Phase 1/2 Study of TAK-850 Intramuscular Injection in Healthy Pediatric Participants

An Open-label, Multi-center, Phase 1/2 Study to Evaluate the Safety and Immunogenicity of an Intramuscular Injection of TAK-850 in Healthy Pediatric Subjects

The purpose of this study is to evaluate the safety and immunogenicity of an intramuscular injection of TAK-850 in healthy pediatric Japanese participants.

Study Overview

• Status: Completed
• Conditions: Influenza Infection
• Intervention / Treatment: Drug: TAK-850 0.5 mL injection; Drug: TAK-850 0.25 mL injection

Detailed Description

The drug being tested in this study is called TAK-850, that is under development as a vaccine for influenza infection. This study will evaluate the safety and immunogenicity of TAK-850 in healthy Japanese children when given as an intramuscular injection.

The study will enroll approximately 99 participants (33 per treatment group) to receive TAK-850 in open label fashion, The participants will be assigned to each treatment group as follows:

• a single intramuscular injection of TAK-850/0.5 mL in 13 to 19 years old healthy Japanese children,
• Two injections of TAK-850/0.5 mL in 3 to 12 years old healthy Japanese children,
• Two injections of TAK-850/0.25 mL in 6 to 35 months old healthy Japanese children.

The overall time to participate in this trial is 22 days (13-19 years old) or 43 days (6 months to 12 years old). Participants will make up to 2 visits (13-19 years old) or 3 visits (6 months to 12 years old) to the site.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Chuou-ku, Tokyo, Japan
    • Setagaya-ku, Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 19 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. In the opinion of the investigator or the subinvestigator, the participant and/or his/her representative and his/her guardian is capable of understanding and complying with protocol requirements.
2. The participant's representative can sign and date a written, informed consent form prior to the initiation of any study procedures.
3. The participant is a healthy Japanese child.
4. The participant is aged 6 months to 19 years, inclusive, at the time of starting to receive the study vaccine.
5. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to routinely use adequate contraception from signing of informed consent until 12 weeks after the administration.

Exclusion Criteria:

[Only for participants at the age of 6-35 months old]

1. The participant is a preterm newborn (gestational age was less than 37 weeks) or a low-birth-weight newborn (birth weight was less than 2500 g).
2. The participant has received any investigational compound within 4 months prior to the initial injection of study vaccine.
3. The participant has been vaccinated with seasonal influenza vaccine within 6 months prior to the initial injection of study vaccine.
4. The participant has a history of influenza infection within 6 months prior to the initial injection of study vaccine.
5. The participant is a study site employee, an immediate family member of such an employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress.
6. The participant has uncontrolled, clinically significant manifestations of neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, endocrine or other disorders, which may impact the ability of the participant to participate or potentially confound the study results.
7. The participant has an armpit temperature ≥ 37.5°C prior to the initial injection of study vaccine on Day 1.
8. The participant has any medically diagnosed or suspected immune deficient condition.
9. The participant has an immune compromising condition or disease, or is currently undergoing a form of treatment or was undergoing a form of treatment that can be expected to influence immune response within 30 days prior to the initial injection of study vaccine. Such treatments include, but are not limited to, systemic or high dose inhaled corticosteroids (> 800 μg/day of beclomethasone dipropionate or equivalent; the use of inhaled and nasal steroids that do not exceed this level will be permitted), radiation treatment or other immunosuppressive or cytotoxic drugs.
10. The participant has received antipyretics within 4 hours prior to the initial injection of study vaccine.
11. The participant has a history of Guillain-Barré Syndrome, demyelinating disorders (including acute disseminated encephalomyelitis [ADEM] and multiple sclerosis) or convulsions.
12. The participant has a functional or surgical asplenia.
13. The participant has a rash, other dermatologic conditions or tattoos which may interfere with the evaluation of injection site reaction as determined by the Investigator.
14. The participant has a history of, or is infected with the Hepatitis B Virus (HBsAgs), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV).
15. The participant has a known hypersensitivity to any component of TAK-850.
16. The participant has a history of severe allergic reactions or anaphylaxis.
17. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to the initial injection of study vaccine or is unwilling to agree to abstain from alcohol and drugs throughout the study.
18. The participant has received any blood products (e.g. blood transfusion or immunoglobulin) within 90 days prior to the initial injection of study vaccine.
19. The participant has received a live vaccine within 4 weeks (28 days) or an inactivated vaccine within 2 weeks (14 days) prior to the initial injection of study vaccine.
20. If female, the participant is pregnant or lactating or intending to become pregnant before signing informed consent, during, or within 1 month after participating in this study; or intending to donate ova during such time period.
21. The participant has donated whole blood ≥ 200 mL within 4 weeks (28 days), ≥ 400 mL within 12 weeks (84 days), ≥ 800 mL within 52 weeks (364 days), or blood components within 2 weeks (14 days) prior to the initial injection of study vaccine.

22. In the opinion of the investigator or subinvestigator, the participant is unlikely to comply with protocol requirements or is considered ineligible for any other reason.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TAK-850 0.5 mL injection (13-19 years of age); Single intramuscular injection of TAK-850 0.5 mL in participants aged 13-19 years	Drug: TAK-850 0.5 mL injection; TAK-850 injection
Experimental: TAK-850 0.5 mL injection (3-12 years of age); Two intramuscular injections of TAK-850 0.5 mL in participants aged 3-12 years old.	Drug: TAK-850 0.5 mL injection; TAK-850 injection
Experimental: TAK-850 0.25 mL injection (6-35 months of age); Two intramuscular injections of TAK-850 0.25 mL in participants aged 6-35 months old.	Drug: TAK-850 0.25 mL injection; TAK-850 intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 6-35 Months Old Group	Local reactions and systemic events were recorded using a diary. Number of participants with local reactions (Injection site tenderness, Injection site ecchymosis, Irritability postvaccinal) and systemic events (Pyrexia, sweaty, vomiting, crying abnormal, inappetence, somnolence, sleeplessness) were reported. Participants may be represented in more than 1 category.	Up to 21 days after any vaccination
Number of Participants With Solicited Local and Systemic Adverse Events (AEs) for 3-12 Years Old Group and 13-19 Years Old Group	Local reactions and systemic events were recorded using a diary. Number of participants with local reactions (Injection site pain, Injection site redness, Injection site swelling, Injection site induration, Injection site tenderness, Injection site ecchymosis) and systemic events (Pyrexia, malaise, chills, fatigue, headache, sweaty, myalgia, nausea, vomiting) were reported. Participants may be represented in more than 1 category.	Up to 21 days after any vaccination
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; or congenital anomaly; or a medically important event. AEs included both SAE and non-SAE.	Up to 21 days after any vaccination
Percentage of Participants With Seroprotection in Hemagglutination Inhibition (HI) Antibody Titer (Egg-Derived Antigen) of >=40: 21 Days After the Vaccination for 13-19 Years Old Group	Seroprotection rate was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination for the age group of 13-19 years. Seroprotection rate was defined as the percentage of participants with HI antibody titer of >=40.	Day 22 (21 days after Vaccination)
Percentage of Participants With Seroprotection in HI Antibody Titer (Egg-Derived Antigen) of >=40: 21 Days After the Second Vaccination for 6-35 Months Old Group and 3-12 Years Old Group	Seroprotection rate was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after second vaccination for two age groups: 6-35 months and 3-12 years. Seroprotection rate was defined as the percentage of participants with HI antibody titer of >=40.	Day 43 (21 days after Vaccination 2)
Percentage of Participants With Seroconversion in Hemagglutination Inhibition (HI) Antibody Titer (Egg-Derived Antigen): 21 Days After the Vaccination for 13-19 Years Old Group	Seroconversion rate was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination for the age group of 13-19 years. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from baseline (with a baseline HI antibody titer of >=10), or achieving a HI antibody titer of >=40 (with a baseline HI antibody titer of <10) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain).	Day 22 (21 days after Vaccination)
Percentage of Participants With Seroconversion in HI Antibody Titer (Egg-Derived Antigen): 21 Days After the Second Vaccination for 6-35 Months Old Group and 3-12 Years Old Group	Seroconversion rate was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after second vaccination for two age groups: 6-35 months and 3-12 years. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from baseline (with a baseline HI antibody titer of >=10), or achieving a HI antibody titer of >=40 (with a baseline HI antibody titer of <10) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain).	Day 43 (21 days after Vaccination 2)
Geometric Mean Fold Increase (GMFI) in HI Antibody Titer (Egg-Derived Antigen) From Baseline to 21 Days After the Vaccination for 13-19 Years Old Group	GMFI from baseline in HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination for the age group of 13-19 years.	Day 22 (21 days after Vaccination)
GMFI in HI Antibody Titer (Egg-Derived Antigen) From Baseline to 21 Days After the Second Vaccination for 6-35 Months Old Group and 3-12 Years Old Group	GMFI from baseline in HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after second vaccination for two age groups: 6-35 months and 3-12 years.	Day 43 (21 days after Vaccination 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Seroprotection in HI Antibody Titer (Egg-Derived Antigen) of >= 40: 21 Days After the First Vaccination for 6-35 Months Old Group and 3-12- Years Old Group	Seroprotection rate was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after first vaccination for two age groups: 6-35 months and 3-12 years. Seroprotection rate was defined as the percentage of participants with HI antibody titer of >=40.	Day 22 (21 days after Vaccination 1)
Percentage of Participants With Seroconversion in HI Antibody Titer (Egg-Derived Antigen): 21 Days After the First Vaccination for 6-35 Months Old Group and 3-12 Years Old Group	Seroconversion rate was measured by HI antibody titer for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after the first vaccination for two age groups: 6-35 months and 3-12 years. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from baseline (with a baseline HI antibody titer of >=10), or achieving a HI antibody titer of >=40 (with baseline HI antibody titer of <10) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain).	Day 22 (21 days after Vaccination 1)
GMFI in HI Antibody Titer (Egg-Derived Antigen) From Baseline to 21 Days After the First Vaccination for 6-35 Months Old Group and 3-12 Years Old Group	GMFI from baseline in HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after first vaccination for two age groups: 6-35 months and 3-12 years.	Day 22 (21 days after Vaccination 1)
Geometric Mean Titer (GMT) of HI Antibody Titer (Egg-Derived Antigen)	GMT of HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination. Analysis after Vaccination 2 is only applicable for 6-35 Months old group and 3-12 Years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroprotection in Single Radial Hemolysis (SRH) Antibody Titer (Egg- Derived Antigen) of >=25 Square Millimeter (mm^2)	Seroprotection rate was measured by SRH antibody titer (egg- derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroprotection rate was defined as the percentage of participants with SRH antibody titer of >=25 mm^2. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroconversion in SRH Antibody Titer (Egg-Derived Antigen)	Seroconversion rate was measured by SRH antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroconversion rate was defined as the percentage of participants achieving a minimal 50% increase from baseline (with a baseline SRH antibody titer of >4 mm^2) or achieving a SRH antibody titer of >=25 mm^2 (with baseline SRH antibody titer of <=4 mm^2) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain). Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
GMFI in SRH Antibody Titer (Egg-Derived Antigen) From Baseline to 21 Days After Each Vaccination	GMFI from baseline in SRH antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6 -35 months old group and 3-12 years old group)
GMT of SRH Antibody Titer (Egg-Derived Antigen)	GMT of SRH antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroprotection in HI Antibody Titer (Vero Antigen) of >=40	Seroprotection rate was measured by HI antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroprotection rate was defined as the percentage of participants with HI antibody titer of >=40. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroconversion in HI Antibody Titer (Vero Antigen)	Seroconversion rate was measured by HI antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from baseline (with a baseline HI antibody titer of >=10), or achieving a HI antibody titer of >=40 (with baseline HI antibody titer of <10) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain). Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
GMFI in HI Antibody Titer (Vero Antigen) From Baseline to 21 Days After Each Vaccination	GMFI from baseline in HI antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
GMT of HI Antibody Titer (Vero Antigen)	GMT of HI antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroprotection in SRH Antibody Titer (Vero Antigen) of >= 25 mm^2	Seroprotection rate was measured by SRH antibody titer (Vero Antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroprotection rate was defined as the percentage of participants with SRH antibody titer of >=25 mm^2. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
Percentage of Participants With Seroconversion in SRH Antibody Titer (Vero Antigen)	Seroconversion rate was measured by SRH antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Seroconversion rate was defined as the percentage of participants achieving a minimal 50% increase from baseline (with a baseline SRH antibody titer of >4 mm^2), or achieving a SRH antibody titer of >=25 mm^2 (with baseline SRH antibody titer of <=4 mm^2) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain). Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
GMFI in SRH Antibody Titer (Vero Antigen) From Baseline to 21 Days After Each Vaccination	GMFI from baseline in SRH antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination for all groups. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)
GMT of SRH Antibody Titer (Vero Antigen)	GMT of SRH antibody titer (Vero antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after each vaccination. Analysis after Vaccination 2 is only applicable for 6-35 months old group and 3-12 years old group.	Day 22 (21 days after Vaccination 1 for all groups), Day 43 (21 days after Vaccination 2 for 6-35 months old group and 3-12 years old group)

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: February 13, 2015
• First Submitted That Met QC Criteria: February 13, 2015
• First Posted (Estimate): February 20, 2015

Study Record Updates

• Last Update Posted (Estimate): April 7, 2016
• Last Update Submitted That Met QC Criteria: March 8, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Prevention
• Other Study ID Numbers: TAK-850/CCT-101; U1111-1166-6015 (Registry Identifier: UTN (WHO)); JapicCTI-152807 (Registry Identifier: JapicCTI)