Haemophilus Influenzae Type b, Prevention, Healthy Volunteers
Conditions
Keywords
Drug therapy, Safety and immunogenicity of Hib vaccine
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of intramuscular TAK-816 in healthy Japanese infants.
Detailed description
The vaccine being tested in this study is called TAK-816. TAK-816 was being tested to evaluate its safety and immune response after intramuscular (IM) injection with TAK-816. This study evaluated adverse events and the seroprotection rate and geometric mean titer (GMT) of anti-polyribosylribitol phosphate (PRP)-antibodies in participants who were administered TAK-816 IM. The study enrolled 31 participants. All participants received 3 doses of TAK-816 IM at 4-week intervals as part of the primary vaccination and 1 booster vaccination 52 weeks after the third dose of the primary vaccination. This multi-center trial was conducted in Japan. The overall time to participate in this study was 64 weeks. Participants made multiple visits to the clinic including a final visit 4 weeks after last dose of study drug for a follow-up assessment.
Interventions
BIOLOGICALTAK-816
TAK-816 intramuscular injection
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 6 Months
Healthy volunteers
Yes
Inclusion criteria
1. Healthy Japanese infants. 2. Male or female infants aged 2-6 months (≥2 and \<7 months) at the time of the first dose of investigational product (excluding hospitalized infants). 3. Infants whose parents or legal guardians have agreed to cooperate with the investigator during the study period. 4. The legal guardian signed and dated a written, informed consent form prior to the initiation of any study procedures.
Exclusion criteria
1. Any serious acute illness. 2. Any underlying cardiovascular, renal, hepatic, or hematologic disease, and/or developmental disorder. 3. History of possible Haemophilus influenzae type b (Hib) infection. 4. Previously diagnosed immunodeficiency. 5. Documented history of anaphylaxis to any ingredients of the investigational product (e.g., diphtheria toxoid). 6. A history of convulsions. 7. Previous administration of another Hib vaccine. 8. Treatment with any live vaccine during the 27 days before the first dose of TAK-816 or with any inactivated vaccine during the 6 days before dosing. 9. Prior participation in any clinical study or post-marketing clinical study. 10. Previously receipt of blood transfusions, gamma globulin preparations (except monoclonal antibody products not containing any components of Hib as antigens), systemic immunosuppressive therapy, or systemic corticosteroids, or a plan to receive any of these products during the study period. 11. Presence of thrombocytopenia or coagulopathy. 12. Children considered ineligible for the study for other reasons by the investigator or subinvestigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | For 64 Weeks | Adverse events are defined as unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product, regardless of relationship to the medicinal product. Among these, events which are considered possibly associated with a medicinal product are defined as adverse reactions. |
| Number of Participants With Adverse Reactions Related to Body Temperature (Pyrexia) | For 64 Weeks | Body temperature was assessed for 14 days after each vaccination and was recorded by the caregiver in a diary. Adverse reactions related body temperature was reported as pyrexia. |
| Number of Participants With Adverse Reactions Related to Local Reactions | For 64 Weeks | Local Reactions were assessed 14 days after each vaccination and were recorded by the caregiver in a diary. Local reactions (injection site) were erythema, swelling, induration and pain (tenderness). |
| Number of Participants With Adverse Reactions Related to Systemic Reactions | For 64 Weeks | Systemic Reactions were assessed 14 days after each vaccination and were recorded by the caregiver in a diary. Systemic reactions were rash, irritability, crying, decreased appetite, vomiting, diarrhoea, somnolence (sleepiness) and insomnia (sleeplessness). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL | For 64 weeks | Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Hib as an assessment of immunogenicity. |
| Geometric Mean Titer (GMT) of Anti-PRP Antibody | For 64 weeks | Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Hib as an assessment of immunogenicity. |
| Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL | For 64 weeks | Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Haemophilus influenzae type b (Hib) as an assessment of immunogenicity. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 4 investigative sites in Japan from 13 March 2014 to 25 March 2015.
Pre-assignment details
Participants received open-label TAK-816 0.5 mL vaccinations, 3 initial doses and 1 booster.
Participants by arm
| Arm | Count |
|---|---|
| TAK-816 0.5 mL Primary immunization: TAK-816 0.5 mL, intramuscular injection, once on Day 1 and every 28 days for 2 intervals (Days 29 and 57). Booster immunization: TAK-816 0.5 mL, intramuscular injection, once, 52 weeks after the third dose of primary immunization. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | TAK-816 0.5 mL |
|---|---|
| Age, Continuous | 2.54 months STANDARD_DEVIATION 0.587 |
| Age, Customized ≥2 - <3 months | 22 participants |
| Age, Customized <2 months | 0 participants |
| Age, Customized ≥3 - <4 months | 8 participants |
| Age, Customized ≥4 - <5 months | 1 participants |
| Age, Customized ≥5 months | 0 participants |
| Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer Before Primary Immunization <0.15 µg/mL | 4 participants |
| Anti-Polyribosylribitol Phosphate (PRP) Antibody Titer Before Primary Immunization ≥0.15 µg/mL | 27 participants |
| Height | 58.2 cm STANDARD_DEVIATION 2.38 |
| Region of Enrollment Japan | 31 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 14 Participants |
| Simultaneous Vaccination of Diphtheria, Tetanus, Pertussis-Inactivated Polio Vaccine (DPT-IPV) No | 31 participants |
| Simultaneous Vaccination of Diphtheria, Tetanus, Pertussis-Inactivated Polio Vaccine (DPT-IPV) Yes | 0 participants |
| Simultaneous Vaccination of Measles-Rubella (MR) Vaccine No | 31 participants |
| Simultaneous Vaccination of Measles-Rubella (MR) Vaccine Yes | 0 participants |
| Simultaneous Vaccination of Pneumococcal Vaccine No | 31 participants |
| Simultaneous Vaccination of Pneumococcal Vaccine Yes | 0 participants |
| Simultaneous Vaccination of Rotavirus Vaccine No | 4 participants |
| Simultaneous Vaccination of Rotavirus Vaccine Yes | 27 participants |
| Weight | 5.62 kg STANDARD_DEVIATION 0.551 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 30 / 31 |
| serious Total, serious adverse events | 4 / 31 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse events are defined as unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product, regardless of relationship to the medicinal product. Among these, events which are considered possibly associated with a medicinal product are defined as adverse reactions.
Time frame: For 64 Weeks
Population: Full Analysis Set (FAS) included all participants who received at least 1 dose of the study vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-816 0.5 mL | Number of Participants With Adverse Events | 31 participants |
Primary
Number of Participants With Adverse Reactions Related to Body Temperature (Pyrexia)
Body temperature was assessed for 14 days after each vaccination and was recorded by the caregiver in a diary. Adverse reactions related body temperature was reported as pyrexia.
Time frame: For 64 Weeks
Population: FAS included all participants who received at least 1 dose of the study vaccination.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Body Temperature (Pyrexia) | 6 participants |
Primary
Number of Participants With Adverse Reactions Related to Local Reactions
Local Reactions were assessed 14 days after each vaccination and were recorded by the caregiver in a diary. Local reactions (injection site) were erythema, swelling, induration and pain (tenderness).
Time frame: For 64 Weeks
Population: FAS included all participants who received at least 1 dose of the study vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Local Reactions | Injection site erythema | 5 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Local Reactions | Injection site swelling | 1 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Local Reactions | Injection site induration | 1 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Local Reactions | Injection site pain | 0 participants |
Primary
Number of Participants With Adverse Reactions Related to Systemic Reactions
Systemic Reactions were assessed 14 days after each vaccination and were recorded by the caregiver in a diary. Systemic reactions were rash, irritability, crying, decreased appetite, vomiting, diarrhoea, somnolence (sleepiness) and insomnia (sleeplessness).
Time frame: For 64 Weeks
Population: FAS included all participants who received at least 1 dose of the study vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Rash | 0 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Irritability | 0 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Crying | 3 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Decreased appetite | 0 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Vomiting | 1 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Diarrhoea | 5 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Somnolence | 3 participants |
| TAK-816 0.5 mL | Number of Participants With Adverse Reactions Related to Systemic Reactions | Insomnia | 2 participants |
Secondary
Geometric Mean Titer (GMT) of Anti-PRP Antibody
Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Hib as an assessment of immunogenicity.
Time frame: For 64 weeks
Population: FAS, all participants who received at least 1 dose of the study vaccination, with available data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TAK-816 0.5 mL | Geometric Mean Titer (GMT) of Anti-PRP Antibody | Before Primary Immunization (n=31) | 0.354 μg/mL |
| TAK-816 0.5 mL | Geometric Mean Titer (GMT) of Anti-PRP Antibody | At 4 Weeks after Primary Immunization (n=30) | 19.682 μg/mL |
| TAK-816 0.5 mL | Geometric Mean Titer (GMT) of Anti-PRP Antibody | Before Booster Vaccination (n=31) | 3.087 μg/mL |
| TAK-816 0.5 mL | Geometric Mean Titer (GMT) of Anti-PRP Antibody | At 4 Weeks after Booster Vaccination (n=31) | 51.334 μg/mL |
Secondary
Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL
Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Hib as an assessment of immunogenicity.
Time frame: For 64 weeks
Population: FAS, all participants who received at least 1 dose of the study vaccination, with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL | At 4 Weeks after Booster Vaccination (n=31) | 100 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL | Before Primary Immunization (n=31) | 87.1 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL | At 4 Weeks after Primary Immunization (n=30) | 100 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 0.15 μg/mL | Before Booster Vaccination (n=31) | 100 percentage of participants |
Secondary
Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL
Blood was collected and was sent to a central laboratory for the evaluation of anti-PRP antibody titer against Haemophilus influenzae type b (Hib) as an assessment of immunogenicity.
Time frame: For 64 weeks
Population: FAS, all participants who received at least 1 dose of the study vaccination, with available data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL | Before Primary Immunization (n=31) | 16.1 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL | At 4 Weeks after Primary Immunization (n=30) | 100 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL | Before Booster Vaccination (n=31) | 77.4 percentage of participants |
| TAK-816 0.5 mL | Percentage of Participant With Anti-PRP Antibody Titer ≥ 1.0 μg/mL | At 4 Weeks after Booster Vaccination (n=31) | 100 percentage of participants |