Vaccine Adverse Reaction, Vaccine Reaction
Conditions
Brief summary
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.
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.
Interventions
BIOLOGICALDTwP-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.
BIOLOGICALDTwP-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.
BIOLOGICALRegistered 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
Sponsors
Faculty of Medicine Universitas Padjadjaran
PT Bio Farma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Weeks to 11 Weeks
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: 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 | Safety of the DTwP-Hepatitis B-Hib-IPV (Bio Farma) vaccine within 7 days after each dose |
| Phase II: Immunogenicity of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine | From enrollment up to 28 days after third dose | Protectivity of DTwP-Hepatitis B-Hib-IPV (Bio Farma) Vaccine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase I: Comparison of safety within 28 days after each dose between vaccines and active control | From enrollment to 28 days after each dose | Comparison of number and percentage of subjects with adverse events between vaccine and control group within 28 days after each dose |
| Phase I: Comparison of safety until 6 months after last dose between vaccines and active control | From enrollment to 6 months after last dose | Comparison of number and percentage of subjects with serious adverse events between vaccine and control group until 6 months after last dose |
| Phase I: Routine laboratory evaluation that probably related to the vaccination | From enrollment to 7 days after first dose | Any deviation from routine laboratory evaluation that probably related to the dosing 7 days after first dose. |
| Phase I: Serological response to diphteria toxoid and tetanus toxoid | 28 days after the last dose immunization | 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. |
| Phase I: Serological response to the pertussis component (agglutinins) | 28 days after the last dose immunization | GMT, percentage of infants with titer ≥ 40, ≥ 80 and ≥ 320 (1/dil.), percentage of infants with increasing antibody titer ≥ 4 times |
| Phase I: Geometric mean of anti-HbsAg | 28 days after the last dose immunization | 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. |
| Phase I: Serological response to Hib/PRP | 28 days after the last dose immunization | 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 |
| Phase I: Serological response to polio type 1, 2, and 3 (humoral immunity) | 28 days after the last dose immunization | GMT, percentage of infants with titer ≥ 8, percentage of infants with transition of seronegative to seropositive |
| Phase I: Safety of the vaccine within 28 days after last dose | From enrollment to 28 days after each dose | Number and percentage of solicited and unsolicited adverse events within 28 days after each dose |
| Phase II: Serological response to the pertussis component (agglutinins) | 28 days after the last dose immunization | GMT, percentage of infants with titer ≥ 40, ≥ 80 and ≥ 320 (1/dil.), percentage of infants with increasing antibody titer ≥ 4 times |
| Phase II: Geometric mean of anti-HbsAg | 28 days after the last dose immunization | 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. |
| Phase II: Serological response to Hib/PRP | 28 days after the last dose immunization | 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 |
| Phase II: Serological response to polio type 1, 2, and 3 (humoral immunity) | 28 days after the last dose immunization | GMT, percentage of infants with titer ≥ 8, percentage of infants with transition of seronegative to seropositive |
| Phase II: Safety of vaccine within 30 minutes after immunization | 30 minutes after immunization | Local reaction and systemic events occurring within 30 minutes after immunization |
| Phase II: Safety of vaccine within 7 days after immunization | Within 7 days after immunization | Local reaction and systemic events occurring within 7 days after immunization |
| Phase II: Safety of vaccine after 7 days to 28 days following the vaccination | From 7 days to 28 days following the vaccination | Local reaction and systemic events occurring after the 7 days to 28 days following the vaccination |
| Phase II: Serological response to diphtheria toxoid, tetanus toxoid | 28 days after the last dose immunization | 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 |
| Phase I: Safety of the vaccine within 6 months after last dose | From enrollment up to 6 months after the last dose | Number and percentage of subjects with serious adverse events until 6 months after last dose |
Countries
Indonesia
Contacts
Primary ContactRini Mulia Sari, MD
Backup ContactMita Puspita, MD
Outcome results
None listed