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

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

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.

Study Overview

• Status: Completed
• Conditions: Autoimmune Disease
• Intervention / Treatment: Drug: TAK-079; Drug: Placebo to TAK-079

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
  • Oxford
    • Headington, Oxford, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Is a healthy male or female with no child bearing potential who is 18 to 55 years of age inclusive.
2. 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.
3. 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:

1. 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).
2. 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.
3. Has received any other biologic medical products at any time in the past.
4. Has a positive drug or alcohol screening result, or a history of drug or alcohol abuse.
5. Has a positive test result for hepatitis or human immunodeficiency virus antibody.
6. Has any signs of an acute infection or history of frequent or chronic infection, or herpes zoster.
7. Has active or latent tuberculosis (TB)
8. Considered unfit for the study by the Principal Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Takeda

Publications and helpful links

General Publications

• Fedyk ER, Zhao L, Koch A, Smithson G, Estevam J, Chen G, Lahu G, Roepcke S, Lin J, Mclean L. Safety, tolerability, pharmacokinetics and pharmacodynamics of the anti-CD38 cytolytic antibody TAK-079 in healthy subjects. Br J Clin Pharmacol. 2020 Jul;86(7):1314-1325. doi: 10.1111/bcp.14241. Epub 2020 Feb 22.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: August 14, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): May 3, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Drug therapy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: TAK-079_101; U1111-1155-5857 (Registry Identifier: WHO); 2013-004210-18 (EudraCT Number); 14/LO/1070 (Registry Identifier: NRES)