Rotavirus Gastroenteritis
Conditions
Brief summary
This study will assess the safety and tolerability of RotaTeq™ (V260) in the healthy Chinese populations. Approximately 144 participants will be enrolled and equally stratified into three age cohorts, Cohort I ages 19-47 years, Cohort II ages 2-6 years, and Cohort III ages 6-12 weeks. Randomization ratio is 1:1 in each cohort. The study will be conducted sequentially, participants in Cohort I then Cohort II receiving 1 dose of, and then participants in Cohort III receiving 3 doses of RotaTeq™/placebo. The primary investigator and the Ethics Review Committee will review blinded safety data and make decision based on their best clinical judgment to move study forward between cohorts. Duration for the entire study will be approximately 6-9 months.
Interventions
Single 2.0 mL dose V260 (RotaTeq™) administered orally at enrollment. The 2-mL vaccine consists of an oral solution of 5 live human-bovine reassortant rotaviruses.
BIOLOGICALComparator: Placebo
Single 2.0 mL dose of matching placebo to RotaTeq™ administered orally at enrollment.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 47 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adults ages 19 to 47 years for Cohort I * Healthy children ages 2 to 6 years for Cohort II * Healthy infants ages 6 to 12 weeks for Cohort III * Negative pregnancy test for females in Cohort I * Signed Informed Consent Forms (ICFs)
Exclusion criteria
* Participants in Cohorts I and II receiving any vaccine 14 days before or anticipated after study vaccine * Participants in Cohort III receiving non-concomitant live vaccines 14 days before or after study vaccine * Prior administration of any rotavirus vaccine * Elevated temperature, with axillary temperature ≥37.1 Degrees C 24 hours before study vaccine * Prior or active gastrointestinal illnesses, immunodeficiency * Any condition which may interfere with evaluation of study objectives or make participation in the study unsafe for the participant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events | up to 14 days post vaccination | All serious adverse events (SAEs) were collected for 14 days following each dose to obtain the number of participants with serious adverse events. |
| Number of Serious Adverse Events | 14 days post vaccination | The total number of serious adverse experiences (events) in participants up to 14 days post vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Infants With Fecal Vaccine Virus Shedding | Between Day 3 and Day 7 following each of 3 doses of RotaTeq™/placebo | Fecal shedding of vaccine rotavirus in Cohort III (infants) was evaluated by determining the number of participants whose stool was positive by both (1) the Enzyme-linked Immunosorbent Assay (EIA) to detect the rotavirus antigen, and (2) PCR VP6 Genotyping (a polymerase chain reaction assay specific for rotavirus genome 6, coding for the VP6 protein of the vaccine virus). For analysis, two stool samples were collected per participant on separate days between Day 3 and Day 7 following each vaccination dose. |
Participant flow
Recruitment details
A total of 144 participants were enrolled; 48 in each of 3 cohorts. This study was conducted sequentially in the 3 different Cohorts, Chinese adults (Cohort I) first, followed by children (Cohort II), and then infants (Cohort III).
Participants by arm
| Arm | Count |
|---|---|
| Cohort I - RotaTeq™, Adults Adults randomized to receive a single dose of RotaTeq™. | 24 |
| Cohort I - Placebo, Adults Adults randomized to receive a single dose of matching placebo to RotaTeq™. | 24 |
| Cohort II - RotaTeq™, Children Children randomized to receive a single dose of RotaTeq™. | 24 |
| Cohort II - Placebo, Children Children randomized to receive a single dose of matching placebo to RotaTeq™. | 24 |
| Cohort III - RotaTeq™, Infants Infants randomized to receive 3 doses of RotaTeq™. | 24 |
| Cohort III - Placebo, Infants Infants randomized to receive 3 doses of matching placebo to RotaTeq™. | 24 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Serious Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew Consent | 0 | 0 | 0 | 0 | 2 | 3 |
Baseline characteristics
| Characteristic | Total | Cohort III - Placebo, Infants | Cohort III - RotaTeq™, Infants | Cohort I - RotaTeq™, Adults | Cohort II - Placebo, Children | Cohort II - RotaTeq™, Children | Cohort I - Placebo, Adults |
|---|---|---|---|---|---|---|---|
| Age, Customized 19 years to 49 years (adults) | 48 participants | 0 participants | 0 participants | 24 participants | 0 participants | 0 participants | 24 participants |
| Age, Customized 2 years to 5 years (children) | 48 participants | 0 participants | 0 participants | 0 participants | 24 participants | 24 participants | 0 participants |
| Age, Customized 6 weeks to 12 weeks (infants) | 48 participants | 24 participants | 24 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment China | 144 participants | 24 participants | 24 participants | 24 participants | 24 participants | 24 participants | 24 participants |
| Sex: Female, Male Female | 70 Participants | 11 Participants | 8 Participants | 13 Participants | 11 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 74 Participants | 13 Participants | 16 Participants | 11 Participants | 13 Participants | 14 Participants | 7 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 | 6 / 24 | 2 / 24 | 6 / 24 | 3 / 24 | 18 / 24 | 14 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 0 / 24 | 3 / 24 |
Outcome results
Primary
Number of Participants With Serious Adverse Events
All serious adverse events (SAEs) were collected for 14 days following each dose to obtain the number of participants with serious adverse events.
Time frame: up to 14 days post vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - RotaTeq™, Adults | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort I - Placebo, Adults | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort II - RotaTeq™, Children | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort II - Placebo, Children | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort III - RotaTeq™, Infants | Number of Participants With Serious Adverse Events | 0 Participants |
| Cohort III - Placebo, Infants | Number of Participants With Serious Adverse Events | 3 Participants |
Primary
Number of Serious Adverse Events
The total number of serious adverse experiences (events) in participants up to 14 days post vaccination.
Time frame: 14 days post vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort I - RotaTeq™, Adults | Number of Serious Adverse Events | 0 Events |
| Cohort I - Placebo, Adults | Number of Serious Adverse Events | 0 Events |
| Cohort II - RotaTeq™, Children | Number of Serious Adverse Events | 0 Events |
| Cohort II - Placebo, Children | Number of Serious Adverse Events | 0 Events |
| Cohort III - RotaTeq™, Infants | Number of Serious Adverse Events | 0 Events |
| Cohort III - Placebo, Infants | Number of Serious Adverse Events | 4 Events |
Secondary
Number of Infants With Fecal Vaccine Virus Shedding
Fecal shedding of vaccine rotavirus in Cohort III (infants) was evaluated by determining the number of participants whose stool was positive by both (1) the Enzyme-linked Immunosorbent Assay (EIA) to detect the rotavirus antigen, and (2) PCR VP6 Genotyping (a polymerase chain reaction assay specific for rotavirus genome 6, coding for the VP6 protein of the vaccine virus). For analysis, two stool samples were collected per participant on separate days between Day 3 and Day 7 following each vaccination dose.
Time frame: Between Day 3 and Day 7 following each of 3 doses of RotaTeq™/placebo
Population: Only participants in Cohort III, infants that received the scheduled dose of vaccination, and for whom the stool samples were available for testing, were included in the analysis for that dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort I - RotaTeq™, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 1 (n=23 for RotaTeq™, n=24 for placebo) | 3 Participants |
| Cohort I - RotaTeq™, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 2 (n=21 for RotaTeq™, n=22 for placebo) | 2 Participants |
| Cohort I - RotaTeq™, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 3 (n=22 for RotaTeq™, n=20 for placebo) | 3 Participants |
| Cohort I - Placebo, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 1 (n=23 for RotaTeq™, n=24 for placebo) | 0 Participants |
| Cohort I - Placebo, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 2 (n=21 for RotaTeq™, n=22 for placebo) | 0 Participants |
| Cohort I - Placebo, Adults | Number of Infants With Fecal Vaccine Virus Shedding | Postdose 3 (n=22 for RotaTeq™, n=20 for placebo) | 0 Participants |