Efficacy, Safety and Immunogenicity of Rotavirus RV3 Vaccine (Bio Farma) in Neonates

Study Overview
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Brief Summary
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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
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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

Official Title
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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)

Conditions
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Rotavirus Gastroenteritis

Intervention / Treatment
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* Biological: Rotavirus RV3 Vaccine (Bio Farma)
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 5 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 1<br>3 oral doses of RV3 vaccine (Bio Farma) batch 1; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Biological: Rotavirus RV3 Vaccine (Bio Farma)<br>* Each 1 mL dose of the final product of oral liquid rotavirus vaccine contains > 5x10^6 fcfu/mL rotavirus vaccine strain RV3<br>|
| Experimental: Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 2<br>3 oral doses of RV3 vaccine (Bio Farma) batch 2; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Biological: Rotavirus RV3 Vaccine (Bio Farma)<br>* Each 1 mL dose of the final product of oral liquid rotavirus vaccine contains > 5x10^6 fcfu/mL rotavirus vaccine strain RV3<br>|
| Experimental: Immunogenicity Group - RV3 Vaccine (Bio Farma) Batch 3<br>3 oral doses of RV3 vaccine (Bio Farma) batch 3; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Biological: Rotavirus RV3 Vaccine (Bio Farma)<br>* Each 1 mL dose of the final product of oral liquid rotavirus vaccine contains > 5x10^6 fcfu/mL rotavirus vaccine strain RV3<br>|
| Placebo Comparator: Immunogenicity Group - Placebo<br>3 oral doses of Placebo; administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Other: Placebo<br>* Each 1 mL dose of placebo contains 30% of sucrose in DMEM<br>|
| Experimental: Other Efficacy Group - RV3 Vaccine (Bio Farma)<br>3 oral doses of RV3 vaccine (Bio Farma) administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Biological: Rotavirus RV3 Vaccine (Bio Farma)<br>* Each 1 mL dose of the final product of oral liquid rotavirus vaccine contains > 5x10^6 fcfu/mL rotavirus vaccine strain RV3<br>|
| Placebo Comparator: Other Efficacy Group - Placebo<br>3 oral doses of Placebo administered at 0-5 days, 8-10 weeks, and 12-14 weeks of age. | Other: Placebo<br>* Each 1 mL dose of placebo contains 30% of sucrose in DMEM<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 2 weeks after three doses to 18 months of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 weeks after three doses to 18 months of age | 
| 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 | 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 | 3-5 days after each dose | 
| Cumulative serum immune response | Cumulative serum anti-rotavirus IgA (sIgA) following each dose | 28 days after 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 | 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 | Up to 28 days after the third dose | 
| Serious adverse events (SAE) | Number of Serious Adverse Events (SAE), from randomization to 28 days following last dose | Up to 28 days after the third 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 | 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 | 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 | 28 days after the first dose | 
| 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 | 28 days after non-EPI vaccination | 
| Geometric Mean Titre (GMT) | Geometric Mean Titre (GMT) of serum IgA 28 days after each dose | 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 | 28 days after the third dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rotavirus, Vaccine