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

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)

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

Study Overview

• Status: Completed
• Conditions: Rotavirus Gastroenteritis
• Intervention / Treatment: Biological: Rotavirus RV3 Vaccine (Bio Farma); Other: Placebo

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

• Study Type: Interventional
• Enrollment (Actual): 1400
• Phase: Phase 3

Contacts and Locations

Study Locations

• Indonesia
  • Surakarta, Indonesia
    • Dr. Moewardi District Hospital
  • Surakarta, Indonesia
    • Gajahan Primary Health Center
  • Surakarta, Indonesia
    • Gambirsari Primary Health Center
  • Surakarta, Indonesia
    • Pajang Primary Health Center
  • Surakarta, Indonesia
    • Sangkrah Primary Health Center
  • Surakarta, Indonesia
    • Sibela Primary Health Center
  • Yogyakarta, Indonesia
    • Bayat Primary Health Center
  • Yogyakarta, Indonesia
    • dr. Soeradji Tirtonegoro General Hospital
  • Yogyakarta, Indonesia
    • Gantiwarno Primary Health Center
  • Yogyakarta, Indonesia
    • Jogonalan 1 Primary Health Center
  • Yogyakarta, Indonesia
    • Jogonalan 2 Primary Health Center
  • Yogyakarta, Indonesia
    • Karanganom Primary Health Center
  • Yogyakarta, Indonesia
    • Kebonarum Primary Health Center
  • Yogyakarta, Indonesia
    • Kebondalem Lor Primary Health Center
  • Yogyakarta, Indonesia
    • Klaten Selatan Primary Health Center
  • Yogyakarta, Indonesia
    • Ngawen Primary Health Center
  • Yogyakarta, Indonesia
    • Pedan Primary Health Center
  • Yogyakarta, Indonesia
    • Prambanan Primary Health Center
  • Yogyakarta, Indonesia
    • Trucuk 1 Primary Health Center
  • Yogyakarta, Indonesia
    • Trucuk 2 Primary Health Center
  • Yogyakarta, Indonesia
    • Wedi Primary Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 minute to 5 days (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Neonate 0-5 days (0-144 hours) of age at the time of first dose.
2. 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.
3. The neonate was born full term (minimum of 37 completed weeks and maximum of 42 completed weeks gestation).
4. Neonate birth weight 2500-4000 g inclusive.
5. Parent or guardian has been informed properly regarding the study and signed the informed consent form.
6. Parent or guardian commits to comply with the instructions of the investigator and the schedule of the trial.

Exclusion Criteria:

1. Subject concomitantly enrolled or scheduled to be enrolled in another trial.
2. The subject has direct relatives relationship with the study team.
3. 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.
4. Subject with a known or suspected history of allergy to any component of the vaccines (based on anamnesis).
5. Subject with a biological mother with a known or suspected human immunodeficiency virus (HIV) or Hepatitis B infection.
6. Subject with known or suspected major congenital malformations or genetically determined disease.
7. Subject with intussusception.
8. Subject with a known or suspected disease of uncontrolled coagulopathy or blood disorders contraindicating for phlebotomy.
9. Subject with a known or suspected disease of the immune system or those who have received immunosuppressive therapy, including immunosuppressive courses of systemic corticosteroid.
10. 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.
11. Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives.
12. Subject immunized with non-EPI vaccines.
13. Gastroenteritis in the 24 hours preceding dosing (temporary exclusion criteria).
14. Subject planning to move from the study area before the end of the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: PT Bio Farma
• Investigators: Principal Investigator: Titis Widowati, Center for Child Health Universitas Gadjah Mada (CCH-PRO UGM; Principal Investigator: Hari Wahyu N., Pediatric Research Center Universitas Sebelas Maret (PRC UNS)

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2020
• Primary Completion (Actual): April 30, 2022
• Study Completion (Actual): May 30, 2023

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: December 2, 2019
• First Posted (Actual): December 4, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Vaccine; Rotavirus
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: RV 0319

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No