Immunogenicity and safety of a booster dose of the hepatitis B vaccine HepB-CpG (HEPLISAV-B®) compared with HepB-Eng (Engerix-B®) and HepB-AS04 (Fendrix®) in adults receiving hemodialysis who previously received hepatitis B vaccination and are not seroprotected: Results of a randomized, multicenter phase 3 study

Figures & data

Figure 1. Patient disposition.

Table 1. Demographics and baseline characteristics (safety population).

Characteristic	HepB-CpG (N = 54)	HepB-Eng (N = 50)	HepB-AS04 (N = 51)	Total (N = 155)
Age (years)
Median	68.0	72.0	71.0	70.0
Range	26-88	36-91	23-89	23-91
Age by category, n (%)
18 to <50	4 (7.4)	4 (8.0)	3 (5.9)	11 (7.1)
50 to <60	6 (11.1)	2 (4.0)	7 (13.7)	15 (9.7)
60 to <70	19 (35.2)	12 (24.0)	13 (25.5)	44 (28.4)
≥70	25 (46.3)	32 (64.0)	28 (54.9)	85 (54.8)
Sex, n (%)
Male	35 (64.8)	30 (60.0)	33 (64.7)	98 (63.2)
Female	19 (35.2)	20 (40.0)	18 (35.3)	57 (36.8)
Race, n (%)
White	54 (100.0)	50 (100.0)	51 (100.0)	155 (100.0)
BMI (kg/m^2)
n	53	50	51	154
Median	27.2	26.6	26.5	26.7
Range	17.4-51.7	17.3-46.5	17.3-40.2	17.3-51.7
Smoking status,^a n (%)
Yes	11 (20.4)	5 (10.0)	14 (27.5)	30 (19.4)
History of diabetes mellitus, n (%)
Yes	25 (46.3)	22 (44.0)	25 (49.0)	72 (46.5)
Duration of hemodialysis (y)
Median	4.2	3.9	3.6	3.8
Range	0.9-17.4	0.5-16.7	0.6-10.2	0.5-17.4
Response to prior hepatitis B vaccination, n (%)
Responded	16 (29.6)	12 (24.0)	10 (19.6)	38 (24.5)
Did not respond	38 (70.4)	38 (76.0)	41 (80.4)	117 (75.5)

BMI, body mass index.

^aSubject smoked within the past year.

Table 2. Seroprotection rate at week 4 (mITT population).

	HepB-CpG		HepB-Eng		HepB-AS04		Difference in SPRs (HepB-CpG – HepB-Eng) (95% CI)^a	Difference in SPRs (HepB-CpG – HepB-AS04) (95% CI)^a	Difference in SPRs (HepB-Eng – HepB-AS04) (95% CI)^a
Visit	Number (n/N) of patients	SPR (95% CI)^a	Number (n/N) of patients	SPR (95% CI)^a	Number (n/N) of patients	SPR (95% CI)^a
Week 4	28/53	52.8% (38.6, 66.7)	15/46	32.6% (19.5, 48.0)	22/51	43.1% (29.3, 57.8)	20.2%^b (0.5, 38.3)	9.7%^c (–9.5, 28.2)	–10.5% (–29.1, 8.9)

anti-HBs, antibody to hepatitis B surface antigen; CI, confidence interval; mITT, modified intent-to-treat population; SPR, seroprotection rate.

^aExact binomial 95% CI (2-sided) for the percentage of patients.

^bStatistically significant difference because lower bound of the 95% CI is >0%.

^cNon-inferiority met because lower bound of the 95% CI is greater than –10%.

Table 3. Anti-HBs geometric mean concentrations at week 4 (mITT population).

Visit	Adjusted GMC (mIU/mL) (95% CI)^a,b			Ratio of GMCs	Ratio of GMCs	Ratio of GMCs
	HepB-CpG (Total N = 53)	HepB-Eng (Total N = 46)	HepB-AS04 (Total N = 51)	HepB-CpG/HepB-Eng (95% CI)	HepB-CpG/HepB-AS04 (95% CI)	HepB-Eng/HepB-AS04 (95% CI)
Day 1	0.32 (0.2, 0.4)	0.31 (0.2, 0.4)	0.33 (0.2, 0.5)	NC	NC	NC
Week 4	9.64 (4.2, 22.1)	2.57 (1.1, 6.0)	4.98 (1.9, 13.0)	3.74^c (1.2, 12.2)	1.94 (0.6, 6.8)	0.52 (0.1, 1.9)

ANOVA, analysis of variance; anti-HBs, antibody to hepatitis B surface antigen; CI, confidence interval; GMC, geometric mean concentration; mITT, modified intent-to-treat population; NC, not calculated.

^aEstimates were obtained through ANOVA with vaccine as the only factor in the model.

^bTo estimate GMCs for each stratum, an ANOVA model with log₁₀ anti-HBs as a dependent variable and vaccine as a factor was used. Adjusted GMC and the corresponding 95% CI were obtained by taking the anti-log of the least squares mean of log₁₀ concentrations and the corresponding 95% CI. Since there is only one factor in the ANOVA model, the adjusted GMCs are identical to the unadjusted GMCs.

^cStatistically significant difference because lower bound of the 95% CI is >1.0.

Table 4. Safety events by vaccination group (safety population).

	HepB-CpG (N = 54)	HepB-Eng (N = 50)	HepB-AS04 (N = 51)
N	54	49	51
Any post-injection reaction ^a	13 (24.1)	8 (16.3)	20 (39.2)
Local reactions
Total, n (%)	5 (9.3)	4 (8.2)	16 (31.4)
Severe	0	0	0
Injection site redness
Total, n (%)	0	0	1 (2.0)
Severe (>100 mm)	0	0	0
Injection site swelling
Total, n (%)	0	0	0
Severe (>100 mm)	0	0	0
Injection site pain
Total, n (%)	5 (9.3)	4 (8.2)	15 (29.4)
Severe	0	0	0
Systemic reactions
Total, n (%)	10 (18.5)	6 (12.2)	10 (19.6)
Severe	1 (1.9)	1 (2.0)	1 (2.0)
Fever (elevated body temperature), N	54	49	51
Total, n (%)	1 (1.9)	2 (4.1)	0 (0.0)
Severe (39°C or higher)	1 (1.9)	1 (2.0)	0 (0.0)
Malaise, N	54	48	51
Total, n (%)	5 (9.3)	2 (4.2)	1 (2.0)
Severe	0	0	0
Headache, N	54	48	51
Total, n (%)	5 (9.3)	1 (2.1)	1 (2.0)
Severe	0	0	0
Myalgia, N	54	49	51
Total, n (%)	4 (7.4)	2 (4.1)	4 (7.8)
Severe	0	0	0
Fatigue, N	54	48	51
Total, n (%)	4 (7.4)	0	5 (9.8)
Severe	0	0	1 (2.0)
Any AE, n (%)	24 (44.4)	22 (44.0)	22 (43.1)
Any related AE, n (%)	2 (3.7)	2 (4.0)	2 (3.9)
Any new-onset autoimmune AE, n (%)	0	0	0
Any SAE, n (%)	10 (18.5)	9 (18.0)	7 (13.7)
Any related SAE, n (%)	0	0	0
Any AE leading to withdrawal, n (%)	0	0	0
Death, n (%)	2 (3.7)	4 (8.0)	0

AE, adverse event; SAE, serious adverse event.

^aPercentages are based on the number of patients (N) providing data for each category. Two patients in each vaccination group did not provide oral temperature data.

Local reactions include redness ≥25 mm, swelling ≥25 mm, and pain. Local pain, malaise, headache, myalgia, and fatigue were graded as severe if they were significant and prevented daily activity.