A double-blind, randomized, multicenter, controlled study to evaluate the immunogenicity, safety, and tolerability of varicella vaccine (VARIVAX™) passage extension 34 (PE34) process administered concomitantly with measles, mumps, and rubella vaccine (M-M-R™ II)

Figures & data

Figure 1. Participant disposition

*Some participants may have discontinued from study vaccine but remained in the trial and completed all study visits.

Table 1. Demographics

	VAR-PE (N = 300)		VAR (N = 300)
	n	(%)	n	(%)
Gender
Male	147	(49.0)	173	(57.7)
Female	153	(51.0)	127	(42.3)
Age (months)
Mean (SD)	13.0 (1.4)		13.2 (1.7)
Median	12.0		12.0
Range	12 to 19		12 to 23
Race
White	237	(79.0)	239	(79.7)
Black	35	(11.7)	23	(7.7)
Other^†	28	(9.3)	38	(12.7)

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

† = Asian, multi-racial, Native American, or Pacific Islander

N = Number of participants randomized in the vaccination group

n = Number of participants in each category

SD = Standard deviation

Table 2. Summary of VZV response rates and geometric mean titers (GMTs) at 6 weeks postdose 1

	VAR-PE (N = 299)		VAR (N = 300)
Parameter	n	Observed Response (95% CI)	n	Observed Response (95% CI)	Risk Difference^†/GMT Ratio^‡ (95% CI)	Conclusion
% ≥5 gpELISA units/mL	245	98.4% (95.9, 99.6)	239	98.3% (95.8, 99.5)	0.0 (−2.7, 2.8)	Non-inferior P < .001
GMT		18.5 (17.1, 20.1)		19.0 (17.6, 20.5)	1.0 (0.9, 1.1)	Non-inferior P < .001

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

† Risk difference = VAR-PE – VAR. The 2-sided 95% CI is based on the natural log-transformed titers and the t-distribution. The conclusion of non-inferiority (similarity) is based on the lower bound of the 2-sided 95% CI for the GMT ratio being > 0.67, which corresponds to a one-sided p-value < 0.025.

‡ GMT ratio = VAR-PE/VAR. The 2-sided 95% CI is based on the natural log-transformed titers and the t-distribution. The conclusion of non-inferiority (similarity) is based on the lower bound of the 2-sided 95% CI for the GMT ratio being > 0.67, which corresponds to a one-sided p-value < 0.025.

N = Number of participants vaccinated in the vaccination group at Dose 1

n = Number of participants with seronegative antibody titer (<1.25gpELISA units/mL) at baseline and postvaccination serology contributing to the per-protocol analysis

gpELISA = Glycoprotein enzyme-linked immunosorbent assay

VZV = Varicella-zoster virus

CI = Confidence interval

GMT = Geometric mean titer

VZV = varicella-zoster virus

Table 3. Adverse Experience (AE) Summary (Days 1 to 42 Postdose 1 and 2)

	VAR-PE (N = 300)		VAR (N = 300)
Parameter	n	(%)	n	(%)
Postdose 1
Participants with follow-up	299		300
With one or more AE	247	(82.6)	240	(80.0)
With vaccine-related* AEs	138	(46.2)	135	(45.0)
Injection-site AEs^†	101	(33.8)	97	(32.3)
Systemic AEs^†	69	(23.1)	66	(22.0)
With serious AEs	3	(1.0)	0	(0.0)
Serious vaccine-related AEs	0	(0.0)	0	(0.0)
Who died^‡	0	(0.0)	0	(0.0)
Discontinued due to an AE	0	(0.0)	0	(0.0)
Postdose 2
Participants with follow-up	276		282
With one or more AE	191	(69.2)	188	(66.7)
With vaccine-related* AEs	95	(34.4)	94	(33.3)
Injection-site AEs^†	78	(28.3)	78	(27.7)
Systemic AEs^†	28	(10.1)	33	(11.7)
With serious AEs	1	(0.4)	1	(0.4)
Serious vaccine-related AEs	0	(0.0)	0	(0.0)
Who died^‡	0	(0.0)	0	(0.0)
Discontinued due to an AE	0	(0.0)	0	(0.0)

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

*Determined by the investigator to be possibly, probably, or definitely related to the vaccine

†Includes those adverse experiences occurring with an overall incidence of 5% or more in the study population

‡No Subject died throughout the course of this study

N = Number of participants randomized and vaccinated in the vaccination group

n = Number of participants in each category

The same subject may appear in different categories, but counted only once in each category

Table 4. Summary of participants with VRC-solicited injection site varicella vaccine related adverse events

	VAR-PE		VAR
	n	(%)	n	(%)
Days 1 to 5 Postdose 1
Participants with follow-up	299		300
with ≥1 VRC-solicited injection-site AE	66	(22.1)	63	(21.0)
Erythema	29	(9.7)	32	(10.7)
Pain	40	(13.4)	38	(12.7)
Swelling	9	(3.0)	17	(5.7)
Days 1 to 5 Postdose 2
Participants with follow-up	276		282
with ≥1 VRC-solicited injection-site AE	70	(25.4)	71	(25.2)
Erythema	54	(19.6)	56	(19.9)
Pain	24	(8.7)	29	(10.3)
Swelling	28	(10.1)	23	(8.2)

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

VRC = vaccine report card

Table 5. Summary of Participants with Systemic Adverse Events (incidence ≥10% in either group)

	VAR-PE		VAR
	n	%	n	%
Days 1 to 42 Postdose 1
Participants with follow-up	299		300
with ≥1 systemic AE	229	76.6	223	74.3
Pyrexia	70	23.4	51	17.0
Irritability	38	12.7	40	13.3
Cough	36	12.0	43	14.3
Rhinorrhea	33	11.0	32	10.7
Otitis media	30	10.0	13	4.3
Upper respiratory tract infection	24	8.0	30	10.0
Diarrhea	22	7.4	44	14.7
Teething	21	7.0	36	12.0
Nasopharyngitis	21	7.0	31	10.3
Days 1 to 42 Postdose 2
Participants with follow-up	276		282
with ≥1 systemic AE	168	60.9	168	59.6
Pyrexia	44	15.9	34	12.1
Rhinorrhea	28	10.1	16	5.7

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

Table 6. Analysis of rates of fever by Day Range between vaccination groups (all participants as treated population)

Day Range		VAR-PE	VAR	Risk Difference(95% CI) ^†
Days 1 to 42 Postdose 1		N = 299	N = 300
Days 1 to 5	Participants with Temperature Follow-Up	297	296
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	6 (2.0%)	3 (1.0%)	1.0 (−1.2, 3.4)
Days 6 to 14	Participants with Temperature Follow-Up	291	295
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	13 (4.5%)	15 (5.1%)	−0.6 (−4.3, 3.0)
Days 15 to 28	Participants with Temperature Follow-Up	290	291
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	11 (3.8%)	10 (3.4%)	0.4 (−2.9, 3.6)
Days 29 to 42	Participants with Temperature Follow-Up	285	286
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	10 (3.5%)	6 (2.1%)	1.4 (−1.4, 4.5)
Days 1 to 42 Postdose 2		N = 276	N = 282
Days 1 to 5	Participants with Temperature Follow-Up	265	282
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	1 (0.4%)	3 (1.1%)	−0.7 (−2.9, 1.1)
Days 6 to 14	Participants with Temperature Follow-Up	269	273
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	6 (2.2%)	3 (1.1%)	1.1(−1.2, 3.8)
Days 15 to 28	Participants with Temperature Follow-Up	265	275
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	8 (3.0%)	6 (2.2%)	0.8 (−2.1, 3.9)
Days 29 to 42	Participants with Temperature Follow-Up	259	274
	Max Temp (oral equivalent): ≥102.2 °F [≥39.0°C]	10 (3.9%)	6 (2.2%)	1.7 (−1.3, 5.0)

VAR-PE = Varicella vaccine PE + measles-mumps-rubella vaccine.

VAR = Varicella vaccine CP2016 + measles-mumps-rubella vaccine

^†The 2-sided 95% CI is calculated using the Miettinen and Nurminen unconditional asymptotic method.