A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of TAK-079 in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to characterize the pharmacokinetic and safety and tolerability profile of TAK-079 following a single intravenous (IV) infusion or subcutaneous (SC) administration at escalating dose levels in healthy participants.

Detailed Description
-----------------
The drug being tested in this study is TAK-079. TAK-079 is being tested to find a safe and well-tolerated dose and to assess how TAK-079 is processed by the body. This study will look at pharmacokinetics, side effects, and laboratory results in people who take TAK-079 and is designed as a randomized single dose-rising study. Therefore, each subsequent cohort will not start until the previous cohort has completed and the results are reviewed. Each participant will receive TAK-079 or placebo once only as an IV infusion or by SC administration. The starting dose for IV will be 0.0003 mg/kg and SC dose of 0.01 or 0.03 mg/kg was determined based on the no-observed-adverse-effect-level (NOAEL) results from the 13-week good laboratory practice (GLP) monkey toxicology study. If this dose is well-tolerated, the next group will receive a higher dose, etc, until a maximal tolerated dose is reached with the highest dose not to exceed 1.0 mg/kg. This single-center trial will be conducted in the United Kingdom. The overall time to participate in this study is up to 17 weeks. Participants will make 11 visits to the clinic, including one 10-day period of confinement in the clinic. All participants will be contacted by telephone 14 days after the last visit to the clinic for a follow-up assessment.

Official Title
-----------------
A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Safety, Tolerability and Pharmacokinetic Study of Escalating Single Intravenous Infusion and Subcutaneous Administration of TAK-079 in Healthy Subjects

Conditions
-----------------
Autoimmune Disease

Intervention / Treatment
-----------------
* Drug: TAK-079
* Drug: Placebo to TAK-079


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Is a healthy male or female with no child bearing potential who is 18 to 55 years of age inclusive. The subject weighs at least 70 kilogram (kg) for cohort 1 and subsequent cohorts 50 kg (110.2 lb) and less than 100 kg (220.5 lb) and has a body mass index (BMI) range of 18.5 to 30 kilogram per square meter (kg/m^2), inclusive at Screening Visit 1. A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 6 months after last dose of study medication. Exclusion Criteria: Has received any investigational compound within the last 3 months or 5*T1/2 of the investigational compound,whichever is longer, prior to the day of study medication (Day 1). Has received any live vaccinations, within the last 3 months prior to Screening or is expected to receive any vaccinations during the study or for 1 month after the Day 78 Study Exit visit. Has received any other biologic medical products at any time in the past. Has a positive drug or alcohol screening result, or a history of drug or alcohol abuse. Has a positive test result for hepatitis or human immunodeficiency virus antibody. Has any signs of an acute infection or history of frequent or chronic infection, or herpes zoster. Has active or latent tuberculosis (TB) Considered unfit for the study by the Principal Investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TAK-079 0.0003 mg/kg<br>TAK-079 0.0003 mg/kg, infusion, intravenously, once. | Drug: TAK-079<br>* TAK-079 solution<br>|
| Experimental: Cohort 2-9: TAK-079 TBD<br>TAK-079, infusion, intravenously or subcutaneously, once. Dose to be determined from data collected in previous IV or SC Cohort(s) | Drug: TAK-079<br>* TAK-079 solution<br>|
| Placebo Comparator: Placebo to TAK-079<br>Placebo to TAK-079, infusion, intravenously or subcutaneously, once. | Drug: Placebo to TAK-079<br>* Placebo to TAK-079 solution<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | An Adverse Event (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. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. AE was assessed according to severity; mild (transient and easily tolerated by the participant), moderate (causes the participant discomfort and interrupts the participant's usual activities) and severe (causes considerable interference with the participant's usual activities). | First dose up to Day 94 | 
| Number of Participants Who Meet the Takeda Development Centre (TDC) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose |  | First dose up to Day 78 | 
| Number of Participants Who Meet the TDC Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose |  | First dose up to Day 78 | 
| Number of Participants Who Meet the TDC Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose |  | First dose up to Day 78 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax: Maximum Observed Serum Concentration for TAK-079 |  | Day 1 pre-dose and at multiple time-points (up to Day 78) post-dose | 
| AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079 |  | Day 1 pre-dose and at multiple time points (up to Day 78) post-dose | 
| AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-079 |  | Day 1 pre-dose and at multiple time-points (up to Day 78) post-dose | 
| Percentage of Participants With Positive Antidrug Antibody (ADA) and Neutralizing Antibody (Nab) | Results for ADA analysis were reported. | Baseline up to Day 78 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug therapy