Vaccine Information: RotaTeq (Page 3 of 4)
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
RotaTeq has not been evaluated for its carcinogenic or mutagenic potential or its potential to impair fertility.
14 CLINICAL STUDIES
Overall, 73,086 infants were randomized in 4 placebo-controlled, phase 3 studies conducted in 12 countries on 4 continents. The data demonstrating the efficacy of RotaTeq in preventing rotavirus gastroenteritis come from 7,744 of these infants from the US (including Navajo and White Mountain Apache Nations), Finland, and Japan who were enrolled in 3 of these studies: Study 006, Study 007, and Study 029. A fourth trial, Study 009, provided clinical evidence supporting the consistency of manufacture and contributed data to the overall safety evaluation.
The racial distribution of the efficacy subset was as follows: White (RotaTeq 61%, placebo 62%); Hispanic-American (RotaTeq 9%, placebo 8%); Black (2% in both groups); Multiracial (4% in both groups); Asian (10% in both groups); Native American (13% in both groups); and Other (<1% in both groups). The gender distribution was 52% male and 48% female in both vaccination groups.
The efficacy evaluations in these studies included: 1) Prevention of any grade of severity of rotavirus gastroenteritis; 2) Prevention of severe rotavirus gastroenteritis, as defined by a clinical scoring system; and 3) Reduction in hospitalizations due to rotavirus gastroenteritis.
The vaccine was given as a three-dose series to healthy infants with the first dose administered between 6 and 12 weeks of age and followed by two additional doses administered at 4- to 10-week intervals. The age of infants receiving the third dose was 32 weeks of age or less. Oral polio vaccine administration was not permitted; however, other childhood vaccines could be concomitantly administered. Breast-feeding was permitted in all studies.
The case definition for rotavirus gastroenteritis used to determine vaccine efficacy required that a subject meet both of the following clinical and laboratory criteria: (1) greater than or equal to 3 watery or looser-than-normal stools within a 24-hour period and/or forceful vomiting; and (2) rotavirus antigen detection by enzyme immunoassay (EIA) in a stool specimen taken within 14 days of onset of symptoms. The severity of rotavirus acute gastroenteritis was determined by a clinical scoring system that took into account the intensity and duration of symptoms of fever, vomiting, diarrhea, and behavioral changes.
The primary efficacy analyses included cases of rotavirus gastroenteritis caused by types G1, G2, G3, G4 (and G types containing P1A8 (in Study 029 only)) that occurred at least 14 days after the third dose through the first rotavirus season post vaccination.
Analyses were also done to evaluate the efficacy of RotaTeq against rotavirus gastroenteritis caused by any of types G1, G2, G3, and G4 (and G types containing P1A8 (in Study 029 only)) at any time following the first dose through the first rotavirus season postvaccination among infants who received at least one vaccination (Intent-to-treat, ITT).
14.1 Rotavirus Efficacy and Safety Trial (Study 006)
Primary efficacy against any grade of severity of rotavirus gastroenteritis caused by naturally occurring types G1, G2, G3, or G4 through the first rotavirus season after vaccination was 74.0% (95% CI: 66.8, 79.9) and the ITT efficacy was 60.0% (95% CI: 51.5, 67.1). Primary efficacy against severe rotavirus gastroenteritis caused by naturally occurring types G1, G2, G3, or G4 through the first rotavirus season after vaccination was 98.0% (95% CI: 88.3, 100.0), and ITT efficacy was 96.4% (95% CI: 86.2, 99.6). See Table 8.
Per Protocol | Intent-to-Treat † | |||
RotaTeq | Placebo | RotaTeq | Placebo | |
Subjects vaccinated | 2,834 | 2,839 | 2,834 | 2,839 |
Gastroenteritis cases | ||||
Any grade of severity | 82 | 315 | 150 | 371 |
Severe * | 1 | 51 | 2 | 55 |
Efficacy estimate % and (95% confidence interval) | ||||
Any grade of severity | 74.0(66.8, 79.9) | 60.0(51.5, 67.1) | ||
Severe * | 98.0(88.3, 100.0) | 96.4(86.2, 99.6) |
The efficacy of RotaTeq against severe disease was also demonstrated by a reduction in hospitalizations for rotavirus gastroenteritis among all subjects enrolled in Study 006. RotaTeq reduced hospitalizations for rotavirus gastroenteritis caused by types G1, G2, G3, and G4 through the first two years after the third dose by 95.8% (95% CI: 90.5, 98.2). The ITT efficacy in reducing hospitalizations was 94.7% (95% CI: 89.3, 97.3) as shown in Table 9.
| ||||
Per Protocol | Intent-to-Treat * | |||
RotaTeq | Placebo | RotaTeq | Placebo | |
Subjects vaccinated | 34,035 | 34,003 | 34,035 | 34,003 |
Number of hospitalizations | 6 | 144 | 10 | 187 |
Efficacy estimate % and(95% confidence interval) | 95.8(90.5, 98.2) | 94.7(89.3, 97.3) |
14.2 Study 007
Primary efficacy against any grade of severity of rotavirus gastroenteritis caused by naturally occurring types G1, G2, G3, or G4 through the first rotavirus season after vaccination was 72.5% (95% CI: 50.6, 85.6) and the ITT efficacy was 58.4% (95% CI: 33.8, 74.5). Primary efficacy against severe rotavirus gastroenteritis caused by naturally occurring types G1, G2, G3, or G4 through the first rotavirus season after vaccination was 100% (95% CI: 13.0, 100.0) and ITT efficacy against severe rotavirus disease was 100% (95% CI: 30.2, 100.0) as shown in Table 10.
Per Protocol | Intent-to-Treat † | |||
RotaTeq | Placebo | RotaTeq | Placebo | |
Subjects vaccinated | 650 | 660 | 650 | 660 |
Gastroenteritis cases | ||||
Any grade of severity | 15 | 54 | 27 | 64 |
Severe * | 0 | 6 | 0 | 7 |
Efficacy estimate % and (95% confidence interval) | ||||
Any grade of severity | 72.5(50.6, 85.6) | 58.4(33.8, 74.5) | ||
Severe * | 100.0(13.0, 100.0) | 100.0(30.2, 100.0) |
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