A randomized open-labeled study to demonstrate the non-inferiority of purified chick-embryo cell rabies vaccine administered in the Zagreb regimen (2-1-1) compared with the Essen regimen in Chinese adults

Figures & data

Table 1. Baseline Demographic Characteristics of the Study Population

	Overall population			Immunogenicity subset (Parent study; PPS)			Extension study (FAS)
	Zagreb group (n = 549)	Essen group (n = 275)	P value	Zagreb group (n = 69)	Essen group (n = 70)	P value	Zagreb group (n = 104)	Essen group (n = 96)	P value
Age, mean (SD), years	38.2 ± 7.1	39.3 ± 6.9	0.24	38.5 ± 7.2	40.5 ± 6.3	0.09	39.5 ± 7.3	41.4 ± 6.5	0.054
Weight, mean (SD), kg	68.2 ± 10.9	68.9 ± 11.7	0.39	68.2 ± 10.5	71.9 ± 13.4	0.07	—	—	—
Height, mean (SD), cm	162.7 ± 7.4	162.4 ± 8.2	0.63	163.4 ± 7.6	165.0 ± 9.1	0.28	—	—	—
Males, n (%)	226 (41.4)	121 (44.0)	0.44	28 (41.1)	37 (56.9)	0.15	65 (62.5)	54 (56.25)	0.37
Asian, n (%)	549 (100)	275 (100)	1.0	69 (100)	70 (100)	1.0	104 (100)	96 (100)	1.0

PPS: per protocol set; FAS: full analysis set.

Figure 1. Flow diagram of the trial.

Figure 2. Rabies virus neutralizing antibody concentrations (GMC) in the Zagreb and Essen groups (PP set) on Days 7, 14, 42, and Month 13. Error bars and values in parenthesis represent 95% CI. *Dotted reference line: the WHO recommends a specific antibody level of 0.5 IU/ml as being indicative of an adequate immune response after vaccination.

Figure 3. Rates of seroconversion (defined as RVNA ≥ 0.5 IU/mL) in the Zagreb and Essen groups (PP set) on Days 7, 14, 42, and Month 13 month. Error bars and values in parenthesis represent 95% CI.

Table 2. Local and systemic reactions occurring in the Zagreb and Essen groups after the first vaccination and during the whole trial duration

	After First Vaccination		During the Whole Trial
	Zagreb group (n = 549)	Essen group (n = 275)	Zagreb group (n = 549)	Essen group (n = 275)	P value
Local AEs, any, n (%)			483 (87.9)	241 (87.6)	0.88
Local AEs, n (%)
Erythema	31 (5.7)	10 (3.6)
Mild	0 (0.0)	1 (0.4)	37 (6.7)	17 (6.2)
Moderate			0 (0.0)	1 (0.4)
Swelling
Mild	18 (3.3)	11 (4.0)	42 (7.7)	38 (13.8)
Pain
Mild	392 (71.4)	180 (65.5)	443 (80.7)	215 (78.2)
Moderate	17 (3.1)	4 (1.5)	32 (5.8)	20 (7.3)
Severe	0 (0.0)	0 (0.0)	0 (0.0)	1 (0.4)
Systemic AEs, any, n (%)			177 (32.2)	103 (37.4)	0.13
Systemic AEs, n (%)
Fever
Mild	75 (13.7)	46 (16.7)	106 (19.3)	58 (21.1)
Moderate	11 (2.0)	5 (1.8)	17 (3.1)	10 (3.6)
Severe	1 (0.2)	0 (0.0)	1 (0.2)	0 (0.0)
Shivering
Mild	9 (1.6)	3 (1.1)	18 (3.3)	8 (2.9)
Moderate	1 (0.2)	0 (0.0)	1 (0.2)	0 (0.0)
Severe	0 (0.0)	0 (0.0)	2 (0.4)	0 (0.0)
Malaise
Mild	23 (4.2)	1 (0.4)	34 (6.2)	16 (5.8)
Moderate	1 (0.2)	0 (0.0)	1 (0.2)	1 (0.4)
Headache
Mild	44 (8.0)	16 (5.8)	84 (15.3)	44 (16.0)
Moderate	4 (0.7)	3 (1.1)	7 (1.3)	5 (1.8)
Nausea
Mild	14 (2.5)	8 (2.9)	26 (4.7)	24 (8.7)
Moderate	0 (0.0)	0 (0.0)	2 (0.4)	0 (0.0)
Myalgia
Mild	9 (1.6)	0 (0.0)	24 (4.4)	20 (7.3)
Moderate	2 (0.4)	0 (0.0)	4 (0.7)	3 (1.1)
Severe	0 (0.0)	0 (0.0)	1 (0.2)	0 (0.0)
Arthralgia
Mild	5 (0.9)	1 (0.4)	11 (2.0)	12 (4.4)
Moderate	2 (0.4)	0 (0.0)	2 (0.4)	1 (0.4)
Fatigue
Mild	26 (4.7)	12 (4.4)	57 (10.4)	34 (12.4)
Moderate	2 (0.4)	0 (0.0)	4 (0.7)	0 (0.0)
Rash
Mild	0 (0.0)	0 (0.0)	3 (0.5)	3 (1.1)

Table 3. Incidence of all adverse events occurring in the Zagreb and Essen groups during the trial

Type of reaction	Zagreb group (n = 549)	Essen group (n = 275)	P value
AEs, any, n (%)	102 (18.6)	51 (18.6)	0.99#
AEs possibly or probably related to the vaccine, n (%)	6 (1.1)	9 (3.3)	0.03#
AEs leading to discontinuation, n (%)	1 (0.2)	1 (0.4)	1.00*
SAEs, n (%)	0	1 (0.4)	0.33*

AE = adverse event; SAE = Serious AE.

# Chi-Square test.

*P value was determined by Fisher exact probability method.