DiarrheaPhase 3NCT03703336
Phase III Study of Liquid Formulation of ROTAVIN
A Phase 3 study testing ROTAVIN (liquid formulation) and ROTAVIN-M1 (frozen formulation) in people with Diarrhea and Diarrhea Rotavirus, run by Center for Research and Production of Vaccines and Biologicals, Vietnam at 2 sites in Vietnam.
Trial summary
This study is conducted to demonstrate non-inferiority in the immunogenicity of the liquid formulation of ROTAVIN in comparison to currently licensed frozen formulation of the vaccine (ROTAVIN-M1), 28 days after the second vaccination when administered as two dose series starting at 2-3 months of age. Read more about this study
- Who is it for?
- Ages 60 to 91 daysHealthy volunteers can take part
- Conditions the study is for
- Diarrhea, Diarrhea Rotavirus
- What is being tested?
- ROTAVIN (liquid formulation) and ROTAVIN-M1 (frozen formulation)
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 825 participants
- Where
- 2 sitesVietnam
- Study dates
- 16 Mar 2019to 8 Jan 2020
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 to 91 days
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Healthy infants as established by medical history and clinical examination before entering the study.
- Age: 60-91 days (both days inclusive) at the time of enrollment.
- Parental/legally acceptable representative ability and willingness to provide written informed consent.
- Parent/legally acceptable representative who intends to remain in the area with the child during the study period.
Who cannot join
- Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion).
- Presence of fever on the day of enrollment (temporary exclusion).
- Acute disease at the time of enrollment (temporary exclusion).
- Concurrent participation in another clinical trial at any point throughout the entire time frame for this study.
- Presence of significant malnutrition (weight-for-height z-score < -3 SD median)
- Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer, or autoimmune disease) as determined by medical history and / or physical examination which would compromise the participant's health or is likely to result in nonconformance to the protocol.
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- History of congenital abdominal disorders, intussusception, or abdominal surgery.
- Known or suspected impairment of immunological function based on medical history and physical examination.
- Household contact with an immunosuppressed individual or pregnant woman.
- Prior receipt of rotavirus or an intent to receive this vaccine from outside of the study center during study participation.
- Prior receipt of Expanded Program on Immunization (EPI) vaccination during past 7 days or plan to receive them within next 7 days.
- A known sensitivity or allergy to any components of the study vaccine.
- History of allergy to antibiotic kanamycin.
- Clinically detectable significant congenital or genetic defect.
- History of persistent diarrhea (defined as diarrhea that lasts 14 days or longer).
- Receipt of immunoglobulin therapy and / or blood products since birth or planned administration during the study period.
- History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study.
- Any medical condition in the parent/legally acceptable representative or infant which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence.
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Phase III, Randomized, Partially Double- Blind, Active Control Study to Compare the Immunogenicity and Safety of a Liquid Formulation of ROTAVIN With the Currently Licensed Frozen Formulation of the Vaccine (ROTAVIN-M1), in Healthy Vietnamese Infants
This study is conducted to demonstrate non-inferiority in the immunogenicity of the liquid formulation of ROTAVIN in comparison to currently licensed frozen formulation of the vaccine (ROTAVIN-M1), 28 days after the second vaccination when administered as two dose series starting at 2-3 months of age.
The study will also assess the reactogenicity of the vaccine 7 days after each vaccination and safety from first vaccination up to 4 weeks after the last vaccination.
Read the detailed description
The study is designed as a phase III, randomized, partially double-blinded, active controlled study with two groups of infants receiving vaccines at the ratio of 2:1 (liquid formulation of ROTAVIN to frozen formulation ROTAVIN-M1), to compare their immunogenicity and safety. Two doses of vaccine will be administered 8 weeks apart with the first vaccine administration between 60-91 days of age. All childhood vaccines as per the Expanded Program for Immunization of the Government of Vietnam (including Diphtheria, Tetanus, Pertussis, Haemophilus influenzae type b and Hepatitis B vaccine (DTwPHib-HepB), and Oral Polio Vaccine at at 2, 3 and 4 months of age) will be allowed as per the immunization schedule.
Active surveillance for vaccine reactogenicity (solicited reactions) over the 7-day period after each vaccination, unsolicited adverse events (AEs) for 4 weeks after each vaccination and serious adverse events (SAEs) including intussusception over the period between first vaccination and four weeks after the last vaccination will be conducted for all infants.
This trial will generate immunogenicity and safety data which would be submitted to Ministry of Health in Vietnam for license of new formulation of ROTAVIN vaccine.
- Conditions
- Diarrhea, Diarrhea Rotavirus
- Being tested
- ROTAVIN (liquid formulation), ROTAVIN-M1 (frozen formulation)
- Keywords
- ROTAVIN, Rotavirus vaccine, Rotavirus, Diarrhea
- Medical subject headings
- Diarrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ROTAVIN (liquid formulation)Biological
Live attenuated human rotavirus vaccine containing ≥ 2x10^6 plaque forming units (PFU) of strain G1P[8] per dose of 2 mL.
ROTAVIN-M1 (frozen formulation)Biological
Live attenuated human rotavirus vaccine containing ≥ 2x10^6 PFU of strain G1P[8] per dose of 2 mL.
| Study group | Role | What they receive |
|---|---|---|
| ROTAVIN Liquid Formulation | Experimental | Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age. Receives: Biological: ROTAVIN (liquid formulation) |
| ROTAVIN-M1 Frozen Formulation | Active comparator | Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age. Receives: Biological: ROTAVIN-M1 (frozen formulation) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination
Serum anti-rotavirus IgA antibodies were measured using a validated enzyme linked immunosorbent assay (ELISA) at the Cincinnati Children's Hospital Medical Center (CCHMC), Division of Infectious Diseases in Cincinnati, Ohio USA.
Measured: Day 85 (28 days after the second vaccination)
Number of Participants With Solicited Reactions Within 7 Days of Vaccination
Solicited post-vaccination reactogenicity included fever, diarrhea, vomiting, decreased appetite, irritability, and decreased activity level during the seven-day period after each vaccination. Parents were asked to record reactions on a post-immunization diary card.
Solicited reactions were graded for severity on a scale from mild to severe based on the level of symptoms.
Measured: 7 days after each vaccination (Days 1 to 8 and 57 to 64)
Secondary outcomes (5)
Percentage of Participants With Seroconversion 28 Days After the Second Vaccination
Seroconversion is defined as a post-vaccination serum anti-rotavirus IgA antibody concentration of at least 20 U/mL if the baseline concentration was < 20 U/mL or a post- vaccination serum anti-rotavirus IgA antibody concentration of ≥ 4-fold baseline level if the baseline concentration was ≥ 20 U/mL.
Measured: 28 days after the second vaccination (Day 85)
Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination
Seropositivity is defined as serum IgA antibody concentration ≥ 20 U/mL
Measured: Baseline (Day 1) and at 28 days after the second vaccination (Day 85)
Number of Participants With Immediate Adverse Events (AEs)
After each vaccination participants were observed at the clinic site for at least 30 minutes to check for any immediate AEs including episodes of vomiting and allergic reaction to vaccine. Immediate AEs include all reactions that occurred within 30 minutes of each vaccination.
Reactions were graded for severity per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 2.1, of the US National Institute of Health:
Grade 1: Mild symptoms causing no or minimal interference with usual social \& functional activities; intervention not indicated.
Grade 2: Moderate symptoms causing greater than minimal interference with usual activities; intervention indicated.
Grade 3: Severe symptoms causing inability to perform usual activities; intervention or hospitalization indicated.
Grade 4: Potentially life-threatening symptoms; intervention indicated to prevent permanent impairment, persistent disability, or death
Grade 5: Death
Measured: Within 30 minutes after each vaccination on Day 1 and Day 57
Number of Participants With Unsolicited Adverse Events
An unsolicited AE was any AE that occurred after vaccination, whether or not deemed "related" to the product, that was not solicited, or, any solicited reaction that started after 7 days post-vaccination. Severity of unsolicited AEs was graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, version 2.1.
Grade 1: Mild symptoms causing no or minimal interference with usual social \& functional activities; intervention not indicated
Grade 2: Moderate symptoms causing greater than minimal interference with usual activities; intervention indicated
Grade 3: Severe symptoms causing inability to perform usual activities; intervention or hospitalization indicated
Grade 4: Potentially life-threatening symptoms; intervention indicated to prevent permanent impairment, persistent disability, or death
Grade 5: Death
The clinician classified the causality of each AE as related if there was reasonable possibility that the product caused the event.
Measured: From vaccination through 28 days after each dose (Days 1 to 28 and 57 to 85)
Number of Participants With Serious Adverse Events Including Intussusception
All Serious adverse events (SAEs), including cases of intussusception, were recorded at all time points between first vaccination and last visit. An SAE was defined as any untoward medical occurrence that:
- Resulted in death,
- Was life threatening,
- Required inpatient hospitalization or prolongation of existing hospitalization,
- Resulted in persistent or significant disability / incapacity,
- Was a congenital anomaly or a birth defect,
- Medically important event
Investigator-confirmed cases of intussusception also qualified as an SAE in this study. Intussusception is the infolding (telescoping) of one segment of the intestine within another, usually resulting in a blockage of the intestine.
Measured: From first vaccination through 28 days after the last vaccination; 85 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2018
- Study start16 Mar 2019
- Primary completion8 Jan 2020
- Study completion8 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible infants will be randomized to receive either ROTAVIN or ROTAVIN-M1 vaccines in the ratio of 2:1.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 825 participants (actual)
Sponsor and investigators
- Lead sponsor
- Center for Research and Production of Vaccines and Biologicals, Vietnam
- Sponsor type
- Other government
- Collaborators
- PATH, National Institute of Hygiene and Epidemiology, Vietnam, Children's Hospital Medical Center, Cincinnati
- Responsible party
- Sponsor
- Investigators
- Niraj Rathi, MD, Study director, PATH India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03703336
- Sponsor's protocol ID
- CVIA 068
- Other IDs
- VX.2018.05
- Status last verified
- Nov 2020
- First submitted
- 9 Oct 2018
- Last updated
- 25 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Thiem VD, Anh DD, Ha VH, Hien ND, Huong NT, Nga NT, Thang TC, McNeal MM, Meyer N, Pham HL, Huong NM, Gompana G, Cassels F, Tang Y, Flores J, Rathi N. Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants. Vaccine. 2021 Jul 22;39(32):4463-4470. doi: 10.1016/j.vaccine.2021.06.056. Epub 2021 Jul 1.
PubMed 34218961
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Randomized, Partially Double- Blind, Active Control Study to Compare the Immunogenicity and Safety of a Liquid Formulation of ROTAVIN With the Currently Licensed Frozen Formulation of the Vaccine (ROTAVIN-M1), in Healthy Vietnamese Infants
- ClinicalTrials.gov ID
- NCT03703336
- Acronym / sponsor ID
- CVIA 068
- Conditions
- Diarrhea, Diarrhea Rotavirus
- Keywords
- ROTAVIN, Rotavirus vaccine, Rotavirus, Diarrhea
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 825 participants (actual)
- Lead sponsor
- Center for Research and Production of Vaccines and Biologicals, VietnamOther government
- Collaborators
- PATH, National Institute of Hygiene and Epidemiology, Vietnam, Children's Hospital Medical Center, Cincinnati
- Study start
- 16 Mar 2019 (actual)
- Primary completion
- 8 Jan 2020 (actual)
- Study completion
- 8 Jan 2020 (actual)
- First posted
- 11 Oct 2018 (actual)
- Results
- Posted 25 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is conducted to demonstrate non-inferiority in the immunogenicity of the liquid formulation of ROTAVIN in comparison to currently licensed frozen formulation of the vaccine (ROTAVIN-M1), 28 days after the second vaccination when administered as two dose series starting at 2-3 months of age.
The study will also assess the reactogenicity of the vaccine 7 days after each vaccination and safety from first vaccination up to 4 weeks after the last vaccination.
Detailed description
The study is designed as a phase III, randomized, partially double-blinded, active controlled study with two groups of infants receiving vaccines at the ratio of 2:1 (liquid formulation of ROTAVIN to frozen formulation ROTAVIN-M1), to compare their immunogenicity and safety. Two doses of vaccine will be administered 8 weeks apart with the first vaccine administration between 60-91 days of age. All childhood vaccines as per the Expanded Program for Immunization of the Government of Vietnam (including Diphtheria, Tetanus, Pertussis, Haemophilus influenzae type b and Hepatitis B vaccine (DTwPHib-HepB), and Oral Polio Vaccine at at 2, 3 and 4 months of age) will be allowed as per the immunization schedule.
Active surveillance for vaccine reactogenicity (solicited reactions) over the 7-day period after each vaccination, unsolicited adverse events (AEs) for 4 weeks after each vaccination and serious adverse events (SAEs) including intussusception over the period between first vaccination and four weeks after the last vaccination will be conducted for all infants.
This trial will generate immunogenicity and safety data which would be submitted to Ministry of Health in Vietnam for license of new formulation of ROTAVIN vaccine.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Eligible infants will be randomized to receive either ROTAVIN or ROTAVIN-M1 vaccines in the ratio of 2:1.
| Arm | Type | Receives |
|---|---|---|
| ROTAVIN Liquid Formulation | Experimental | Biological: ROTAVIN (liquid formulation)Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age. |
| ROTAVIN-M1 Frozen Formulation | Active comparator | Biological: ROTAVIN-M1 (frozen formulation)Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age. |
Who may qualify
- Ages
- 60 to 91 days
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Healthy infants as established by medical history and clinical examination before entering the study.
- Age: 60-91 days (both days inclusive) at the time of enrollment.
- Parental/legally acceptable representative ability and willingness to provide written informed consent.
- Parent/legally acceptable representative who intends to remain in the area with the child during the study period.
Key exclusion criteria (18 listed)
- Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion).
- Presence of fever on the day of enrollment (temporary exclusion).
- Acute disease at the time of enrollment (temporary exclusion).
- Concurrent participation in another clinical trial at any point throughout the entire time frame for this study.
- Presence of significant malnutrition (weight-for-height z-score < -3 SD median)
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 |
|---|---|---|
| ROTAVIN (liquid formulation)Live attenuated human rotavirus vaccine containing ≥ 2x10^6 plaque forming units (PFU) of strain G1P[8] per dose of 2 mL. | Biological | ROTAVIN Liquid Formulation |
| ROTAVIN-M1 (frozen formulation)Live attenuated human rotavirus vaccine containing ≥ 2x10^6 PFU of strain G1P[8] per dose of 2 mL. | Biological | ROTAVIN-M1 Frozen Formulation |
Primary outcome
Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination
Time frame: Day 85 (28 days after the second vaccination)
Serum anti-rotavirus IgA antibodies were measured using a validated enzyme linked immunosorbent assay (ELISA) at the Cincinnati Children's Hospital Medical Center (CCHMC), Division of Infectious Diseases in Cincinnati, Ohio USA.
Number of Participants With Solicited Reactions Within 7 Days of Vaccination
Time frame: 7 days after each vaccination (Days 1 to 8 and 57 to 64)
Solicited post-vaccination reactogenicity included fever, diarrhea, vomiting, decreased appetite, irritability, and decreased activity level during the seven-day period after each vaccination. Parents were asked to record reactions on a post-immunization diary card. Solicited reactions were graded for severity on a scale from mild to severe based on the level of symptoms.
5 secondary outcomes
Percentage of Participants With Seroconversion 28 Days After the Second Vaccination
Time frame: 28 days after the second vaccination (Day 85)
Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination
Time frame: Baseline (Day 1) and at 28 days after the second vaccination (Day 85)
Number of Participants With Immediate Adverse Events (AEs)
Time frame: Within 30 minutes after each vaccination on Day 1 and Day 57
Number of Participants With Unsolicited Adverse Events
Time frame: From vaccination through 28 days after each dose (Days 1 to 28 and 57 to 85)
Number of Participants With Serious Adverse Events Including Intussusception
Time frame: From first vaccination through 28 days after the last vaccination; 85 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34218961Thiem VD, Anh DD, Ha VH, Hien ND, Huong NT, Nga NT, Thang TC, McNeal MM, Meyer N, Pham HL, Huong NM, Gompana G, Cassels F, Tang Y, Flores J, Rathi N. Safety and immunogenicity of two formulations of rotavirus vaccine in Vietnamese infants. Vaccine. 2021 Jul 22;39(32):4463-4470. doi: 10.1016/j.vaccine.2021.06.056. Epub 2021 Jul 1.
- Individual participant dataSharing planned: Undecided
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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.
Niraj Rathi, MD study director
PATH India
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing ROTAVIN (liquid formulation) and ROTAVIN-M1 (frozen formulation) in people with Diarrhea and Diarrhea Rotavirus, run by Center for Research and Production of Vaccines and Biologicals, Vietnam at 2 sites in Vietnam.
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 18 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 25 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Vietnam. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination (time frame: Day 85 (28 days after the second vaccination)). The study lists 2 primary outcomes in all. 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 NCT03703336, which also lists 1 linked publication.
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 25 Jan 2021.