luated for its carcinogenic or mutagenic potential. Vaccination of female rats with SHINGRIX had no effect on fertility [see Use in Specific Populations (8.1)]. In a male fertility study, rats were vaccinated with 0.1 mL of SHINGRIX (a single human dose is 0.5 mL) on 42, 28, and 14 days prior to mating. There were no effects on male fertility.
14 CLINICAL STUDIES
14.1 Efficacy in Subjects 50 Years and Older
Study 1 was a randomized, placebo-controlled, observer-blind clinical study conducted in 18 countries. Randomization was stratified (8:5:3:1) by age: 50 to 59 years, 60 to 69 years, 70 to 79 years, and ≥80 years. The study excluded, among others, subjects who were immunocompromised, had a history of previous HZ, were vaccinated against varicella or HZ, and patients whose survival was not expected to be at least 4 years or with conditions that might interfere with study eva luations. Subjects were followed for the development of HZ and postherpetic neuralgia (PHN) for a median of 3.1 years (range: 0 to 3.7 years). Suspected HZ cases were followed prospectively for the development of PHN, an HZ-related complication defined as HZ-associated pain (rated as 3 or greater on a 0- to 10-point scale by the study subject) occurring or persisting at least 90 days following the onset of rash in confirmed cases of HZ.
The primary efficacy analysis population (referred to as the modified Total Vaccinated Cohort [mTVC]) included 14,759 subjects aged 50 years and older who received 2 doses (0 and 2 months) of either SHINGRIX (n = 7,344) or placebo (n = 7,415) and did not develop a confirmed case of HZ within 1 month after the second dose. In the mTVC population, 61.2% were female; 72.3% were white, 18.9% were Asian, 1.7% were black, and 7.0% were of other racial/ethnic groups. The mean age of subjects was 62.3 years.
Confirmed HZ cases were determined by either Polymerase Chain Reaction (PCR) (89.4%) or by a Clinical eva luation Committee (10.6%).
Efficacy against Herpes Zoster
Compared with placebo, SHINGRIX significantly reduced the risk of developing HZ by 97.2% (95% CI: 93.7, 99.0) in subjects 50 years and older (Table 2).
Table 2. Efficacy of SHINGRIX on Incidence of Herpes Zoster Compared with Placebo in Study 1a (mTVCb)
Age Group
(Years)
SHINGRIX
Placebo
% Efficacy (95% CI)
N
n
Incidence Rate of HZ per 1,000 Person-Years
N
n
Incidence Rate of HZ per 1,000 Person-Years
Overall (≥50)c
7,344
6
0.3
7,415
210
9.1
97.2
(93.7, 99.0)
50 - 59
3,492
3
0.3
3,525
87
7.8
96.6
(89.6, 99.3)
60 - 69
2,141
2
0.3
2,166
75
10.8
97.4
(90.1, 99.7)
≥70
1,711
1
0.2
1,724
48
9.4
97.9
(87.9, 100.0)
N = Number of subjects included in each group; n = Number of subjects having at least 1 confirmed HZ episode; HZ = Herpes zoster; CI = Confidence Interval.
a Study 1: NCT01165177.
b mTVC = Modified Total Vaccinated Cohort defined as subjects who received 2 doses (0 and 2 months) of either SHINGRIX or placebo and did not develop a confirmed case of HZ within 1 month after the second dose.
c Primary study endpoint was based on confirmed HZ cases in subjects aged 50 years and older.
In a descriptive analysis, vaccine efficacy against HZ in subjects aged 50 years and older was 93.1% (95% CI: 81.3, 98.2) in the fourth year post-vaccination.
Occurrence of PHN
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