Diarrhea, Gastroenteritis
Conditions
Keywords
Gastroenteritis, Diarrhea, Rotavirus, Vaccine, Dehydration
Brief summary
This is a pilot study to assess the safety and immunogenicity of pentavalent rotavirus vaccine (RV5) when administered according to an alternate dosing schedule (2-5 weeks, 2 months and 4 months). In this interventional, open-label study, infants 2 through 5 weeks of age (14 to 41 days) will be enrolled and vaccinated with RV5 according to a 2-5 week, 2 and 4 month schedule and infants 2 months of age (56 to 83 days) will be vaccinated according to the standard recommended schedule (2, 4, and 6 months of age). Sera will be obtained from subjects one month following the final dose of vaccine and will be assayed for anti-rotavirus IgA and rotavirus neutralizing antibody responses against the G1, G2, G3, G4 and P\[8\] serotypes. Post dose 3 G1 serum-neutralizing antibody (SNA) geometric mean titers (GMTs) will be compared between children receiving pentavalent rotavirus vaccine (RV5) according to the alternate dosing schedule versus the standard recommended schedule. Likewise, post dose 3 G2, G3, G4 and P\[8\] SNA and serum rotavirus IgA GMTs will be compared between children receiving RV5 according to the alternate dosing schedule and the standard recommended schedule. The safety and tolerability of RV5 in children receiving vaccine according to the alternate dosing schedule will be described.
Interventions
BIOLOGICALRV5 (Pentavalent Rotavirus Vaccine)
Sponsors
Merck Sharp & Dohme LLC
Dennis Clements
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
14 Days to 83 Days
Healthy volunteers
Yes
Inclusion criteria
1. Male or female infants who are 14 through 41 or 56 through 83 days of age at Visit 1 (Day of initial vaccination) 2. Parent / legal guardian has read and signed the informed consent document 3. Child and parent / legal guardian is available for the entire study period and can be reached by telephone 4. Healthy infant as determined by medical history and by a baseline physical examination 5. Infant weight at time of enrollment must exceed birth weight
Exclusion criteria
1. History of hypersensitivity to the vaccine or any component of the vaccine 2. History of Severe Combined Immunodeficiency Disease (SCID) 3. History of immunocompromise ( infant is known to be HIV positive, to have hypogammaglobulinemia or to have an underlying malignancy) 4. History of intussusception 5. Any clinically significant history of gastrointestinal disease including active acute gastrointestinal illness, chronic diarrhea, failure to thrive, congenital abdominal disorders, abdominal surgery or liver disease 6. Prior receipt of a rotavirus vaccine 7. Less than 37 weeks gestation 8. The subject has participated in a study with an experimental agent within one month of enrollment in the study or anticipated receipt of an experimental agent during participation in the study 9. Receipt of blood products within 4 weeks of study vaccination 10. Receipt of a live virus vaccine within 4 weeks of study vaccination or an inactivated vaccine within 2 weeks. Concomitant administration of routinely recommended vaccines is allowed. A dose of hepatitis B vaccine administered in the birthing hospital is permitted. Planned routine use of inactivated influenza vaccine for children over 6 months of age is permitted. 11. Acute illness within 48 hours of vaccination (axillary temperature of 100.4°F or higher, 3 or more grossly watery stools, vomiting). (Infants with stable unchanged gastroesophageal reflux may be enrolled). 12. Insufficient weight gain requiring future weight checks in addition to routine scheduled well child visits 13. The subject has any condition that the investigator believes would put the subject at an increased risk of injury or would render the subject unable to complete the trial or fulfill the requirements of the study protocol. 14. Household contact who is immunodeficient (any malignancies or otherwise immunocompromised, primary immunodeficiency, receiving immunosuppressive therapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| G1 Serum-neutralizing Antibody | 1 month following vaccine series completion | Post dose 3 G1 serum-neutralizing antibody (SNA) geometric mean titer (GMT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| G2 Serum-neutralizing Antibody | 1 month following vaccine series completion | Post dose 3 G2 serum-neutralizing antibody(SNA) geometric mean titer (GMT) |
| G3 Serum-neutralizing Antibody | 1 month following vaccine series completion | Post dose 3 G3 serum-neutralizing antibody(SNA) geometric mean titer (GMT) |
| G4 Serum-neutralizing Antibody | 1 month following vaccine series completion | Post dose 3 G4 serum-neutralizing antibody(SNA) geometric mean titer (GMT) |
| P1 Serum-neutralizing Antibody | 1 month following vaccine series completion | Post dose 3 P1 serum-neutralizing antibody(SNA) geometric mean titer (GMT) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reactogenicity Assessment | 7 days after each dose, up to 10 months post-vaccination | Proportions of subjects in each vaccine group reporting a reactogenicity event in the period following each dose and any dose of RV5 will be determined |
| Adverse Event Assessment | 28 days after each dose, up to 10 months post-vaccination | Proportions of subjects in each vaccine group reporting an adverse event in the period following each dose and any dose of RV5 will be determined |
| Serious Adverse Event Assessment | After each dose and up to 10 months post-vaccination | Proportions of subjects in each vaccine group reporting an adverse event in the period following each dose and any dose of RV5 will be determined |
| Serum Rotavirus Immunoglobulin A | 1 month following vaccine series completion | Post dose 3 serum rotavirus Immunoglobulin A geometric mean titer (GMT) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A: Standard Dosing Group will receive RV5 vaccine at 2, 4, and 6 months of age
RV5 (Pentavalent Rotavirus Vaccine) | 33 |
| Group B: Alternate Dosing Group will receive RV5 vaccine at 2-5 weeks, 2 and 4 months of age
RV5 (Pentavalent Rotavirus Vaccine) | 33 |
| Total | 66 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 4 | 3 |
| Overall Study | unable to obtain blood sample | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Group B: Alternate Dosing | Total | Group A: Standard Dosing |
|---|---|---|---|
| Age, Continuous | 26.6 days STANDARD_DEVIATION 7.3 | 44.8 days STANDARD_DEVIATION 19.3 | 63 days STANDARD_DEVIATION 4.6 |
| Race/Ethnicity, Customized African American | 4 participants | 13 participants | 9 participants |
| Race/Ethnicity, Customized Asian | 2 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic | 3 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Non-Hispanic | 30 participants | 60 participants | 30 participants |
| Race/Ethnicity, Customized White | 27 participants | 51 participants | 24 participants |
| Sex: Female, Male Female | 21 Participants | 40 Participants | 19 Participants |
| Sex: Female, Male Male | 12 Participants | 26 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 33 | 17 / 33 |
| serious Total, serious adverse events | 1 / 33 | 0 / 33 |
Outcome results
Primary
G1 Serum-neutralizing Antibody
Post dose 3 G1 serum-neutralizing antibody (SNA) geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | G1 Serum-neutralizing Antibody | 188 titers |
| Group B: Alternate Dosing | G1 Serum-neutralizing Antibody | 184.5 titers |
Secondary
G2 Serum-neutralizing Antibody
Post dose 3 G2 serum-neutralizing antibody(SNA) geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | G2 Serum-neutralizing Antibody | 38.7 titers |
| Group B: Alternate Dosing | G2 Serum-neutralizing Antibody | 33.1 titers |
Secondary
G3 Serum-neutralizing Antibody
Post dose 3 G3 serum-neutralizing antibody(SNA) geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | G3 Serum-neutralizing Antibody | 42.1 titers |
| Group B: Alternate Dosing | G3 Serum-neutralizing Antibody | 27.3 titers |
Secondary
G4 Serum-neutralizing Antibody
Post dose 3 G4 serum-neutralizing antibody(SNA) geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | G4 Serum-neutralizing Antibody | 144.6 titers |
| Group B: Alternate Dosing | G4 Serum-neutralizing Antibody | 66.5 titers |
Secondary
P1 Serum-neutralizing Antibody
Post dose 3 P1 serum-neutralizing antibody(SNA) geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | P1 Serum-neutralizing Antibody | 114.7 titers |
| Group B: Alternate Dosing | P1 Serum-neutralizing Antibody | 136.5 titers |
Other Pre-specified
Adverse Event Assessment
Proportions of subjects in each vaccine group reporting an adverse event in the period following each dose and any dose of RV5 will be determined
Time frame: 28 days after each dose, up to 10 months post-vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: Standard Dosing | Adverse Event Assessment | Post dose 1 | 0.27 Proportion of participants |
| Group A: Standard Dosing | Adverse Event Assessment | Post dose 2 | 0.06 Proportion of participants |
| Group A: Standard Dosing | Adverse Event Assessment | Post dose 3 | 0.03 Proportion of participants |
| Group A: Standard Dosing | Adverse Event Assessment | Post any dose | 0.30 Proportion of participants |
| Group B: Alternate Dosing | Adverse Event Assessment | Post any dose | 0.51 Proportion of participants |
| Group B: Alternate Dosing | Adverse Event Assessment | Post dose 1 | 0.51 Proportion of participants |
| Group B: Alternate Dosing | Adverse Event Assessment | Post dose 3 | 0.06 Proportion of participants |
| Group B: Alternate Dosing | Adverse Event Assessment | Post dose 2 | 0.09 Proportion of participants |
Other Pre-specified
Reactogenicity Assessment
Proportions of subjects in each vaccine group reporting a reactogenicity event in the period following each dose and any dose of RV5 will be determined
Time frame: 7 days after each dose, up to 10 months post-vaccination
Population: Proportions of subjects in each vaccine group reporting a reactogenicity event in the period following each dose and any does of RV5 will be determined
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: Standard Dosing | Reactogenicity Assessment | Fever | 0.06 Proportion of participants |
| Group A: Standard Dosing | Reactogenicity Assessment | Vomiting | 0.15 Proportion of participants |
| Group A: Standard Dosing | Reactogenicity Assessment | Diarrhea | 0.21 Proportion of participants |
| Group B: Alternate Dosing | Reactogenicity Assessment | Fever | 0.03 Proportion of participants |
| Group B: Alternate Dosing | Reactogenicity Assessment | Vomiting | 0.24 Proportion of participants |
| Group B: Alternate Dosing | Reactogenicity Assessment | Diarrhea | 0.39 Proportion of participants |
Other Pre-specified
Serious Adverse Event Assessment
Proportions of subjects in each vaccine group reporting an adverse event in the period following each dose and any dose of RV5 will be determined
Time frame: After each dose and up to 10 months post-vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A: Standard Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 1 | 0 Proportion of participants |
| Group A: Standard Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 2 | 0 Proportion of participants |
| Group A: Standard Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 3 | 0.03 Proportion of participants |
| Group B: Alternate Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 1 | 0 Proportion of participants |
| Group B: Alternate Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 2 | 0 Proportion of participants |
| Group B: Alternate Dosing | Serious Adverse Event Assessment | Serious Adverse Event-Post dose 3 | 0 Proportion of participants |
Other Pre-specified
Serum Rotavirus Immunoglobulin A
Post dose 3 serum rotavirus Immunoglobulin A geometric mean titer (GMT)
Time frame: 1 month following vaccine series completion
Population: The per protocol analysis population includes participants who met all inclusion and exclusion criteria, received all scheduled study vaccinations, and who contributed post-vaccination blood samples for testing for which valid results were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Group A: Standard Dosing | Serum Rotavirus Immunoglobulin A | 318.3 titers |
| Group B: Alternate Dosing | Serum Rotavirus Immunoglobulin A | 183.7 titers |