Rotavirus Gastroenteritis
Conditions
Brief summary
A study to compare safety, tolerability, and immunogenicity of a new formulation of RotaTeq™ with the existing formulation in infants. The primary hypothesis of the study is that the new formulation will be noninferior to the existing formulation on the basis of immunogenicity.
Interventions
BIOLOGICALRotaTeq™ experimental formulation
BIOLOGICALRotaTeq™ existing formulation
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 12 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Parent or legal guardian agrees to have infant participate by giving written informed consent
Exclusion criteria
* History of congenital abdominal disorders, prior rotavirus gastroenteritis, chronic diarrhea, failure to thrive, or abdominal surgery * History of intussusception * Known or suspected impairment of immunological function, including Severe Combined Immunodeficiency (SCID) * Prior administration of any rotavirus vaccine * Clinical evidence of active gastrointestinal illness, with the exception of well-controlled gastroesophageal reflux disease (GERD) * Receipt of 1) systemic corticosteroids (≥ 2mg/kg total daily dose of prednisone or equivalent) for 14 consecutive days or more since birth, or 2) systemic corticosteroids ≥ 2mg/kg/dose within 7 days prior to the administration of the first dose of study vaccine. Participant using non-systemic corticosteroids will be eligible for vaccination. * Residing in a household with an immunocompromised person * Prior receipt of a blood transfusion or blood products, including immunoglobulins * Participation in another interventional study within 14 days prior to the first study vaccination or expected anytime during the study * Receipt of investigational inactivated vaccines within 14 days or investigational live vaccines within 28 days prior to the first study vaccination or expected anytime during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | 42 days after vaccination 3 (up to 185 days) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Up to 7 days after any vaccination (up to 147 days) | An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. Protocol-defined Tier-1 adverse events to be collected up to 7 days after any vaccination were diarrhea, vomiting, elevated temperature (rectal \>=38.1° C, \>=100.5° F), and irritability. |
| Number of Participants With Tier-1 Adverse Events: Intussusception | Up to Day 185 | The protocol-defined Tier-1 adverse event to be collected for the duration of the study (up to Day 185) was intussusception |
| Geometric Mean Titer of Serum Anti-Rotavirus Immunoglobulin A | 42 days after vaccination 3 (up to 185 days) | — |
| Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Baseline and 42 days after vaccination 3 (up to 185 days) | — |
Participant flow
Pre-assignment details
A total of 1039 participants were screened
Participants by arm
| Arm | Count |
|---|---|
| RotaTeq™ Experimental Formulation Three 2.0 mL oral doses of RotaTeq™ experimental formulation. Vaccination 1 will be administered between 6 and 12 weeks of age and the third vaccination will be administered before 32 weeks of age. Each vaccination will be separated from the next by ≥ 4 weeks (28 days). | 513 |
| RotaTeq™ Existing Formulation Three 2.0 mL oral doses of RotaTeq™ existing formulation. Vaccination 1 will be administered between 6 and 12 weeks of age and the third vaccination will be administered before 32 weeks of age. Each vaccination will be separated from the next by ≥ 4 weeks (28 days). | 507 |
| Total | 1,020 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Randomized but not vaccinated | 3 | 3 |
| Overall Study | Withdrawal by parent/guardian | 8 | 6 |
Baseline characteristics
| Characteristic | RotaTeq™ Experimental Formulation | RotaTeq™ Existing Formulation | Total |
|---|---|---|---|
| Age, Continuous | 8.4 Weeks STANDARD_DEVIATION 1.4 | 8.3 Weeks STANDARD_DEVIATION 1.4 | 8.3 Weeks STANDARD_DEVIATION 1.4 |
| Sex: Female, Male Female | 232 Participants | 240 Participants | 472 Participants |
| Sex: Female, Male Male | 281 Participants | 267 Participants | 548 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 398 / 508 | 385 / 499 |
| serious Total, serious adverse events | 20 / 508 | 12 / 499 |
Outcome results
Primary
Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]
Time frame: 42 days after vaccination 3 (up to 185 days)
Population: Participants who received the 3 scheduled doses of study vaccine, did not have important protocol deviations, and had follow-up results for the endpoint
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G1 | 99.8 Titer |
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G4 | 78.9 Titer |
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G2 | 30.0 Titer |
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype P1A[8] | 106.9 Titer |
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G3 | 82.8 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype P1A[8] | 90.1 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G1 | 106.1 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G3 | 25.2 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G4 | 71.5 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Neutralizing Antibody Response to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G2 | 26.3 Titer |
Comparison: Serotype G195% CI: [0.79, 1.07]
Comparison: Serotype G295% CI: [0.99, 1.33]
Comparison: Serotype G395% CI: [2.75, 3.74]
Comparison: Serotype G495% CI: [0.94, 1.2]
Comparison: Serotype P1A\[8\]95% CI: [1, 1.35]
Secondary
Geometric Mean Titer of Serum Anti-Rotavirus Immunoglobulin A
Time frame: 42 days after vaccination 3 (up to 185 days)
Population: Participants who received the 3 scheduled doses of study vaccine, did not have important protocol deviations, and had follow-up results for the endpoint
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| RotaTeq™ Experimental Formulation | Geometric Mean Titer of Serum Anti-Rotavirus Immunoglobulin A | 240.5 Titer |
| RotaTeq™ Existing Formulation | Geometric Mean Titer of Serum Anti-Rotavirus Immunoglobulin A | 235.5 Titer |
Secondary
Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability
An adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an adverse event. Protocol-defined Tier-1 adverse events to be collected up to 7 days after any vaccination were diarrhea, vomiting, elevated temperature (rectal \>=38.1° C, \>=100.5° F), and irritability.
Time frame: Up to 7 days after any vaccination (up to 147 days)
Population: Participants who received at least one dose of study vaccine. Participants were assigned to treatment groups based on the vaccine received as the first dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RotaTeq™ Experimental Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Diarrhea | 144 Participants |
| RotaTeq™ Experimental Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Vomiting | 84 Participants |
| RotaTeq™ Experimental Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Elevated temperature | 217 Participants |
| RotaTeq™ Experimental Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Irritability | 58 Participants |
| RotaTeq™ Existing Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Irritability | 64 Participants |
| RotaTeq™ Existing Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Diarrhea | 128 Participants |
| RotaTeq™ Existing Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Elevated temperature | 223 Participants |
| RotaTeq™ Existing Formulation | Number of Participants With Tier-1 Adverse Events: Diarrhea, Vomiting, Elevated Temperature, and Irritability | Vomiting | 92 Participants |
Secondary
Number of Participants With Tier-1 Adverse Events: Intussusception
The protocol-defined Tier-1 adverse event to be collected for the duration of the study (up to Day 185) was intussusception
Time frame: Up to Day 185
Population: Participants who received at least one dose of study vaccine. Participants were assigned to treatment groups based on the vaccine received as the first dose.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RotaTeq™ Experimental Formulation | Number of Participants With Tier-1 Adverse Events: Intussusception | 2 Participants |
| RotaTeq™ Existing Formulation | Number of Participants With Tier-1 Adverse Events: Intussusception | 0 Participants |
Secondary
Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]
Time frame: Baseline and 42 days after vaccination 3 (up to 185 days)
Population: Participants who received the 3 scheduled doses of study vaccine, did not have important protocol deviations, and had baseline and follow-up results for the endpoint
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RotaTeq™ Experimental Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G2 | 30.4 Percentage of participants |
| RotaTeq™ Experimental Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G4 | 58.3 Percentage of participants |
| RotaTeq™ Experimental Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G3 | 65.8 Percentage of participants |
| RotaTeq™ Experimental Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype P1A[8] | 49.6 Percentage of participants |
| RotaTeq™ Experimental Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G1 | 56.0 Percentage of participants |
| RotaTeq™ Existing Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype P1A[8] | 42.6 Percentage of participants |
| RotaTeq™ Existing Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G1 | 53.8 Percentage of participants |
| RotaTeq™ Existing Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G2 | 26.8 Percentage of participants |
| RotaTeq™ Existing Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G3 | 33.3 Percentage of participants |
| RotaTeq™ Existing Formulation | Percentage of Participants With >=3-fold Rise From Baseline in GMT of Serum Neutralizing Antibody to Human Rotavirus Serotypes G1, G2, G3, G4, and P1A[8] | Serotype G4 | 49.7 Percentage of participants |