRA 23.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

The study was terminated based on an interim assessment of immunogenicity indicating that V591 was not predicted to provide adequate protection against disease caused by SARS-CoV-2.

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.

If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

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

Vanhoutte F, Liu W, Wiedmann RT, Haspeslagh L, Cao X, Boundy K, Aliprantis A, Davila M, Hartzel J, Li J, McGuire M, Ramsauer K, Tomberger Y, Tschismarov R, Brown DD, Xu W, Sachs JR, Russell K, Stoch SA, Lai E. Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial. EBioMedicine. 2022 Jan;75:103811. doi: 10.1016/j.ebiom.2021.103811. Epub 2022 Jan 15.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT04498247
• Other Study ID Numbers: V591-001; 2020-003493-46 ( EudraCT Number ); V591-001 ( Other Identifier: Merck )
• First Submitted: August 3, 2020
• First Posted: August 4, 2020
• Results First Submitted: December 20, 2021
• Results First Posted: December 23, 2021
• Last Update Posted: December 23, 2021