DiarrheaPhase 1/2NCT00439660
Dose Escalation Study to Evaluate Oral Rotavirus Vaccine 116E Live Attenuated in Healthy Infants 8 to 20 Weeks Old
A Phase 1/2 study testing Oral Rotavirus Vaccine 116E Live Attenuated in people with Diarrhea, run by Bharat Biotech International Limited at 1 site in India.
Trial summary
This study will be a Phase I, randomized, double blind, safety and immunogenicity trial of the Vero cell based 116E neonatal rotavirus vaccine candidate strain in healthy non-malnourished infants aged 8-20 weeks at three different dosage levels i.e.10^4.0, 10^5.0 and 10^6.0 FFU and for three administrations of each of… Read more about this study
- Who is it for?
- Ages 8 to 20 weeksHealthy volunteers can take part
- Conditions the study is for
- Diarrhea
- What is being tested?
- Oral Rotavirus Vaccine 116E Live Attenuated
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 1 siteIndia
- Study dates
- Dec 2006to Nov 2008
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 20 weeks
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Access to telephone at home or in the immediate neighborhood.
- Healthy male and female non-malnourished (weight for length not ≤ -3 SD of WHO child growth standards) infants aged 6 weeks (till 6 weeks + 2 days).
- Parent's permission to participate in the study is available.
- No plans to travel over the next 4 months
Who cannot join
- Gestational age <37 weeks.
- Any major physical congenital malformation.
- Living in a household or has contact with an individual who is immunosuppressed.
- Hospitalized once or more for the following illnesses since birth: heart disease, pneumonia, sepsis, meningitis, unconsciousness.
- Is required to take daily medications other than vitamins or herbal "tonics".
- Evidence of cardiovascular disease as indicated by any of the following:
Show all 33Show fewer
- Central cyanosis
- Cyanotic or apnoeic spells
- Features of congestive heart failure
- Significant heart murmur detected on physical examination
- Evidence of gastrointestinal disease indicated by following:
- Diarrhea in the previous 7 days
- Blood in the stools any time since birth
- Evidence of neurological disease, as indicated by:
- History of seizures any time since birth
- History of unconsciousness
- Focal deficit on physical examination
- Evidence of liver or other reticuloendothelial disease, as indicated by any of the following:
- Positive serology for hepatitis B surface antigen
- Positive serology for hepatitis C antibody
- SGOT or SGPT more than 1.25 times upper limit of normal (Upper limit normal SGOT 80 IU/L, SGPT 40 IU/L)
- Alkaline phosphatase more than 1.25 times upper limit of normal (Upper limit of normal -470 IU/L)
- Hepatomegaly (liver palpable 3 cm below costal margin), splenomegaly (palpable spleen), jaundice, or lymphadenopathy on physical examination
- Serum bilirubin 1.25 times the upper limit of normal for age (Upper limit of normal 1.0 mg/dL).
- Evidence of hematologic, rheumatologic, or immunologic disease, as indicated by any of the following:
- Total leukocyte count <3500 or >15,000/mm3
- Hemoglobin <9 g/dL or >17g/dL
- Platelet count <100,000/mm3
- Any episode of sepsis, pneumonia or meningitis requiring hospitalization since birth.
- Evidence of renal disease as indicated by any of the following:
- Creatinine >0.5 mg/dL
- Hematuria (≥5 RBC/hpf)
- Proteinuria (≥1+ per day)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-Blind Randomized Placebo-Controlled Dose Escalating Phase Ib/IIa Study to Evaluate the Safety and Immunogenicity of Live Attenuated Oral Rotavirus Vaccine 116E in Healthy Non-Malnourished Infants 8 to 20 Weeks of Age
This study will be a Phase I, randomized, double blind, safety and immunogenicity trial of the Vero cell based 116E neonatal rotavirus vaccine candidate strain in healthy non-malnourished infants aged 8-20 weeks at three different dosage levels i.e.10^4.0, 10^5.0 and 10^6.0 FFU and for three administrations of each of these dosages given to infants at 4-week intervals. 180 infants (90 vaccinees/90 placebo) will be enrolled for each of the three dosage levels. The progression from the lower to the next higher dosage will be based on approval by the Data Safety Monitoring Board (DSMB) to be constituted by the Department of Biotechnology, New Delhi.
Read the detailed description
Infants will be identified through a community survey in urban neighborhoods in the city of Delhi, India and screened at 6 weeks of age if parental consent is available. They will be given the first dose of EPI vaccines at this age. Of those screened, eligible infants will be given the first administration of the test vaccine/placebo at 8 weeks of age if they meet the enrollment inclusion criteria, and consent is available. The safety profile will be studied through daily home visits for 14 days post administration. Stool specimens will be collected before vaccination (day 0) and on days 3, 7 and 28 post administration of vaccine/placebo. Subsequently, two contacts will be made; a home visit on day 21 and a clinic visit on day 28. On the day 28 visit, a stool and blood specimen will be collected. Prior to each administration of vaccine/placebo the infants will be assessed for any contraindications.
All screened infants will be offered EPI vaccines as scheduled. The second and third administration of study vaccine/placebo will be at 12 and 16 weeks of age and the same strategy will be followed for each of the three dosages The study vaccine/placebo are not being administered with the EPI vaccines even though in the future rotavirus vaccine and the EPI vaccines may be coadministered. For the purpose of this study this schedule is being adopted, as no data are available on the interaction of EPI vaccines with this rotavirus vaccine candidate.
Baseline sera will be collected at 6 weeks (at the time of screening) and again 4 weeks after administration of the vaccine/placebo in a randomly selected subsample after the first (60 infants), second (60 infants) and third (60 infants) administration of each dosage.
Clinical adverse events will be monitored and relatedness to vaccine/placebo administration assessed for 14 days after each administration of the dosage under study, whereas monitoring for symptoms of intussusception will be assessed throughout the 28 day follow up period. Laboratory adverse events will be monitored for upto 28 days after first administration of each dosage. After the 4 week follow up of the third administration of the vaccine/placebo of the lowest dosage (10^4.0) is completed for all enrolled infants and the data safety monitoring board (DSMB) meeting will be convened and the data from the study will be analyzed, the code broken. If the DSMB declares the dosage safe, guided by the apriori criteria, the team will move on to screening infants for the next higher dosage (10^5.0) and the strategy listed above will be repeated for a total of 180 enrolled infants (90 vaccinees/90 placebo). The DSMB will again meet to review the data available from this cohort (i.e. 10^5.0) and the team will proceed to screen infants for the next higher dosage (10^6.0) only if the former is declared safe.
At the end of the study i.e. after the last visit of the last participant, based on reactogenicity and immunogenicity profile of each dosage, the appropriate dosage will be selected for further clinical evaluation.
- Conditions
- Diarrhea
- Being tested
- Oral Rotavirus Vaccine 116E Live Attenuated
- Keywords
- Rotavirus, diarrhea, vaccine
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Rotavirus Vaccine 116E Live AttenuatedBiological
| Study group | Role | What they receive |
|---|---|---|
| rotavirus vaccine 116E 1 X 10(4) | Experimental | vaccine dose of 1 X 10(4) focus-forming units (ffu) in three doses starting at 6 weeks : 4 weeks apart each dose Receives: Biological: Oral Rotavirus Vaccine 116E Live Attenuated |
| rotavirus vaccine 116E 1 X 10(5) | Experimental | vaccine dose of 1 X 10(5) focus-forming units (ffu) in three doses starting at 6 weeks : 4 weeks apart each dose Receives: Biological: Oral Rotavirus Vaccine 116E Live Attenuated |
What is being measured
The primary outcome is the main question the study is designed to answer.
116E rotavirus vaccine
Safety
Measured: 6,10 and 14 weeks
Secondary outcomes (1)
116E rotavirus vaccine
immunogenicity
Measured: 6,10 and 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2007 (estimated)
- Study startDec 2006
- Primary completionNov 2008
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for DiarrheaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised double blind placebo controlled tri
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 540 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bharat Biotech International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ministry of Science and Technology, India, Centers for Disease Control and Prevention, National Institutes of Health (NIH), Stanford University, Indian Council of Medical Research, PATH
- Responsible party
- Sponsor
- Investigators
- Nita Bhandari, MBBS, PhD, Principal investigator, Society for Applied Studies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00439660
- Sponsor's protocol ID
- BBIL/ROTA/014
- Other IDs
- ISRCTN57452882
- Status last verified
- Feb 2021
- First submitted
- 23 Feb 2007
- Last updated
- 23 Feb 2021
- Results posted
- No
Publications
Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, Saksena M, Rao CD, Gentsch JR, Parashar U, Maldonado Y, Ward RL, Bhan MK. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial. Vaccine. 2006 Jul 26;24(31-32):5817-23. doi: 10.1016/j.vaccine.2006.05.001. Epub 2006 May 12.
PubMed 16735085Appaiahgari MB, Glass R, Singh S, Taneja S, Rongsen-Chandola T, Bhandari N, Mishra S, Vrati S. Transplacental rotavirus IgG interferes with immune response to live oral rotavirus vaccine ORV-116E in Indian infants. Vaccine. 2014 Feb 3;32(6):651-6. doi: 10.1016/j.vaccine.2013.12.017. Epub 2013 Dec 25.
PubMed 24374502Bhandari N, Sharma P, Taneja S, Kumar T, Rongsen-Chandola T, Appaiahgari MB, Mishra A, Singh S, Vrati S; Rotavirus Vaccine Development Group. A dose-escalation safety and immunogenicity study of live attenuated oral rotavirus vaccine 116E in infants: a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2009 Aug 1;200(3):421-9. doi: 10.1086/600104.
PubMed 19545211
Study at a glance
From the registry record, last updated by the sponsor on 23 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Randomized Placebo-Controlled Dose Escalating Phase Ib/IIa Study to Evaluate the Safety and Immunogenicity of Live Attenuated Oral Rotavirus Vaccine 116E in Healthy Non-Malnourished Infants 8 to 20 Weeks of Age
- ClinicalTrials.gov ID
- NCT00439660
- Acronym / sponsor ID
- BBIL/ROTA/014
- Conditions
- Diarrhea
- Keywords
- Rotavirus, diarrhea, vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 540 participants (actual)
- Lead sponsor
- Bharat Biotech International LimitedIndustry (pharma, biotech, devices)
- Collaborators
- Ministry of Science and Technology, India, Centers for Disease Control and Prevention, National Institutes of Health (NIH), Stanford University, Indian Council of Medical Research, PATH
- Study start
- Dec 2006
- Primary completion
- Nov 2008 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 26 Feb 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be a Phase I, randomized, double blind, safety and immunogenicity trial of the Vero cell based 116E neonatal rotavirus vaccine candidate strain in healthy non-malnourished infants aged 8-20 weeks at three different dosage levels i.e.10^4.0, 10^5.0 and 10^6.0 FFU and for three administrations of each of these dosages given to infants at 4-week intervals. 180 infants (90 vaccinees/90 placebo) will be enrolled for each of the three dosage levels. The progression from the lower to the next higher dosage will be based on approval by the Data Safety Monitoring Board (DSMB) to be constituted by the Department of Biotechnology, New Delhi.
Detailed description
Infants will be identified through a community survey in urban neighborhoods in the city of Delhi, India and screened at 6 weeks of age if parental consent is available. They will be given the first dose of EPI vaccines at this age. Of those screened, eligible infants will be given the first administration of the test vaccine/placebo at 8 weeks of age if they meet the enrollment inclusion criteria, and consent is available. The safety profile will be studied through daily home visits for 14 days post administration. Stool specimens will be collected before vaccination (day 0) and on days 3, 7 and 28 post administration of vaccine/placebo. Subsequently, two contacts will be made; a home visit on day 21 and a clinic visit on day 28. On the day 28 visit, a stool and blood specimen will be collected. Prior to each administration of vaccine/placebo the infants will be assessed for any contraindications.
All screened infants will be offered EPI vaccines as scheduled. The second and third administration of study vaccine/placebo will be at 12 and 16 weeks of age and the same strategy will be followed for each of the three dosages The study vaccine/placebo are not being administered with the EPI vaccines even though in the future rotavirus vaccine and the EPI vaccines may be coadministered. For the purpose of this study this schedule is being adopted, as no data are available on the interaction of EPI vaccines with this rotavirus vaccine candidate.
Baseline sera will be collected at 6 weeks (at the time of screening) and again 4 weeks after administration of the vaccine/placebo in a randomly selected subsample after the first (60 infants), second (60 infants) and third (60 infants) administration of each dosage.
Clinical adverse events will be monitored and relatedness to vaccine/placebo administration assessed for 14 days after each administration of the dosage under study, whereas monitoring for symptoms of intussusception will be assessed throughout the 28 day follow up period. Laboratory adverse events will be monitored for upto 28 days after first administration of each dosage. After the 4 week follow up of the third administration of the vaccine/placebo of the lowest dosage (10^4.0) is completed for all enrolled infants and the data safety monitoring board (DSMB) meeting will be convened and the data from the study will be analyzed, the code broken. If the DSMB declares the dosage safe, guided by the apriori criteria, the team will move on to screening infants for the next higher dosage (10^5.0) and the strategy listed above will be repeated for a total of 180 enrolled infants (90 vaccinees/90 placebo). The DSMB will again meet to review the data available from this cohort (i.e. 10^5.0) and the team will proceed to screen infants for the next higher dosage (10^6.0) only if the former is declared safe.
At the end of the study i.e. after the last visit of the last participant, based on reactogenicity and immunogenicity profile of each dosage, the appropriate dosage will be selected for further clinical evaluation.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised double blind placebo controlled tri
| Arm | Type | Receives |
|---|---|---|
| rotavirus vaccine 116E 1 X 10(4) | Experimental | Biological: Oral Rotavirus Vaccine 116E Live Attenuatedvaccine dose of 1 X 10(4) focus-forming units (ffu) in three doses starting at 6 weeks : 4 weeks apart each dose |
| rotavirus vaccine 116E 1 X 10(5) | Experimental | Biological: Oral Rotavirus Vaccine 116E Live Attenuatedvaccine dose of 1 X 10(5) focus-forming units (ffu) in three doses starting at 6 weeks : 4 weeks apart each dose |
Who may qualify
- Ages
- 8 to 20 weeks
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Access to telephone at home or in the immediate neighborhood.
- Healthy male and female non-malnourished (weight for length not ≤ -3 SD of WHO child growth standards) infants aged 6 weeks (till 6 weeks + 2 days).
- Parent's permission to participate in the study is available.
- No plans to travel over the next 4 months
Key exclusion criteria (33 listed)
- Gestational age <37 weeks.
- Any major physical congenital malformation.
- Living in a household or has contact with an individual who is immunosuppressed.
- Hospitalized once or more for the following illnesses since birth: heart disease, pneumonia, sepsis, meningitis, unconsciousness.
- Is required to take daily medications other than vitamins or herbal "tonics".
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Rotavirus Vaccine 116E Live Attenuated | Biological | rotavirus vaccine 116E 1 X 10(4), rotavirus vaccine 116E 1 X 10(5) |
Primary outcome
116E rotavirus vaccine
Time frame: 6,10 and 14 weeks
Safety
1 secondary outcome
116E rotavirus vaccine
Time frame: 6,10 and 14 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Feb 2021.
- Background: PubMed 16735085Bhandari N, Sharma P, Glass RI, Ray P, Greenberg H, Taneja S, Saksena M, Rao CD, Gentsch JR, Parashar U, Maldonado Y, Ward RL, Bhan MK. Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial. Vaccine. 2006 Jul 26;24(31-32):5817-23. doi: 10.1016/j.vaccine.2006.05.001. Epub 2006 May 12.
- Derived from this study: PubMed 24374502Appaiahgari MB, Glass R, Singh S, Taneja S, Rongsen-Chandola T, Bhandari N, Mishra S, Vrati S. Transplacental rotavirus IgG interferes with immune response to live oral rotavirus vaccine ORV-116E in Indian infants. Vaccine. 2014 Feb 3;32(6):651-6. doi: 10.1016/j.vaccine.2013.12.017. Epub 2013 Dec 25.
- Derived from this study: PubMed 19545211Bhandari N, Sharma P, Taneja S, Kumar T, Rongsen-Chandola T, Appaiahgari MB, Mishra A, Singh S, Vrati S; Rotavirus Vaccine Development Group. A dose-escalation safety and immunogenicity study of live attenuated oral rotavirus vaccine 116E in infants: a randomized, double-blind, placebo-controlled trial. J Infect Dis. 2009 Aug 1;200(3):421-9. doi: 10.1086/600104.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nita Bhandari, MBBS, PhD principal investigator
Society for Applied Studies
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oral Rotavirus Vaccine 116E Live Attenuated in people with Diarrhea, run by Bharat Biotech International Limited at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
116E rotavirus vaccine (time frame: 6,10 and 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00439660, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2021.