Clinical trial NCT02219256: A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of TAK-079 in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autoimmune Disease
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2014-08-18
Enrollment: 74
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
timeFrame: First dose up to Day 94
measure: Number of Participants Who Meet the Takeda Development Centre (TDC) Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose
timeFrame: First dose up to Day 78
measure: Number of Participants Who Meet the TDC Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose
timeFrame: First dose up to Day 78
measure: Number of Participants Who Meet the TDC Markedly Abnormal Criteria for Safety 12-lead Electrocardiogram (ECG) Parameters at Least Once Post Dose
timeFrame: First dose up to Day 78
Secondary outcomes:
measure: Cmax: Maximum Observed Serum Concentration for TAK-079
timeFrame: Day 1 pre-dose and at multiple time-points (up to Day 78) post-dose
measure: AUClast: Area Under the Serum Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-079
timeFrame: Day 1 pre-dose and at multiple time points (up to Day 78) post-dose
measure: AUC∞: Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAK-079
timeFrame: Day 1 pre-dose and at multiple time-points (up to Day 78) post-dose
measure: Percentage of Participants With Positive Antidrug Antibody (ADA) and Neutralizing Antibody (Nab)
timeFrame: Baseline up to Day 78
Other outcomes:
Locations:
city: Headington
country: United Kingdom
state: Oxford
city: London
country: United Kingdom
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: 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.