Rotavirus Infections
Conditions
Brief summary
This study was designed to evaluate the safety of the investigational Rotavirus Vaccine and the efficacy to prevent Rotavirus Gastroenteritis.
Detailed description
The duration of treatment is 10 months.
Interventions
BIOLOGICALRotaTeq™, rotavirus vaccine, live, oral, pentavalent
Three doses of RotaTeq™ administered 28 to 70 days apart.
BIOLOGICALComparator: Placebo matching RotaTeq™
Placebo matching RotaTeq™ administered 28 to 70 days apart.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Healthy infants
Exclusion criteria
* History of abdominal disorders from a birth defect, intussusception, or abdominal surgery * Known or suspected problems with immune system * Fever at time of immunization * Prior administration of a rotavirus vaccine * History of known prior rotavirus disease * Chronic diarrhea, or failure to thrive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of Clinical Rotavirus Disease Caused by the Composite of the Serotypes Contained Within the Vaccine More Than 14 Days Following the Third Dose. | At least 14 days following the 3rd vaccination | G1, G2, G3, and G4 Serotype Rotavirus Gastroenteritis Cases Occurring at Least 14 Days Postdose 3 Through the First Rotavirus Season Postvaccination in the Per-Protocol Population Using Per-Protocol Case Definition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With ≥3 Fold Rise in Antibody Titer | 14 days following the 3rd vaccination | Induction of postdose 3 rotavirus Serum neutralizing antibody (SNA) response (Number of subjects with ≥3 fold rise in antibody titer) |
Participant flow
Recruitment details
The study was conducted at 30 sites - 27 in the United States, and 3 in Finland from 24-Sep-2002 (first patient in) to 11-Feb-2004 (last dose given). Last subject completed follow-up: 08-Jun-2004. All data corrections applied (Frozen File): 07-Sep-2004
Pre-assignment details
Excluded from the trial before assignment to groups were patients with: history of congenital abdominal disorders, intussusception, or abdominal surgery; history of known prior rotavirus disease, chronic diarrhea, or failure to thrive.
Participants by arm
| Arm | Count |
|---|---|
| RotaTeq™ at Expiry Potency (≈1.1 x 10^7 IU/Dose) Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 42 days of safety follow-up after each vaccination, and followup for acute gastrointestinal episodes (AGEs) through the first rotavirus season post vaccination. | 651 |
| Placebo Matching RotaTeq™ Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 42 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season post vaccination. | 661 |
| Total | 1,312 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 13 |
| Overall Study | Lost to Follow-up | 7 | 3 |
| Overall Study | Moved | 5 | 5 |
| Overall Study | Other | 17 | 13 |
| Overall Study | Protocol Violation | 11 | 9 |
| Overall Study | Withdrawal by Subject | 9 | 11 |
Baseline characteristics
| Characteristic | RotaTeq™ at Expiry Potency (≈1.1 x 10^7 IU/Dose) | Placebo Matching RotaTeq™ | Total |
|---|---|---|---|
| Age, Customized 6 to 12 Weeks | 648 participants | 658 participants | 1306 participants |
| Age, Customized Over 12 Weeks | 3 participants | 3 participants | 6 participants |
| Race/Ethnicity Black | 21 participants | 23 participants | 44 participants |
| Race/Ethnicity Hispanic American | 79 participants | 77 participants | 156 participants |
| Race/Ethnicity Multi-Racial | 17 participants | 15 participants | 32 participants |
| Race/Ethnicity Other | 9 participants | 6 participants | 15 participants |
| Race/Ethnicity White | 525 participants | 540 participants | 1065 participants |
| Sex: Female, Male Female | 304 Participants | 323 Participants | 627 Participants |
| Sex: Female, Male Male | 347 Participants | 338 Participants | 685 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 558 / 649 | 565 / 658 |
| serious Total, serious adverse events | 21 / 649 | 28 / 658 |
Outcome results
Primary
Occurence of Clinical Rotavirus Disease Caused by the Composite of the Serotypes Contained Within the Vaccine More Than 14 Days Following the Third Dose.
G1, G2, G3, and G4 Serotype Rotavirus Gastroenteritis Cases Occurring at Least 14 Days Postdose 3 Through the First Rotavirus Season Postvaccination in the Per-Protocol Population Using Per-Protocol Case Definition
Time frame: At least 14 days following the 3rd vaccination
Population: Per Protocol Population; number randomized is different from number analyzed due to some data excluded from the analysis (e.g., unevaluable due to wild-type rotavirus-positive stool antigen Enzyme immunoassay (EIA) prior to 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RotaTeq™ at Expiry Potency (≈1.1 x 107 IU/Dose) | Occurence of Clinical Rotavirus Disease Caused by the Composite of the Serotypes Contained Within the Vaccine More Than 14 Days Following the Third Dose. | 15 Participants |
| Placebo Matching RotaTeq™ | Occurence of Clinical Rotavirus Disease Caused by the Composite of the Serotypes Contained Within the Vaccine More Than 14 Days Following the Third Dose. | 54 Participants |
p-value: <0.00195% CI: [50.6, 85.6]Exact Binomial Test
Secondary
Number of Subjects With ≥3 Fold Rise in Antibody Titer
Induction of postdose 3 rotavirus Serum neutralizing antibody (SNA) response (Number of subjects with ≥3 fold rise in antibody titer)
Time frame: 14 days following the 3rd vaccination
Population: Per Protocol Population; number randomized is different from number analyzed due to some data excluded from the analysis (e.g., unevaluable due to wild-type rotavirus-positive stool antigen EIA prior to 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RotaTeq™ at Expiry Potency (≈1.1 x 107 IU/Dose) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 38 Participants |
| Placebo Matching RotaTeq™ | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 9 Participants |
| RotaTeq™ at Expiry Potency (SNA - G3) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 6 Participants |
| RotaTeq™ at Expiry Potency (SNA - G4) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 25 Participants |
| RotaTeq™ at Expiry Potency (SNA - P1A) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 15 Participants |
| Placebo Matching RotaTeq™ (SNA - G1) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 2 Participants |
| Placebo Matching RotaTeq™ (SNA - G2) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 0 Participants |
| Placebo Matching RotaTeq™ (SNA - G3) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 0 Participants |
| Placebo Matching RotaTeq™ (SNA - G4) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 1 Participants |
| Placebo Matching RotaTeq™ (SNA - P1A) | Number of Subjects With ≥3 Fold Rise in Antibody Titer | 2 Participants |
95% CI: [44, 66.8]
95% CI: [0.3, 9.5]
95% CI: [6.9, 25.8]
95% CI: [0, 5.1]
95% CI: [3.4, 18.5]
95% CI: [0, 4.8]
95% CI: [27.6, 52.8]
95% CI: [0, 7.7]
95% CI: [14.5, 37.3]
95% CI: [0.4, 10.1]