Phase 1/2 Study of TAK-850 Subcutaneous Injection in Healthy Adults

A Randomized Double Blind Parallel-Group Comparative Phase 1/2 Study to Evaluate the Safety and Immunogenicity of a Single Subcutaneous Injection of TAK-850 in Healthy Adult Subjects

The purpose of this study is to evaluate the safety and immunogenicity of a single subcutaneous injection of TAK-850 as compared to intramuscular injection of TAK-850 in healthy Japanese adults

Study Overview

• Status: Completed
• Conditions: Influenza Infection
• Intervention / Treatment: Drug: Subcutaneous injection of TAK-850; Drug: Intramuscular injection of TAK-850

Detailed Description

The drug being tested in this study is called TAK-850. This drug is being tested to evaluate the safety and immunogenicity of a single subcutaneous injection as compared to a single, intramuscular injection.

A total of 110 healthy participants (55 per group) will take part in this study.

Each participant will be randomly (like flipping a coin) assigned to receive one of the following :

• A single injection of TAK-850, subcutaneously , or
• A single injection of TAK-850, intramuscularly.

Participants will make up to 3 visits to the study site. Total duration of this study is 22 days.

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 49 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements.

  2. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures.

  3. The participant is a healthy Japanese adult male or female. 4. The participant is aged 20 to 49 years, inclusive, at the time of informed consent.

  5. The participant has a body mass index (BMI) between 18.5 and 25.0 kg/m^2, inclusive, at the time of eligibility evaluation.

  6. If the participant is a female of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study.

Exclusion Criteria:

• 1. The participant has received any investigational compound within 4 months prior to the injection of study vaccine.

  2. The participant has been vaccinated with seasonal influenza vaccine within 6 months prior to the injection of study vaccine.

  3. The participant has a history of influenza infection within 6 months prior to the injection of study vaccine.

  4. 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.

  5. The participant has uncontrolled, clinically significant manifestations of neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, endocrine or other disorders, which may impact the ability of the participant to participate or potentially confound the study results.

  6. The participant has an oral temperature ≥37.5 °C prior to the injection of study vaccine on Day 1.

  7. The participant has any medically diagnosed or suspected immune deficient condition.

  8. 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 injection of study vaccine. Such treatments include, but is not limited to, systemic or high dose inhaled corticosteroids (>800 mcg/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.

  9. The participant has received antipyretics within 4 hours prior to the injection of study vaccine.

  10. The participant has a history of Guillain-Barré Syndrome, demyelinating disorders (including acute disseminated encephalomyelitis [ADEM] and multiple sclerosis) or convulsions.

  11. The participant has a functional or surgical asplenia. 12. 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.

  13. The participant has a history of, or is infected with the Hepatitis B Virus (HBsAgs), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV).

  14. The participant has a known hypersensitivity to any component of TAK-850. 15. The participant has a history of severe allergic reactions or anaphylaxis. 16. 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 injection of study vaccine or is unwilling to agree to abstain from alcohol and drugs throughout the study.

  17. The participant has received any blood products (e.g. blood transfusion or immunoglobulin) within 90 days prior to the injection of study vaccine.

  18. The participant has received a live vaccine within 4 weeks (28 days) or an inactivated vaccine within 2 weeks (14 days) prior to the injection of study vaccine.

  19. 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.

  20. 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 injection of study vaccine.

  21. The participant has abnormal laboratory values that suggest a clinically significant underlying disease at the assessment prior to the injection of study vaccine, or the participant has the following lab abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 3 times the upper limits of normal.

  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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TAK-850 0.5 mL (subcutaneous); Single subcutaneous injection of TAK-850	Drug: Subcutaneous injection of TAK-850; TAK-850 0.5 mL, Subcutaneous injection
EXPERIMENTAL: TAK-850 0.5 mL (Intramuscular); Single intramuscular injection of TAK-850	Drug: Intramuscular injection of TAK-850; TAK-850 0.5 mL, Intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Solicited Local and Systemic Adverse Events (AEs)	Number of participants with local reactions (injection site pain, injection site redness, injection site swelling, injection site induration, injection site tenderness, and injection site ecchymosis) and systemic events (pyrexia, malaise, chills, fatigue, headache, sweaty, myalgia, arthralgia, nausea and vomiting) were reported using an electronic diary.	Up to 21 days (Day 22) after vaccination
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)	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 (eg, 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.	Up to 21 days (Day 22) after vaccination
Percentage of Participants With Seroprotection in Hemagglutination Inhibition (HI) Antibody Titer (Egg-derived Antigen) of >=40.	Seroprotection rate as measured by HI antibody titer (egg-derived antigen) was defined as percentage of participants with the HI antibody titer of >=40 for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
Percentage of Participants With Seroconversion in Hemagglutination Inhibition (HI) Antibody Titer (Egg-Derived Antigen)	Seroconversion rate as measured by the HI antibody titer (egg-derived antigen) was defined as percentage of participants achieving a minimal 4-fold increase from the baseline HI antibody titer (baseline >=10) or achieving an HI antibody titer of >=40 (baseline <10) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
Geometric Mean Fold Increase (GMFI) in HI Antibody Titer (Egg-derived Antigen) From Pre-vaccination to 21 Days After Vaccination	GMFI in HI antibody titer (egg-derived antigen) as compared to pre-vaccination was evaluated for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain). Geometric mean and CI were calculated for GMFIs.	Pre-vaccination, 21 Days After vaccination (Day 22)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Reporting Clinically Significant Change From Baseline in Laboratory Values	Laboratory values included hematology, biochemistry and urinalysis tests.	Baseline,up to 21 Days after drug administration (Day 22)
Change From Baseline in Blood Pressure	Change from baseline in systolic and diastolic blood pressure was reported	Baseline, Day 22
Change From Baseline in Pulse	Change from baseline in pulse was reported.	Baseline, Day 22
Change From Baseline in Body Temperature	Change from baseline in body temperature (oral) was reported.	Baseline, Day 22
Geometric Mean Titer (GMT) in HI Antibody Titer (Egg-derived Antigen)	GMT in HI antibody titer (egg-derived antigen) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain) was computed along with 95% CI.	Day 22 (21 days after vaccination)
Percentage of Participants With Seroprotection in SRH Antibody Titer (Egg-derived Antigen) of >=25 mm^2	Seroprotection rate as measured by SRH antibody titer (egg-derived antigen) was defined as percentage of participants with an SRH antibody titer of >=25 mm^2 for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
Percentage of Participants With Seroconversion in SRH Antibody Titer (Egg-Derived Antigen)	Seroconversion rate as measured by the SRH antibody titer (egg-derived antigen) was defined as percentage of participants achieving a minimal 50% increase from the baseline SRH antibody titer (baseline >4 mm^2) or achieving an SRH antibody titer of >=25 mm^2 (baseline <=4 mm^2) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
GMFI in SRH Antibody Titer (Egg-derived Antigen) From Pre-vaccination to 21 Days After Vaccination	GMFI in SRH antibody titer (egg-derived antigen) as compared to baseline pre-vaccination was evaluated for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain). Geometric mean and CI were calculated for GMFIs.	Pre-vaccination, 21 Days after vaccination (Day 22)
GMT in SRH Antibody Titer (Egg-derived Antigen)	GMT in SRH antibody titer (egg-derived antigen) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain) was computed along with 95% CI.	Day 22 (21 days after vaccination)
Percentage of Participants With Seroprotection in HI Antibody Titer (Cell Derived Antigen) of >=40	Seroprotection rate as measured by HI antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) was defined as percentage of participants with an HI antibody titer of >=40 for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
Percentage of Participants With Seroconversion in HI Antibody Titer (Cell Derived Antigen)	Seroconversion rate as measured by the HI antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) was defined as percentage of participants achieving a minimal 4-fold increase from the baseline HI antibody titer (baseline >=10) or achieving an HI antibody titer of >=40 (baseline HI <10) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
GMFI in HI Antibody Titer (Cell Derived Antigen) From Pre-vaccination to 21 Days After Vaccination	GMFI in HI antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) as compared to pre-vaccination was evaluated for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain). Geometric mean and CI were calculated for GMFIs.	Pre-vaccination, 21 Days After vaccination (Day 22)
GMT in HI Antibody Titer (Cell Derived Antigen)	GMT in HI antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain) was computed along with 95% CI.	Day 22 (21 days after vaccination)
Percentage of Participants With Seroprotection in SRH Antibody Titer (Cell Derived Antigen) of >=25 mm^2	Seroprotection rate as measured by SRH antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) was defined as percentage of participants with a SRH antibody titer of >=25 mm^2 for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
Percentage of Participants With Seroconversion in SRH Antibody Titer (Cell Derived Antigen)	Seroconversion rate as measured by the SRH antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) was defined as percentage of participants achieving a minimal 50% increase from the baseline SRH antibody titer (baseline >4 mm^2) or achieving an SRH antibody titer of >=25 mm^2 (baseline <=4 mm^2) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain).	Day 22 (21 days after vaccination)
GMFI in SRH Antibody Titer (Cell Derived Antigen) From Pre-vaccination to 21 Days After Vaccination	GMFI in SRH antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) as compared to pre-vaccination was evaluated for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain). Geometric mean and CI were calculated for GMFIs.	Pre-vaccination, 21 Days After vaccination (Day 22)
GMT in SRH Antibody Titer (Cell Derived Antigen)	GMT in SRH antibody titer (vero antigen, live-vero antigen, and madin-darby canine kidney [MDCK] antigen) for each of the three influenza virus strains (A/H1N1 strain, A/H3N2 strain, and B strain) was computed along with 95% CI.	Day 22 (21 days after vaccination)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Senior VP Clinical Science, Takeda

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2015

Study Registration Dates

• First Submitted: December 5, 2014
• First Submitted That Met QC Criteria: December 5, 2014
• First Posted (ESTIMATE): December 9, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): February 17, 2016
• Last Update Submitted That Met QC Criteria: January 20, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: Prevention
• Other Study ID Numbers: TAK-850/CPH-002; U1111-1164-1969 (REGISTRY: UTN (WHO)); JapicCTI-142724 (REGISTRY: JapicCTI)