General Information

RotaTeq is a live, orally administered pentavalent vaccine containing five reassorted rotaviruses. The vaccine is designed to target the viral serotypes that are most common and most frequently associated with severe gastroenteritis.

RotaTeq is specifically indicated for the prevention of rotavirus gastroenteritis in infants and children caused by the rotavirus serotypes G1, G2, G3 and G4 in infants between the ages of 6 to 32 weeks.

Mechanism of Action

RotaTeq is designed to elicit immune response against a broad spectrum of rotavirus strains. The vaccine is composed of five strains of live reassorted rotavirus. Four of the strains express one of the capsid proteins (G1, G2, G3, G4) from the human rotavirus parent and the attachment protein P7[5] from bovine rotavirus. The fifth strain expresses the P1[8] attachment protein from the human rotavirus strain and the G6 bovine rotavirus capsid protein.

Side Effects

Adverse events associated with the use of RotaTeq may include, but are not limited to, the following:

• diarrhea
• irritability
• otitis media
• vomiting
• nasopharyngitis
• bronchospasm

Dosing/Administration

RotaTeq is supplied as a pale yellow, clear suspension for oral delivery. A standard regimen is administered as three 2 ml oral doses: the first should be administered at 6-12 weeks of age, with subsequent doses administered on four- to 10-week intervals (the last dose should be administered before the infant reaches 32 weeks of age).

Clinical Trial Results

Approval of RotaTeq was based on results of three phase 3 trials of the drug, which treated a combined 72,324 infants in 11 countries. Two of the studies, the Rotavirus Efficacy and Safety Trial (REST) and Study 007, were designed to investigate the efficacy of the drug; the third, Study 009, was designed to investigate the vaccine's safety and manufacturing consistency.

REST Study
This placebo-controlled study investigated the primary efficacy of the vaccine (n=2834), compared to placebo (n=2839). In the primary efficacy analysis (including subjects finishing the vaccination course), all-severity gastroenteritis occurred in 82 subjects in the vaccine group, compared to 315 in the placebo group (74.0 percent efficacy); severe rotavirus gastroenteritis occurred in 1 vaccine subject, and 51 placebo subjects (98.0 percent efficacy). Intent to treat (ITT) analysis (including subjects receiving at least one dose of the vaccine) efficacy rates in all-severity and serious enteritis were 60 percent (n=150 vs. 371) and 96.4 percent, (n=2 vs. 55) respectively. Secondary efficacy measures were also positive, with the vaccine significantly reducing hospitalizations for gastroenteritis due to G1, G2, G3 and G4 rotavirus infection in both full-regimen (95.8 percent reduction; n=6 vs. 144) and ITT (94.7 percent; n=10 vs. 187) populations.

Study 007
This placebo-controlled study investigated the efficacy of the drug in reducing gastroenteritis due to rotavirus serotypes G1, G2, G3 or G4 during the first viral season. Efficacy in reducing all-severity disease was 72.5 percent in the primary efficacy group, and 58.4 percent in the trial's ITT group. Efficacy in reducing incidence of severe disease for both primary and ITT populations was 100 percent.

Ongoing Study Commitments

• A large-scale observational, post-licensure safety study to evaluate the incidence of intussusception and other safety parameters in recipients of RotaTeq in approximately 44,000 subjects (adjustments to the sample size will be made based on the background rate of intussusception). The study will be designed to detect an increased risk of intussusception due to vaccine of 2.5 or greater with 80 percent probability.
  Protocol Submission: May 2006
  Study Start: Q3 2006
  Final Report Submission: Q4 2008
• An adequately powered non-inferiority study of the concomitant administration of RotaTeq with acellular pertussis vaccine in which serological endpoints will be examined using a validated assay. The study will be powered sufficiently to detect a 1.5-fold difference in GMTs.
  First Protocol Submission: May 2006