DENGVAXIA(Dengue Tetravalent Vaccine, Live)Suspension for Subcutaneous Injection(五)
ctions
In Study 1, 1.2% of subjects in the DENGVAXIA group (16/1,333) and 0.8% of subjects in theplacebo group (5/664) reported at least 1 unsolicited non-serious adverse reaction within 28 daysfollowing any dose.
In this study, 0.7% of the subjects in the DENGVAXIA group and 0.5% in the placebo groupreported at least one unsolicited non-serious injection site adverse reaction. The unsolicitednon-serious adverse reactions were injection site pain, hematoma, pruritus and anesthesia in thevaccine group and pain and induration in the control group.
In this study, 0.5% of the subjects in the DENGVAXIA group and 0.3% in the placebo groupreported at least one unsolicited non-serious systemic adverse reaction. The unsolicitednon-serious systemic adverse reactions were malaise, abdominal pain, vomiting, dyspnea,generalized erythema, vertigo, asthma crisis and urticaria in the vaccine group and pruritus andlymphadenitis in the control group.
Most unsolicited non-serious adverse reactions started within 3 days of any injection andresolved within 3 days or less.
A total of 2 subjects (one subject with asthma crisis and urticaria occurring the day of the firstdose, and one subject with malaise occurring 20 days after the first dose) in the DENGVAXIAgroup (0.2%) and none in the placebo group reported unsolicited non-serious Grade 3(significant; prevents daily activity) adverse reactions.
Severe Dengue Following Vaccination with DENGVAXIA and Subsequent Dengue
Infection
Subjects were monitored for severe dengue from Day 0 (day of first study vaccination) to Month60-72 (after first study vaccination) in three multi-center, observer-blind, randomized (2:1),placebo-controlled trials conducted in Latin America and Puerto Rico (Study 1, NCT01374516)and the Asia-Pacific region (Study 2, NCT01373281; Study 3, NCT00842530). A subset of3,203 subjects (80.1%) enrolled in Study 3 were reconsented to participate in an extension studyto eva luate safety of DENGVAXIA for 72 months (Study 4, NCT01983553). A total of 18,265children and adolescents 9 through 16 years of age enrolled in these trials received at least onedose of DENGVAXIA. Table 2 presents the incidences and hazard ratios of severe dengue fromMonth 13 to Month 60-72 post-vaccination with DENGVAXIA or placebo in children and
adolescents 9 through 16 years of age, by dengue baseline serostatus. An increased rate of severedengue was observed following vaccination with DENGVAXIA and subsequent infection withany dengue virus serotype in persons not previously infected by dengue virus. [See Warningsand Precautions (5.1).]
Table 2: Number of Events and Incidence of Severe Dengue* From Month 13 to Month
60-72†
in Children 9 through 16 Years of Age, by Previous Dengue Infection Status, inStudies 1, 2, 3 and 4
Dengue Infection Status at
Month 13‡
DENGVAXIA
n
(Incidence§
, %)
Placebo
n
(Incidence§
, %)
Hazard Ratio of Severe
Dengue
(95% CI)
Previous Dengue Infection
(Dengue sero-positive at Month
13)
10
(0.068)
27
(0.401) 0.18 (0.09; 0.37)
No Previous Dengue Infection
(Dengue sero-negative at Month
13)
12
(0.380)
1
(0.069) 6.25 (0.81; 48.32)
n: number of subject with severe dengue cases
CI: confidence interval
Study 1, NCT01374516; Study 2, NCT01373281; Study 3, NCT00842530; Study 4, NCT01983553
Severe Dengue according to IDMC (Independent Data Monitoring C |
