Phase I/II, Open Label, Randomized, Safety and Immunogenicity Following DTwP-Hepatitis B-Hib-IPV Vaccine (Bio Farma) in Indonesian Infants

This trial is open label, comparative, randomized, phase I/II study, experimental, randomized, open-label, three arm parallel group study. The primary objective for phase I is to evaluate the safety of the DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine within 7 days after each dose. The primary objective for phase II is to evaluate protectivity of DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine.

Study Overview

• Status: Not yet recruiting
• Conditions: Vaccine Adverse Reaction; Vaccine Reaction
• Intervention / Treatment: Biological: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula A; Biological: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula B; Biological: Registered DTwP-Hepatitis B-Hib Vaccine and IPV (Sinovac)®

Detailed Description

This trial is open label, comparative, randomized, phase I/II study. For phase I, approximately 75 subjects will be recruited and will seamlessly continue to phase II recruiting 390 subject, in total 465 subjects.

In this study, DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine will be compared to an active control (Registered DTwP-Hepatitis B-Hib Vaccine and Registered Inactivated Polio Vaccine). There are 2 formulas of DTwP-Hepatitis B-Hib-IPV Vaccine which will be used in the study. The regimen of the vaccine is 0,5 ml injected three-dose regimen with 28 days interval between doses. On the other hand, the control group will receive 0,5 ml of Registered DTwP-Hepatitis B-Hib vaccine and 0,5 ml Inactivated Bio Farma vaccine injected in three-dose regimen with 28 days interval between doses.

The safety and immunogenicity result of the Phase I study will determine the continuation of the next phase clinical trial. Clinical trial of phase II can be conducted after safety observation within 28 days after the third dose in phase I. Three hundred and ninety (390) healthy subjects aged 6-11 weeks of age will be recruited in Phase II trial.

• Study Type: Interventional
• Enrollment (Estimated): 465
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Rini Mulia Sari, MD; Phone Number: 14102 +622033755; Email: rini.mulia@biofarma.co.id
• Study Contact Backup: Name: Mita Puspita, MD; Phone Number: 5045 +622033755; Email: mita.puspita@biofarma.co.id

Study Locations

• Indonesia
  • West Java
    • Bandung, West Java, Indonesia
      • Garuda Primary Health Centre
    • Bandung, West Java, Indonesia
      • Puter Primary Health Centre
    • Bandung, West Java, Indonesia
      • Ibrahim Adjie Priamry Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Infant 6-11 weeks of age.
2. Infant born after 37-42 weeks of pregnancy.
3. Infant weighing more than 2.5 kg at birth.
4. Father or mother, or legally acceptable representative properly informed about the study and signed the informed consent form.
5. Parents will commit themselves to comply with the indications of the investigators and with the schedule of the trial.

Exclusion Criteria:

1. Child concomitantly enrolled or scheduled to be enrolled in another trial.
2. Evolving moderate or severe illness, especially infectious diseases or fever (axillary temperature ≥37.5°C on Day 0).
3. Known history of allergy to any component of the vaccines.
4. History of uncontrolled coagulopathy or blood disorders contraindicating intramuscular injection.
5. Known history of congenital or acquired immunodeficiency (including HIV infection).
6. Child who has received in the previous 4 weeks of a treatment likely to alter the immune response (intravenous immunoglobulins, blood-derived products or long term corticotherapy (> 2 weeks).
7. Other vaccination within the 7 days prior to inclusion with the exception of BCG and poliomyelitis.
8. Any abnormality or chronic disease which according to the investigator might interfere with the assessment of the trial objectives.
9. Infant with a known history of diphtheria, tetanus, pertussis, Hib, hepatitis B infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula A; 0,5 ml of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula A injected three-dose regimen with 28 days interval between doses	Biological: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula A; 0,5 ml DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula A injected three-dose regimen with 28 days interval between doses. Vaccine is injected intramuscularly in left anterolateral thigh.
Experimental: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula B; 0,5 ml of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula B injected three-dose regimen with 28 days interval between doses.	Biological: DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula B; 0,5 ml injected of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine Formula B three-dose regimen with 28 days interval between doses. Injected intramuscularly in left anterolateral thigh.
Active Comparator: Registered DTwP-Hepatitis B-Hib Vaccine and IPV (Sinovac) ®; 0,5 ml of DTwP-Hepatitis B-Hib Vaccine and IPV (Sinovac)® injected three-dose regimen with 28 days interval between doses.	Biological: Registered DTwP-Hepatitis B-Hib Vaccine and IPV (Sinovac)®; The control group will receive 0,5 ml of Registered DTwP-Hepatitis B-Hib vaccine and 0,5 ml IPV (Sinovac)® injected in three-dose regimen with 28 days interval between doses. Registered DTwP-Hepatitis B-Hib Vaccine are injected intramuscularly into the left antero-lateral thigh region. IPV (Sinovac)® vaccine are injected intramuscularly into the right mid-lateral thigh region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety of the DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine within 7 days after each dose	Safety of the DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine within 7 days after each dose	From enrollment to 7 days after first dose
Phase II: Immunogenicity of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine	Protectivity of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine	From enrollment up to 28 days after third dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I: Safety of the vaccine within 28 days after last dose	Number and percentage of solicited and unsolicited adverse events within 28 days after each dose	From enrollment to 28 days after each dose
Phase I: Safety of the vaccine within 6 months after last dose	Number and percentage of subjects with serious adverse events until 6 months after last dose	From enrollment up to 6 months after the last dose
Phase I: Comparison of safety within 28 days after each dose between vaccines and active control	Comparison of number and percentage of subjects with adverse events between vaccine and control group within 28 days after each dose	From enrollment to 28 days after each dose
Phase I: Comparison of safety until 6 months after last dose between vaccines and active control	Comparison of number and percentage of subjects with serious adverse events between vaccine and control group until 6 months after last dose	From enrollment to 6 months after last dose
Phase I: Routine laboratory evaluation that probably related to the vaccination	Any deviation from routine laboratory evaluation that probably related to the dosing 7 days after first dose.	From enrollment to 7 days after first dose
Phase I: Serological response to diphteria toxoid and tetanus toxoid	Serological response to diphtheria toxoid, tetanus toxoid: GMT, percentage of infants with titer ≥ 0.01 IU/ml, ≥ 0.1 IU/ml percentage of infants with increasing antibody titer ≥ 4 times and/or percentage of infants with transition of seronegative to seropositive.	28 days after the last dose immunization
Phase I: Serological response to the pertussis component (agglutinins)	GMT, percentage of infants with titer ≥ 40, ≥ 80 and ≥ 320 (1/dil.), percentage of infants with increasing antibody titer ≥ 4 times	28 days after the last dose immunization
Phase I: Geometric mean of anti-HbsAg	Percentage of infants with titer ≥ 10mIU/ml, percentage of infants with increasing antibody titer ≥ 4 times and/ or percentage of infants with transition of seronegative to seropositive.	28 days after the last dose immunization
Phase I: Serological response to Hib/PRP	GMT, percentage of infants with titer ≥ 1 μg /ml; ≥ 0.15 μg /ml percentage of infants with increasing antibody titer ≥ 4 times and/or percentage of infants with transition of seronegative to seropositive	28 days after the last dose immunization
Phase I: Serological response to polio type 1, 2, and 3 (humoral immunity)	GMT, percentage of infants with titer ≥ 8, percentage of infants with transition of seronegative to seropositive	28 days after the last dose immunization
Phase II: Serological response to diphtheria toxoid, tetanus toxoid	GMT, percentage of infants with titer ≥ 0.01 IU/ml, ≥ 0.1 IU/ml percentage of infants with increasing antibody titer ≥ 4 times and/or percentage of infants with transition of seronegative to seropositive	28 days after the last dose immunization
Phase II: Serological response to the pertussis component (agglutinins)	GMT, percentage of infants with titer ≥ 40, ≥ 80 and ≥ 320 (1/dil.), percentage of infants with increasing antibody titer ≥ 4 times	28 days after the last dose immunization
Phase II: Geometric mean of anti-HbsAg	percentage of infants with titer ≥ 10mIU/ml, percentage of infants with increasing antibody titer ≥ 4 times and/ or percentage of infants with transition of seronegative to seropositive.	28 days after the last dose immunization
Phase II: Serological response to Hib/PRP	GMT, percentage of infants with titer ≥ 1 μg /ml; ≥ 0.15 μg /ml percentage of infants with increasing antibody titer ≥ 4 times and/or percentage of infants with transition of seronegative to seropositive	28 days after the last dose immunization
Phase II: Serological response to polio type 1, 2, and 3 (humoral immunity)	GMT, percentage of infants with titer ≥ 8, percentage of infants with transition of seronegative to seropositive	28 days after the last dose immunization
Phase II: Safety of vaccine within 30 minutes after immunization	Local reaction and systemic events occurring within 30 minutes after immunization	30 minutes after immunization
Phase II: Safety of vaccine within 7 days after immunization	Local reaction and systemic events occurring within 7 days after immunization	Within 7 days after immunization
Phase II: Safety of vaccine after 7 days to 28 days following the vaccination	Local reaction and systemic events occurring after the 7 days to 28 days following the vaccination	From 7 days to 28 days following the vaccination

Collaborators and Investigators

• Sponsor: PT Bio Farma
• Collaborators: Faculty of Medicine Universitas Padjadjaran

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2025
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: November 13, 2024
• First Submitted That Met QC Criteria: November 13, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: Hexa 010224

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
• product manufactured in and exported from the U.S.: No