Diarrhea, Fever, Vomiting
Conditions
Brief summary
The purpose of the current study is to evaluate whether the vaccine is effective, well-tolerated and immunogenic among infants in developing countries.
Interventions
BIOLOGICALRotaTeq™ - Rotavirus Vaccine, Live, Oral, Pentavalent
2.0 mL oral dose of RotaTeq™. 14 week treatment period
BIOLOGICALComparator: Placebo
Arm 2: Placebo. 14 week treatment period
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Age 4 weeks through 12 weeks at Dose 1 * Parent able to understand study procedures and give consent
Exclusion criteria
* Clinical evidence of active gastrointestinal disease * Subjects who are currently or expected to participate in other studies of investigational products during the 6 weeks after receiving the last dose of RotaTeq™/placebo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | At least 14 days following the third vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | 14 days following the 3rd vaccination | Induction of postdose 3 SNA response (Number of subjects with ≥ 3 fold rise in antibody titer) |
| Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | 14 days following the 3rd vaccination | Induction of postdose 3 SNA response (Number of subjects with ≥ 3 fold rise in antibody titer) |
Participant flow
Recruitment details
The study was conducted at 5 international sites - Ghana, Kenya, Mali, Bangladesh, and Vietnam from 29 March 2007 (first patient in) to 13 October 2008 (last dose given). Last subject completed follow-up: 31 March 2009 All data corrections applied (Frozen File): 20 July 2009
Pre-assignment details
Excluded from the trial before assignment to groups were subjects: with history of active gastrointestinal illness (vomiting, diarrhea, elevated temperature); who were participating in (or expected to participate in) other investigational-product studies; who could not be followed adequately for safety.
Participants by arm
| Arm | Count |
|---|---|
| RotaTeq™ - Africa Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study. | 2,733 |
| Placebo - Africa Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study. | 2,735 |
| RotaTeq™ - Asia Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study. | 1,018 |
| Placebo - Asia Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study. | 1,018 |
| Total | 7,504 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 21 | 1 | 0 |
| Overall Study | Lost to Follow-up | 62 | 69 | 4 | 3 |
| Overall Study | Protocol Violation | 4 | 2 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 48 | 42 | 2 | 6 |
Baseline characteristics
| Characteristic | RotaTeq™ - Africa | Placebo - Africa | RotaTeq™ - Asia | Placebo - Asia | Total |
|---|---|---|---|---|---|
| Age, Customized <27 Days | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Age, Customized 27 to 41 Days | 536 participants | 569 participants | 3 participants | 7 participants | 1115 participants |
| Age, Customized 42 to 84 Days | 2197 participants | 2165 participants | 1015 participants | 1011 participants | 6388 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 1017 participants | 1016 participants | 2033 participants |
| Race/Ethnicity, Customized Black | 2733 participants | 2735 participants | 0 participants | 0 participants | 5468 participants |
| Race/Ethnicity, Customized Multi-Racial | 0 participants | 0 participants | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 1359 Participants | 1370 Participants | 464 Participants | 492 Participants | 3685 Participants |
| Sex: Female, Male Male | 1374 Participants | 1365 Participants | 554 Participants | 526 Participants | 3819 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 137 / 149 | 147 / 152 |
| serious Total, serious adverse events | 144 / 3,744 | 156 / 3,745 | 1 / 3 | 0 / 1 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose
Time frame: At least 14 days following the third vaccination
Population: Per Protocol Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RotaTeq™ - Africa | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects with rotavirus gastroenteritis cases | 79 Subjects |
| RotaTeq™ - Africa | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects without rotavirus gastroenteritis cases | 2278 Subjects |
| Placebo - Africa | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects without rotavirus gastroenteritis cases | 2219 Subjects |
| Placebo - Africa | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects with rotavirus gastroenteritis cases | 129 Subjects |
| RotaTeq™ - Asia | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects with rotavirus gastroenteritis cases | 38 Subjects |
| RotaTeq™ - Asia | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects without rotavirus gastroenteritis cases | 953 Subjects |
| Placebo - Asia | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects with rotavirus gastroenteritis cases | 71 Subjects |
| Placebo - Asia | Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose | Subjects without rotavirus gastroenteritis cases | 907 Subjects |
Comparison: The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.p-value: <0.00195% CI: [19.1, 54.7]Exact binomial test
Comparison: The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.p-value: <0.00195% CI: [22.3, 66.1]Exact binomial test
Secondary
Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]
Induction of postdose 3 SNA response (Number of subjects with ≥ 3 fold rise in antibody titer)
Time frame: 14 days following the 3rd vaccination
Population: Per Protocol Population~\*N analyzed for Serotype P1A\[8\] is 188
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in anti-rotavirus IgA | 148 Subjects |
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G1 | 35 Subjects |
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G2 | 17 Subjects |
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G3 | 12 Subjects |
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G4 | 50 Subjects |
| RotaTeq™ - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype P1A[8] | 27 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G4 | 4 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in anti-rotavirus IgA | 34 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G3 | 4 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G1 | 0 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype P1A[8] | 8 Subjects |
| Placebo - Africa | Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G2 | 5 Subjects |
Comparison: Anti-rotavirus IgA95% CI: [71.7, 84]
Comparison: Serotype G195% CI: [13.3, 24.8]
Comparison: Serotype G295% CI: [5.3, 14]
Comparison: Serotype G395% CI: [3.3, 10.8]
Comparison: Serotype G495% CI: [20.3, 33.3]
Comparison: Serotype P1A\[8\]95% CI: [9.7, 20.2]
Comparison: Anti-rotavirus IgA95% CI: [14.4, 27]
Comparison: Serotype G195% CI: [0, 2.2]
Comparison: Serotype G295% CI: [1, 6.8]
Comparison: Serotype G395% CI: [0.6, 5.9]
Comparison: Serotype G495% CI: [0.6, 5.9]
Comparison: Serotype P1A\[8\]95% CI: [2.1, 9.1]
Secondary
Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]
Induction of postdose 3 SNA response (Number of subjects with ≥ 3 fold rise in antibody titer)
Time frame: 14 days following the 3rd vaccination
Population: Per Protocol Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G1 | 42 Subjects |
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G4 | 24 Subjects |
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G2 | 13 Subjects |
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype P1A[8] | 36 Subjects |
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G3 | 37 Subjects |
| RotaTeq™ - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in anti-rotavirus IgA | 115 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G2 | 1 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in anti-rotavirus IgA | 24 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G1 | 3 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G3 | 4 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype G4 | 0 Subjects |
| Placebo - Africa | Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | ≥ 3 fold rise in antibody titer: Serotype P1A[8] | 7 Subjects |
Comparison: Anti-rotavirus IgA95% CI: [80.9, 92.9]
Comparison: Serotype G195% CI: [24.2, 40.8]
Comparison: Serotype G295% CI: [5.4, 16.4]
Comparison: Serotype G395% CI: [20.7, 36.8]
Comparison: Serotype G495% CI: [12.1, 26]
Comparison: Serotype P1A\[8\]95% CI: [20, 36]
Comparison: Anti-rotavirus IgA95% CI: [12, 25.8]
Comparison: Serotype G195% CI: [0.5, 6.5]
Comparison: Serotype G295% CI: [0, 4.1]
Comparison: Serotype G395% CI: [0.8, 7.6]
Comparison: Serotype G495% CI: [0, 2.8]
Comparison: Serotype P1A\[8\]95% CI: [2.2, 10.6]