Rotavirus Infections
Conditions
Keywords
brazilian pentavalent rotavirus vaccine, safety, tolerability, immunogenicity
Brief summary
The purpose of this study is to describe the safety, tolerability and immunogenicity of the pentavalent rotavirus vaccine produced by Butantan Institute.
Detailed description
The Brazilian National Immunization Program (PNI) has introduced a oral monovalent vaccine against rotavirus for infants in its immunization schedule since 2006. Its introduction increased the Brazilian Ministry of Health budget because the vaccination in Brazil is free of charge. An agreement between Path Foundation and Butantan Institute has made possible the transfer of technology to Butantan Institute to produce, at a reduced cost, a pentavalent rotavirus vaccine including the the rotavirus serotypes more frequent in Brazil.
Interventions
BIOLOGICALrotavirus vaccine
3 doses with 6 weeks interval
BIOLOGICALplacebo
3 doses with 6 weeks interval
Sponsors
Butantan Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Male healthy * Age ≥18-40 years * Not taking immunosuppressive drugs * No clinical history of gastrointestinal diseases or surgeries * No history of cardiac, neurologic, immunologic or endocrine diseases * Normal eligibility laboratory tests * To be willing to participate and sign the informed consent form * No participation in another clinical trial in the past 6 months
Exclusion criteria
* Had received any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events. | Within the first five days post-vaccination. | Safety and tolerability were evaluated by monitoring occurence of fever, diarrhea, vomiting, abdominal pain and increase of liver enzymes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-rotavirus IgA Level. | before each dose (total of doses:3) and after 6 weeks of the third dose | It was evaluated by anti-rotavirus IgA levels in terms of optical density. Pre-vaccination levels of anti-rotavirus antibodies were not considered as an exclusion criterion. Seroconversion was considered as a fourfold increase in IgA titers. The proportion of seroconverters in both groups was compared. IgA levels in optical density were not converted to any unit of measure. |
Countries
Brazil
Participant flow
Recruitment details
Recruitment period: From February to August 2009.79 healthy adult volunteers from 18 to 40 years of age were selected. Participants were screened for eligibility and enrolled by the investigators following the signing of an informed consent. Due to a recommendation from ANVISA, female volunteers were not allowed to be recruited.
Pre-assignment details
98 potential volunteers were interviewed, 80 of them were enrolled: 40 volunteers were allocated to receive the investigational product (rotavirus vaccine) and 40 were allocated to receive placebo; 79 completed the follow-up. Before randomization 18 volunteers were excluded, 3 refused to participate and 15 had screening failure
Participants by arm
| Arm | Count |
|---|---|
| Rotavirus Vaccine 3 doses with 6 weeks interval | 40 |
| Placebo 3 doses with 6 weeks interval | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Rotavirus Vaccine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 40 Participants | 80 Participants |
| Age Continuous | 29.2 years STANDARD_DEVIATION 6.6 | 28.2 years STANDARD_DEVIATION 6.2 | 28.7 years STANDARD_DEVIATION 6.2 |
| Region of Enrollment Brazil | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 40 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 39 | 9 / 40 |
| serious Total, serious adverse events | 0 / 39 | 0 / 40 |
Outcome results
Primary
Number of Participants With Adverse Events.
Safety and tolerability were evaluated by monitoring occurence of fever, diarrhea, vomiting, abdominal pain and increase of liver enzymes.
Time frame: Within the first five days post-vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rotavirus Vaccine | Number of Participants With Adverse Events. | 14 participants |
| Placebo | Number of Participants With Adverse Events. | 12 participants |
Secondary
Anti-rotavirus IgA Level.
It was evaluated by anti-rotavirus IgA levels in terms of optical density. Pre-vaccination levels of anti-rotavirus antibodies were not considered as an exclusion criterion. Seroconversion was considered as a fourfold increase in IgA titers. The proportion of seroconverters in both groups was compared. IgA levels in optical density were not converted to any unit of measure.
Time frame: before each dose (total of doses:3) and after 6 weeks of the third dose
Population: As in most phase I trials, sample size was not calculated to provide statistically significant differences between groups. Rather, a descriptive analysis on the frequency of AE and immunogenicity data was undertaken.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rotavirus Vaccine | Anti-rotavirus IgA Level. | 0.51 Arbitrary units |
| Placebo | Anti-rotavirus IgA Level. | 0.35 Arbitrary units |