Rotavirus Infections, Gastroenteritis
Conditions
Brief summary
The study is being conducted to demonstrate that vaccine to prevent gastroenteritis due to rotavirus may be administered concomitantly with oral polio vaccine (OPV) without impairing the safety or immunogenicity of either vaccine.
Interventions
Three doses of rotavirus vaccine, live, oral, pentavalent. Dose 1 was given on Day 1, Dose 2 was given 56 to 84 days post Dose 1, and Dose 3 was given 56 to 84 days post Dose 2.
BIOLOGICALComparator: Oral Poliovirus Vaccine (OPV)
Three doses OPV. Dose 1 was given on Day 1, Dose 2 was given 56 to 84 days post Dose 1, and Dose 3 was given 56 to 84 days post Dose 2.
BIOLOGICALComparator: Oral Poliovirus Vaccine (OPV) (staggered)
Three doses OPV. Dose 1 was given 14 to 28 days post Dose 1 of RotaTeq, Dose 2 was given 14 to 28 days post Dose 2 of RotaTeq, and Dose 3 was given 14 to 28 days post Dose 3 of RotaTeq.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Infants in good health
Exclusion criteria
* Previous administration of any oral poliovirus vaccine (OPV) and rotavirus vaccine * Receipt of inactivated poliovirus vaccine (IPV) prior to the first dose of either study vaccine, or at any time during the course of the study * Any condition resulting in depressed immunity * Any allergy to any vaccine component as stated in the package circulars * Allergies to polymyxin B, neomycin or any other antibiotics * Receipt of intramuscular, oral, or intravenous corticosteroid treatment * History of congenital abdominal disorders, intussusception, or abdominal surgery; clinical evidence of active gastrointestinal illness * History of known prior rotavirus gastroenteritis, chronic diarrhea, or failure to thrive * Prior receipt of a blood transfusion or blood products, including immunoglobulin * Fever, with a rectal temperature of ≥38.1°C (≥ 100.5°F) at the time of immunization * Infants residing in a household with an immunocompromised person
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Approximately 42 days Postdose 3 | GMT of poliovirus type 1, 2, and 3, measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered. |
| GMT of Serum Anti-rotavirus Immunoglobulin A (IgA) | Approximately 42 days Postdose 3 | GMT of serum anti-rotavirus IgA measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered |
| Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | Approximately 42 days Postdose 3 | Rotavirus SNA response to serotypes G1, G2, G3, G4, and P1A measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered. |
Participant flow
Recruitment details
Enrollment occurred at 9 study sites in Mexico, Costa Rica, Guatemala, and Brazil from 19-Oct-2005 (first subject in) to 06-Jan-2006 (last subject randomized).
Pre-assignment details
Excluded from randomization were subjects with history of congenital abdominal disorders, intussusception, or abdominal surgery; history of known prior rotavirus disease, chronic diarrhea, or failure to thrive, clinical evidence of active gastrointestinal illness and those with fever, a rectal temperature ≥38.1°C (≥100.5°F) at time of immunization.
Participants by arm
| Arm | Count |
|---|---|
| RotaTeq and Oral Poliovirus (OPV) Concomitantly Subjects (Sbjs) in Group 1 who received 3 concomitant doses of RotaTeq™ and OPV ≥56 to ≤84 days (8 to 10 weeks) apart | 372 |
| RotaTeq and Oral Poliovirus (OPV) Staggered Subjects in Group 2, who received RotaTeq™ first followed by OPV between ≥14 to ≤28 days (2 to 4 weeks) later | 363 |
| Total | 735 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Moved | 2 | 2 |
| Overall Study | Other | 0 | 3 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Withdrawal by Subject | 6 | 1 |
Baseline characteristics
| Characteristic | RotaTeq and Oral Poliovirus (OPV) Concomitantly | RotaTeq and Oral Poliovirus (OPV) Staggered | Total |
|---|---|---|---|
| Age, Customized 5 Weeks of Age and Under | 8 participants | 1 participants | 9 participants |
| Age, Customized 6 to 12 Weeks of Age | 364 participants | 362 participants | 726 participants |
| Age, Customized Over 12 Weeks of Age | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Black | 10 participants | 7 participants | 17 participants |
| Race/Ethnicity, Customized Hispanic American | 263 participants | 257 participants | 520 participants |
| Race/Ethnicity, Customized Multi-Racial | 56 participants | 61 participants | 117 participants |
| Race/Ethnicity, Customized White | 41 participants | 37 participants | 78 participants |
| Sex: Female, Male Female | 189 Participants | 194 Participants | 383 Participants |
| Sex: Female, Male Male | 183 Participants | 169 Participants | 352 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 342 / 366 | 325 / 359 |
| serious Total, serious adverse events | 4 / 366 | 9 / 359 |
Outcome results
Primary
Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3
GMT of poliovirus type 1, 2, and 3, measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered.
Time frame: Approximately 42 days Postdose 3
Population: The primary immunogenicity analyses were based on evaluable per-protocol subjects who received all scheduled doses, were not protocol violators, and had valid assay values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 1 | 888.0 Geometric Mean Titer (GMT) |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 2 | 814.9 Geometric Mean Titer (GMT) |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 3 | 233.6 Geometric Mean Titer (GMT) |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 1 | 1139 Geometric Mean Titer (GMT) |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 2 | 814.5 Geometric Mean Titer (GMT) |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Geometric Mean Titer(s) of Poliovirus Types 1, 2, and 3, Measured Approximately 42 Days Postdose 3 | Antibody Responses to Poliovirus Type 3 | 269.2 Geometric Mean Titer (GMT) |
Comparison: Seroprotection rate (proportion of subjects who achieve the seroprotection criteria: neutralizing antibody titers \[NA\] ≥1:8) for poliovirus type 1p-value: <0.00195% CI: [-2.2, 1.4]Miettinen and Nurminen's
Comparison: Seroprotection rate (proportion of subjects who achieve the seroprotection criteria: neutralizing antibody titers \[NA\] ≥1:8) for poliovirus type 2p-value: <0.00195% CI: [-1.4, 1.6]Miettinen and Nurminen's
Comparison: Seroprotection rate (proportion of subjects who achieve the seroprotection criteria: neutralizing antibody titers \[NA\] ≥1:8) for poliovirus type 3p-value: <0.00195% CI: [-2.3, 2.3]Miettinen and Nurminen's
Primary
GMT of Serum Anti-rotavirus Immunoglobulin A (IgA)
GMT of serum anti-rotavirus IgA measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered
Time frame: Approximately 42 days Postdose 3
Population: Per Protocol Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | GMT of Serum Anti-rotavirus Immunoglobulin A (IgA) | 154.9 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | GMT of Serum Anti-rotavirus Immunoglobulin A (IgA) | 292.7 GMT |
p-value: 0.27795% CI: [0.42, 0.69]ANOVA
p-value: 0.00295% CI: [-8, -1.4]Miettinen and Nurminen's
Primary
Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered
Rotavirus SNA response to serotypes G1, G2, G3, G4, and P1A measured at postdose 3 in subjects receiving RotaTeq™ and OPV concomitantly compared to staggered.
Time frame: Approximately 42 days Postdose 3
Population: Per Protocol Population~For serotype G4 the RotaTeq and Oral Poliovirus (OPV) concomitantly group N = 350
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G2 | 27.1 GMT |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G4 | 58.5 GMT |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G3 | 21.2 GMT |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes P1A | 84.7 GMT |
| RotaTeq and Oral Poliovirus (OPV) Concomitantly | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G1 | 125.8 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes P1A | 131.4 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G1 | 182.6 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G2 | 30.0 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G3 | 22.5 GMT |
| RotaTeq and Oral Poliovirus (OPV) Staggered | Immunogenicity of RotaTeq™ as Measured by Serum Neutralizing Antibody [SNA] Responses to Rotavirus Serotypes G1, G2, G3, G4, and P1A When Administered With OPV Concomitantly or Staggered | SNA responses to rotavirus serotypes G4 | 74.5 GMT |