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

Rotavirus Gastroenteritis Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04185545
• Other study ID #: RV 0319
• Status: Completed
• Phase: Phase 3
• Start date: October 30, 2020
• Est. completion date: May 30, 2023

Study information

• Verified date: November 2023
• Source: PT Bio Farma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1400
• Est. completion date: May 30, 2023
• Est. primary completion date: April 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Minute to 5 Days

Eligibility

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.

Related Conditions & MeSH terms

• Gastroenteritis
• Rotavirus Gastroenteritis

Intervention

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

Other:
• Placebo
Each 1 mL dose of placebo contains 30% of sucrose in DMEM

Locations

Country	Name	City	State
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	Surakarta
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	Yogyakarta

Sponsors (1)

Lead Sponsor	Collaborator
PT Bio Farma

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Cumulative serum immune response	Cumulative serum anti-rotavirus IgA (sIgA) following each dose	28 days after each dose
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Geometric Mean Titre (GMT)	Geometric Mean Titre (GMT) of serum IgA 28 days after each dose	28 days after each dose
Secondary	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