Prevention of Rotavirus Gastroenteritis in Infants and Children Caused by Serotypes G1, G2, G3, G4, and G9
Conditions
Brief summary
This study will evaluate the immunogenicity and safety of concomitant administration of RotaTeq® (V260) and inactivated poliomyelitis vaccine (IPV) in Chinese infants. Its primary objective is to demonstrate that the immunogenicity of IPV in the concomitant-use group is non-inferior to the immunogenicity of IPV in the staggered-use group. The hypothesis to be tested is: The seroconversion percentage at 1 month post dose 3 for poliovirus types 1, 2, and 3 in the concomitant-use group is non-inferior to those of the staggered-use group.
Interventions
BIOLOGICALRotaTeq (V260)
Live, pentavalent rotavirus vaccine administered as a 2 mL-dose oral solution
BIOLOGICALIPV
0.5 mL dose IPV (Sabin strain based), administered via IM injection
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
48 Days to 63 Days
Healthy volunteers
Yes
Inclusion criteria
* Healthy Chinese infant 48 days to 63 days of age. * Infant's legally acceptable representative provides written informed consent for the study.
Exclusion criteria
* History of rotavirus disease, congenital gastrointestinal disorders, chronic diarrhea, failure to thrive, or abdominal surgery. * History of intussusception. * History of poliomyelitis. * Clinical evidence of active gastrointestinal illness. Note: Infants with gastroesophageal reflux disease \[GERD\] may participate in the study if the GERD is well controlled with or without medication. * Known or suspected impairment of immunological function, including severe combined immunodeficiency disease (SCID). * Has a fever, with an axillary temperature ≥37.5°C (or equivalent) at the time of vaccination or within 24 hours prior to vaccination. Note: The Visit 1 may be rescheduled after complete resolution of febrile illness. * Has acute disease. * Has underlying diseases such as cardiovascular, renal, liver, or blood disease. * History of known hypersensitivity to any components of rotavirus vaccine and/or IPV. * Uncontrolled epilepsy, encephalopathy, seizure, or other progressive neurological diseases. * Known thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections. * Resides in a household with an immunocompromised person, including individuals with congenital immunodeficiency (including SCID), human immunodeficiency virus (HIV) infection, leukemia, lymphoma, multiple myeloma, generalized malignance, chronic renal failure, organ or bone marrow transplantation, or with those receiving immunosuppressive chemotherapy including long-term systemic corticosteroids. * Any condition, which in the opinion of the investigator, may interfere with the evaluation of the study objectives. * Prior administration of any rotavirus vaccines or poliovirus vaccines. * Has received inactivated or recombinant vaccines within 14 days prior to Visit 1 or live vaccines within 28 days prior to Visit 1. * Has received an investigational or non-registered product other than study vaccines or is planning to use such product during the study. * Has received immunosuppressive therapies including systemic (intramuscular, oral, or intravenous) corticosteroids. Note: Participants using non-systemic corticosteroids (e.g., topical, ophthalmic, and inhaled) are considered eligible for the study. * Has received a blood transfusion or blood products, including immunoglobulins or is planning to receive such product during the study. * Has participated in another interventional study prior to Visit 1 or expected to anytime during the study. * The infant's legally acceptable representative is unlikely to adhere to the study procedures, keep appointments or is planning to permanently relocate from the area prior to the completion of the study or to leave for an extended period when study visits would need to be scheduled. * Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is an investigational site or Sponsor staff member directly involved with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Baseline and 1 month postdose 3 of IPV (Month ~3.5) | The immunogenicity of IPV was measured using poliovirus serum neutralizing antibody assay of the National Institutes for Food and Drug Control (NIFDC), Beijing, China. Serum conversion was defined as antibody titer ≥1:8 post-vaccination in baseline seronegative participants or ≥4-fold increase in titer post-vaccination in baseline seropositive participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | 1 month post dose 3 of IPV (Month ~3.5) | The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China. |
| Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | 1 month postdose 3 of IPV (Month ~3.5) | The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China. |
| Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | 1 month postdose 3 of IPV (Month ~3.5) | The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China. |
| Percentage of Participants With Solicited Systemic Adverse Events | Up to 7 days following each RotaTeq and/or IPV vaccination | Solicited systemic AEs included diarrhea, vomiting, and elevated temperature (axillary temperature ≥37.5º C). |
| Percentage of Participants With Serious Adverse Events (SAEs) | Up to approximately 3.5 months | The percentage of participants with SAEs is presented. An SAE is an AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or another important medical event. |
| Percentage of Participants With Solicited Injection-Site Adverse Events | Up to 7 days following each IPV vaccination | Solicited injection-site adverse events (AEs) included erythema, swelling, induration, and pain at the IPV injection-site. |
Countries
China
Participant flow
Pre-assignment details
This study was conducted at a study center in China.
Participants by arm
| Arm | Count |
|---|---|
| Concomitant RotaTeq and IPV Participants will receive RotaTeq (2 mL oral dose) and IPV (0.5 mL intramuscular \[IM\] injection ) concomitantly at Visit 2 (15 to 21 days after Visit 1 \[Day 1\]), Visit 4 (30 to 42 days after Visit 2), and Visit 6 (30 to 42 days after Visit 4). | 200 |
| Staggered RotaTeq and IPV Participants will receive RotaTeq (2 mL oral dose) at Visit 1 (Day 1), Visit 3 (30 to 42 days after Visit 1), and Visit 5 (30 to 42 days after Visit 3); and IPV (0.5 mL IM injection) at Visit 2 (15 to 21 days Visit 1), Visit 4 (30 to 42 days after Visit 2), and Visit 6 (30 to 42 days after Visit 4). | 200 |
| Total | 400 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawn by parent/guardian | 15 | 10 |
Baseline characteristics
| Characteristic | Concomitant RotaTeq and IPV | Staggered RotaTeq and IPV | Total |
|---|---|---|---|
| Age, Continuous | 53.3 days STANDARD_DEVIATION 4.8 | 53.3 days STANDARD_DEVIATION 4.6 | 53.3 days STANDARD_DEVIATION 4.7 |
| Age, Customized Infants and toddlers (48 to 63 days) | 200 Participants | 200 Participants | 400 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants | 200 Participants | 400 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 200 Participants | 200 Participants | 400 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 86 Participants | 93 Participants | 179 Participants |
| Sex: Female, Male Male | 114 Participants | 107 Participants | 221 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 189 | 0 / 200 |
| other Total, other adverse events | 123 / 189 | 143 / 200 |
| serious Total, serious adverse events | 7 / 189 | 11 / 200 |
Outcome results
Primary
Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV
The immunogenicity of IPV was measured using poliovirus serum neutralizing antibody assay of the National Institutes for Food and Drug Control (NIFDC), Beijing, China. Serum conversion was defined as antibody titer ≥1:8 post-vaccination in baseline seronegative participants or ≥4-fold increase in titer post-vaccination in baseline seropositive participants.
Time frame: Baseline and 1 month postdose 3 of IPV (Month ~3.5)
Population: Participants who received the 3 scheduled doses of study vaccination, adhered to guidelines for vaccine administration, provided baseline and post-vaccination blood samples within the acceptable day range, and did not have important protocol deviations are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 98.9 Percentage of Participants |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 98.3 Percentage of Participants |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 100.0 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 100.0 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 99.5 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Seroconversion to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 99.5 Percentage of Participants |
Comparison: Difference indicates Concomitant-use Group % - Staggered-use Group %p-value: <0.00195% CI: [-4, 0.9]Unstratified Miettinen & Nurminen method
Comparison: Difference indicates Concomitant-use Group % - Staggered-use Group %p-value: <0.00195% CI: [-4.3, 1.5]Unstratified Miettinen & Nurminen method
Comparison: Difference indicates Concomitant-use % - Staggered-use %p-value: <0.00195% CI: [-1.6, 3]Unstratified Miettinen & Nurminen method
Secondary
Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV
The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China.
Time frame: 1 month postdose 3 of IPV (Month ~3.5)
Population: Participants who received the 3 scheduled doses of study vaccination, adhered to guidelines for vaccine administration, provided baseline and post-vaccination blood samples within the acceptable day range, and did not have important protocol deviations are included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Concomitant RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 5600.80 Titers | 95% Confidence Interval 4898.46 |
| Concomitant RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 1059.83 Titers | 95% Confidence Interval 951.13 |
| Concomitant RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 3405.56 Titers | 95% Confidence Interval 3033.93 |
| Staggered RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 5344.24 Titers | 95% Confidence Interval 4657.51 |
| Staggered RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 1122.43 Titers | 95% Confidence Interval 1002.74 |
| Staggered RotaTeq and IPV | Geometric Mean Titers (GMTs) of Neutralizing Antibody to Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 3261.69 Titers | 95% Confidence Interval 2913.7 |
Secondary
Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV
The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China.
Time frame: 1 month postdose 3 of IPV (Month ~3.5)
Population: Participants who received the 3 scheduled doses of study vaccination, adhered to guidelines for vaccine administration, provided baseline and post-vaccination blood samples within the acceptable day range, and did not have important protocol deviations are included.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 100.00 Percentage of Participants | 95% Confidence Interval 98 |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:64 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
Secondary
Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV
The immune response to IPV was measured using poliovirus serum neutralizing antibody assay of the NIFDC, Beijing, China.
Time frame: 1 month post dose 3 of IPV (Month ~3.5)
Population: Participants who received the 3 scheduled doses of study vaccination, adhered to guidelines for vaccine administration, provided baseline and post-vaccination blood samples within the acceptable day range, and did not have important protocol deviations are included.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Concomitant RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 1 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 2 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
| Staggered RotaTeq and IPV | Percentage of Participants Achieving Neutralizing Antibody Titers ≥1:8 for Poliovirus Types 1, 2, and 3 at 1 Month Post Dose 3 of IPV | Poliovirus Type 3 | 100.0 Percentage of Participants | 95% Confidence Interval 98 |
Secondary
Percentage of Participants With Serious Adverse Events (SAEs)
The percentage of participants with SAEs is presented. An SAE is an AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or another important medical event.
Time frame: Up to approximately 3.5 months
Population: All participants who received ≥1 dose of study treatment are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants With Serious Adverse Events (SAEs) | 3.7 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants With Serious Adverse Events (SAEs) | 5.5 Percentage of Participants |
Secondary
Percentage of Participants With Solicited Injection-Site Adverse Events
Solicited injection-site adverse events (AEs) included erythema, swelling, induration, and pain at the IPV injection-site.
Time frame: Up to 7 days following each IPV vaccination
Population: All participants who received ≥1 dose of study treatment are included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants With Solicited Injection-Site Adverse Events | 25.4 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants With Solicited Injection-Site Adverse Events | 23.0 Percentage of Participants |
Secondary
Percentage of Participants With Solicited Systemic Adverse Events
Solicited systemic AEs included diarrhea, vomiting, and elevated temperature (axillary temperature ≥37.5º C).
Time frame: Up to 7 days following each RotaTeq and/or IPV vaccination
Population: All participants who received ≥1 dose of study treatment and have data available are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Concomitant RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Elevated temperature | 12.3 Percentage of Participants |
| Concomitant RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Diarrhoea | 13.2 Percentage of Participants |
| Concomitant RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Vomiting | 10.6 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Elevated temperature | 16.3 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Diarrhoea | 21.5 Percentage of Participants |
| Staggered RotaTeq and IPV | Percentage of Participants With Solicited Systemic Adverse Events | Vomiting | 19.5 Percentage of Participants |