Back to resultsEfficacy, Safety and Immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in Neonates
Primary Purpose
Rotavirus Gastroenteritis
Status
Active
Phase
Phase 3
Locations
Indonesia
Study Type
Interventional
Intervention
Rotavirus RV3 Vaccine (Bio Farma)
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Rotavirus Gastroenteritis focused on measuring Rotavirus, Vaccine
Eligibility Criteria
Inclusion Criteria:
- Neonate 0-5 days (0-144 hours) of age at the time of first dose.
- Neonate is in good health as determined by clinical judgment, including a medical history and physical exam, which confirms the absence of a current or past disease state considered significant by the investigator.
- The neonate was born full term (minimum of 37 completed weeks and maximum of 42 completed weeks gestation).
- Neonate birth weight 2500-4000 g inclusive.
- Parent or guardian has been informed properly regarding the study and signed the informed consent form.
- Parent or guardian commits to comply with the instructions of the investigator and the schedule of the trial.
Exclusion Criteria:
- Subject concomitantly enrolled or scheduled to be enrolled in another trial.
- The subject has direct relatives relationship with the study team.
- The subject has evolving mild, moderate or severe illness, especially infectious diseases or fever (body temperature 37.5°C) within the 48 hours preceding enrollment.
- Subject with a known or suspected history of allergy to any component of the vaccines (based on anamnesis).
- Subject with a biological mother with a known or suspected human immunodeficiency virus (HIV) or Hepatitis B infection.
- Subject with known or suspected major congenital malformations or genetically determined disease.
- Subject with intussusception.
- Subject with a known or suspected disease of uncontrolled coagulopathy or blood disorders contraindicating for phlebotomy.
- Subject with a known or suspected disease of the immune system or those who have received immunosuppressive therapy, including immunosuppressive courses of systemic corticosteroid.
- Subject who have ever received any blood products, including immunoglobulin, or for whom receipt of any blood product is anticipated during the course of study.
- Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives.
- Subject immunized with non-EPI vaccines.
- Gastroenteritis in the 24 hours preceding dosing (temporary exclusion criteria).
- Subject planning to move from the study area before the end of the study period.
Sites / Locations
- Dr. Moewardi District Hospital
- Gajahan Primary Health Center
- Gambirsari Primary Health Center
- Pajang Primary Health Center
- Sangkrah Primary Health Center
- Sibela Primary Health Center
- Bayat Primary Health Center
- dr. Soeradji Tirtonegoro General Hospital
- Gantiwarno Primary Health Center
- Jogonalan 1 Primary Health Center
- Jogonalan 2 Primary Health Center
- Karanganom Primary Health Center
- Kebonarum Primary Health Center
- Kebondalem Lor Primary Health Center
- Klaten Selatan Primary Health Center
- Ngawen Primary Health Center
- Pedan Primary Health Center
- Prambanan Primary Health Center
- Trucuk 1 Primary Health Center
- Trucuk 2 Primary Health Center
- Wedi Primary Health Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Arm Label
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 1
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 2
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 3
Immunogenicity Group - Placebo
Other Efficacy Group - RV3 Vaccine (Bio Farma)
Other Efficacy Group - Placebo
Arm Description
3 oral doses of RV3 vaccine (Bio Farma) batch 1; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
3 oral doses of RV3 vaccine (Bio Farma) batch 2; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
3 oral doses of RV3 vaccine (Bio Farma) batch 3; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
3 oral doses of Placebo; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
3 oral doses of RV3 vaccine (Bio Farma) administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
3 oral doses of Placebo administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Outcomes
Primary Outcome Measures
Efficacy of three doses against severe acute rotavirus gastroenteritis
Episodes of severe rotavirus gastroenteritis (defined as a modified Vesikari score ≥ 11 and rotavirus antigen detected in stool by ELISA)
Secondary Outcome Measures
Efficacy of three doses against rotavirus gastroenteritis of any severity and all-cause gastroenteritis
Episodes of rotavirus gastroenteritis of any severity (based on modified Vesikari score and rotavirus antigen detected in stool by ELISA) and all-cause gastroenteritis
Serum immune response (sIgA) after third dose
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the third dose
Stool excretion following each dose
Detectable RV3 excretion in stool (by PCR) any day from day 3 to day 5 following each dose
Cumulative serum immune response
Cumulative serum anti-rotavirus IgA (sIgA) following each dose
Lot to lot consistency
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the third dose
Solicited and unsolicited adverse events (AE)
Number of solicited and unsolicited Adverse Events (AE), from randomization to 28 days following last dose
Serious adverse events (SAE)
Number of Serious Adverse Events (SAE), from randomization to 28 days following last dose
Serum immune response (sIgA) after the first dose
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the first dose
Serum immune response (sIgA) after the second dose
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the second dose
Abnormality of ALT and AST levels
Abnormality of ALT and AST levels measured 28 days following first dose, assessed as probably or definitely related to the dosing
Immune interference
Percentage of subjects with reciprocal titre ≥ 1:8 against poliovirus strains 1-3 measured 28 days after bOPV4+ IPV and Pentabio 3 vaccination
Geometric Mean Titre (GMT)
Geometric Mean Titre (GMT) of serum IgA 28 days after each dose
Serum neutralizing antibodies (SNA) after the third dose
Percentage of subjects with positive SNA (≥ 100), two-fold and three-fold increasing antibodies from baseline to 28 days after the third dose
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04185545
Brief Title
Efficacy, Safety and Immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in Neonates
Official Title
Efficacy, Safety and Immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in Neonates, Lot to Lot Consistency and Antigen Interference With Co-Administered EPI Vaccines (Phase III)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 30, 2020 (Actual)
Primary Completion Date
April 30, 2022 (Actual)
Study Completion Date
May 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PT Bio Farma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This phase III trial aims to assess the efficacy, safety and immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in neonates, lot-to-lot consistency, and antigen interference with co-administered EPI vaccines
Detailed Description
This study is a randomized, double-blind, placebo-controlled study to investigate the efficacy, safety and immunogenicity following three doses of rotavirus RV3 vaccine (Bio Farma) administered as a neonatal schedule
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rotavirus Gastroenteritis
Keywords
Rotavirus, Vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
1400 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 1
Arm Type
Experimental
Arm Description
3 oral doses of RV3 vaccine (Bio Farma) batch 1; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Arm Title
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 2
Arm Type
Experimental
Arm Description
3 oral doses of RV3 vaccine (Bio Farma) batch 2; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Arm Title
Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 3
Arm Type
Experimental
Arm Description
3 oral doses of RV3 vaccine (Bio Farma) batch 3; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Arm Title
Immunogenicity Group - Placebo
Arm Type
Placebo Comparator
Arm Description
3 oral doses of Placebo; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Arm Title
Other Efficacy Group - RV3 Vaccine (Bio Farma)
Arm Type
Experimental
Arm Description
3 oral doses of RV3 vaccine (Bio Farma) administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Arm Title
Other Efficacy Group - Placebo
Arm Type
Placebo Comparator
Arm Description
3 oral doses of Placebo administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age.
Intervention Type
Biological
Intervention Name(s)
Rotavirus RV3 Vaccine (Bio Farma)
Intervention Description
Each 1 mL dose of the final product of oral liquid rotavirus vaccine contains > 5x10^6 fcfu/mL rotavirus vaccine strain RV3
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Each 1 mL dose of placebo contains 30% of sucrose in DMEM
Primary Outcome Measure Information:
Title
Efficacy of three doses against severe acute rotavirus gastroenteritis
Description
Episodes of severe rotavirus gastroenteritis (defined as a modified Vesikari score ≥ 11 and rotavirus antigen detected in stool by ELISA)
Time Frame
2 weeks after three doses to 18 months of age
Secondary Outcome Measure Information:
Title
Efficacy of three doses against rotavirus gastroenteritis of any severity and all-cause gastroenteritis
Description
Episodes of rotavirus gastroenteritis of any severity (based on modified Vesikari score and rotavirus antigen detected in stool by ELISA) and all-cause gastroenteritis
Time Frame
2 weeks after three doses to 18 months of age
Title
Serum immune response (sIgA) after third dose
Description
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the third dose
Time Frame
28 days after the third dose
Title
Stool excretion following each dose
Description
Detectable RV3 excretion in stool (by PCR) any day from day 3 to day 5 following each dose
Time Frame
3-5 days after each dose
Title
Cumulative serum immune response
Description
Cumulative serum anti-rotavirus IgA (sIgA) following each dose
Time Frame
28 days after each dose
Title
Lot to lot consistency
Description
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the third dose
Time Frame
28 days after the third dose
Title
Solicited and unsolicited adverse events (AE)
Description
Number of solicited and unsolicited Adverse Events (AE), from randomization to 28 days following last dose
Time Frame
Up to 28 days after the third dose
Title
Serious adverse events (SAE)
Description
Number of Serious Adverse Events (SAE), from randomization to 28 days following last dose
Time Frame
Up to 28 days after the third dose
Title
Serum immune response (sIgA) after the first dose
Description
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the first dose
Time Frame
28 days after the first dose
Title
Serum immune response (sIgA) after the second dose
Description
Percentage of subjects with ≥ 3 times increase in serum anti-rotavirus IgA (sIgA) from baseline to 28 days after the second dose
Time Frame
28 days after the second dose
Title
Abnormality of ALT and AST levels
Description
Abnormality of ALT and AST levels measured 28 days following first dose, assessed as probably or definitely related to the dosing
Time Frame
28 days after the first dose
Title
Immune interference
Description
Percentage of subjects with reciprocal titre ≥ 1:8 against poliovirus strains 1-3 measured 28 days after bOPV4+ IPV and Pentabio 3 vaccination
Time Frame
28 days after non-EPI vaccination
Title
Geometric Mean Titre (GMT)
Description
Geometric Mean Titre (GMT) of serum IgA 28 days after each dose
Time Frame
28 days after each dose
Title
Serum neutralizing antibodies (SNA) after the third dose
Description
Percentage of subjects with positive SNA (≥ 100), two-fold and three-fold increasing antibodies from baseline to 28 days after the third dose
Time Frame
28 days after the third dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Minute
Maximum Age & Unit of Time
5 Days
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Neonate 0-5 days (0-144 hours) of age at the time of first dose.
Neonate is in good health as determined by clinical judgment, including a medical history and physical exam, which confirms the absence of a current or past disease state considered significant by the investigator.
The neonate was born full term (minimum of 37 completed weeks and maximum of 42 completed weeks gestation).
Neonate birth weight 2500-4000 g inclusive.
Parent or guardian has been informed properly regarding the study and signed the informed consent form.
Parent or guardian commits to comply with the instructions of the investigator and the schedule of the trial.
Exclusion Criteria:
Subject concomitantly enrolled or scheduled to be enrolled in another trial.
The subject has direct relatives relationship with the study team.
The subject has evolving mild, moderate or severe illness, especially infectious diseases or fever (body temperature 37.5°C) within the 48 hours preceding enrollment.
Subject with a known or suspected history of allergy to any component of the vaccines (based on anamnesis).
Subject with a biological mother with a known or suspected human immunodeficiency virus (HIV) or Hepatitis B infection.
Subject with known or suspected major congenital malformations or genetically determined disease.
Subject with intussusception.
Subject with a known or suspected disease of uncontrolled coagulopathy or blood disorders contraindicating for phlebotomy.
Subject with a known or suspected disease of the immune system or those who have received immunosuppressive therapy, including immunosuppressive courses of systemic corticosteroid.
Subject who have ever received any blood products, including immunoglobulin, or for whom receipt of any blood product is anticipated during the course of study.
Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives.
Subject immunized with non-EPI vaccines.
Gastroenteritis in the 24 hours preceding dosing (temporary exclusion criteria).
Subject planning to move from the study area before the end of the study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Titis Widowati
Organizational Affiliation
Center for Child Health Universitas Gadjah Mada (CCH-PRO UGM
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hari Wahyu N.
Organizational Affiliation
Pediatric Research Center Universitas Sebelas Maret (PRC UNS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dr. Moewardi District Hospital
City
Surakarta
Country
Indonesia
Facility Name
Gajahan Primary Health Center
City
Surakarta
Country
Indonesia
Facility Name
Gambirsari Primary Health Center
City
Surakarta
Country
Indonesia
Facility Name
Pajang Primary Health Center
City
Surakarta
Country
Indonesia
Facility Name
Sangkrah Primary Health Center
City
Surakarta
Country
Indonesia
Facility Name
Sibela Primary Health Center
City
Surakarta
Country
Indonesia
Facility Name
Bayat Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
dr. Soeradji Tirtonegoro General Hospital
City
Yogyakarta
Country
Indonesia
Facility Name
Gantiwarno Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Jogonalan 1 Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Jogonalan 2 Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Karanganom Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Kebonarum Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Kebondalem Lor Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Klaten Selatan Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Ngawen Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Pedan Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Prambanan Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Trucuk 1 Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Trucuk 2 Primary Health Center
City
Yogyakarta
Country
Indonesia
Facility Name
Wedi Primary Health Center
City
Yogyakarta
Country
Indonesia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Efficacy, Safety and Immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in Neonates
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