Clinical trial NCT02354599: Single-Dose Study of MT203
Official title: A Randomized, Single-center, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate Safety and Pharmacokinetics of Single Subcutaneous Injection of MT203 in Healthy Adult Japanese and Caucasian Male Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Randomized, double-blind, placebo-controlled, single-dose subcutaneous administration study
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-02-03
Enrollment: 32
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate safety, pharmacokinetics and pharmacodynamics of single subcutaneous injection of MT203 in healthy adult Japanese and Caucasian male participants.

Detailed description: The drug being tested in this study is called MT203 (Namilumab), which is a human immunoglobulin G1 (IgG1) mAb potently and specifically neutralizing human and macaque granulocyte macrophage colony stimulating factor (GM-CSF). This study will consist of Cohorts 1 to 3 for healthy Japanese participants and Cohort 4 for healthy Caucasian participants. Each cohort will be comprised of 8 participants, of whom 6 participants will be randomized to receive MT203 and 2 participants will be randomized to receive matched placebo.

The study population for the study will consist of 24 Japanese and 8 Caucasian healthy participants. Participants will be assigned to 4 cohorts which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need)::

Cohort 1:- MT203 80 mg (6 healthy Japanese participants); Matching Placebo (2 healthy Japanese participants) Cohort 2:- MT203 150 mg (6 healthy Japanese participants); Matching Placebo (2 healthy Japanese participants) Cohort 3:- MT203 300 mg (6 healthy Japanese participants); Matching Placebo (2 healthy Japanese participants) Cohort 4:- MT203 150 mg (6 healthy Caucasian participants); Matching Placebo (2 healthy Caucasian participants).

Dosing of the Caucasian participants (Cohort 4) may occur in parallel with dosing in Japanese participants (Cohorts 1 to 3). Dose escalation will occur in Japanese Cohorts, independent from Cohort 4. The dose escalation will only occur following a review of the blinded safety/tolerability data up to Day 15 from the previous cohort. All participants will receive a single dose on Day 1, admitted from Day -1 to Day 15. Participants will return to the study unit for the pharmacokinetic, pharmacodynamic and safety assessment on Days 22, 29, 43, 57, 71 and 85.

This trial will be conducted in Japan.Overall time to participate in this trial is 85 days.

Eligibility criteria: Inclusion Criteria: -

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
2. The participant signs and dates a written, informed consent form and any required privacy authorizations prior to the initiation of any study procedures.
3. The participant is a healthy adult male of Japanese or Caucasian (born to Caucasian parents and grandparents).
4. The participant is aged 20 to 45 years, inclusive, at the time of informed consent.
5. The participant weighs at least 50 kilogram (kg) and has a body mass index (BMI) between 18.5 and 25.0 kilogram per square meter (kg/m2) (for Japanese) or between 18.5 and 30.0 kg/m2 (for Caucasian), inclusive at screening and Day-1.
6. A male participant who is nonsterilized 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 18 weeks (126 days) after last dose.

Exclusion Criteria: -

1. The participant has received any investigational compound within 16 weeks (112 days) prior to the first dose of study medication.
2. The participant has received MT203 or other anti-granulocyte-macrophage colony stimulating factor (GM-CSF) drugs in a previous clinical study.
3. The participant has been vaccinated within 4 weeks (28 days) prior to the first dose of study medication or is scheduled to be vaccinated during the study.
4. The participant is an immediate family member, study site employee or may consent under duress.
5. The participant has uncontrolled, clinically significant neurologic, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, or endocrine disease or other abnormalities, which may impact the ability of the participant to participate or potentially confound the study results.
6. History of frequent or chronic infections or herpes zoster.
7. The participant has a history of or currently has significant pulmonary disease, inflammatory disease or autoimmune disease.
8. The participant has a known hypersensitivity to any component of the formulation of MT203.
9. The participant has a positive urine drug result for drugs of abuse at screening. 10. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the screening visit or is unwilling to agree to abstain from alcohol and drugs throughout the study.

11. The participant has taken or requires excluded medications, supplements or food products listed in the Excluded Medications section throughout the study.

12. The participant intends to donate sperm during the course of this study or for 18 weeks after the last dose of study medication.

13. The participant has a history of cancer. 14. Presence, suspicion or history of active tuberculosis (TB) or latent TB infection.

15. The participant has a positive test result for hepatitis B virus (HBV) surface antigen (HBsAg), hepatitis B virus antibody (HBV surface virus antibody \[HBsAb\]/ HBV core antibody \[HBcAb\]), hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody/antigen at screening. However, participants who are positive for HBsAb due to HBV vaccination are exempt.

16. The participant has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 4 weeks (28 days) prior to the first dose of study medication.

17. The participant has clinically relevant decreased lung function, example, forced expiratory volume in the first second (FEV1) less than (\<) 70 percent (%) of the predicted value.

18. The participant has poor peripheral venous access. 19. The participant has undergone whole blood collection of at least 200 milliliter (mL) within 4 weeks (28 days) or at least 400 mL within 12 weeks (84 days) prior to the first dose of study medication.

20. The participant has undergone whole blood collection of at least 800 mL in total within 52 weeks (364 days) prior to the first dose of study medication.

21. The participant has undergone blood component collection within 2 weeks (14 days) prior to the start of study medication administration.

22. Participant has an abnormal (clinically significant) electrocardiogram (ECG) at screening or Day 1.

23. The participant has abnormal laboratory values at screening or Day-1 that suggest a clinically significant underlying disease or participant with the following laboratory abnormalities: Alanine transaminase (ALT) and/or aspartate transaminase (AST) greater than (\>) 1.5 times the upper limit of normal or neutrophil counts and/or monocyte counts \< the lower limit of normal.

24. Participant who, in the opinion of the investigator, is unlikely to comply with the protocol or is unsuitable for the study with any other reason.

Primary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)
timeFrame: Baseline up to Day 85
measure: Number of Participants With TEAEs Related to Vital Signs
timeFrame: Baseline up to Day 85
measure: Number of Participants With TEAEs Related to Body Weight
timeFrame: Baseline up to Day 85
measure: Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG)
timeFrame: Baseline up to Day 85
measure: Number of Participants With TEAEs Related to Lung Functioning Monitoring
timeFrame: Baseline up to Day 85
measure: Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis
timeFrame: Baseline up to Day 85
Secondary outcomes:
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203
timeFrame: Predose and at multiple time points (up to 84 days) post-dose
measure: Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203
timeFrame: Predose and at multiple time points (up to 84 days) post-dose
measure: Maximum Observed Serum Concentrations (Cmax) of MT203
timeFrame: Predose and at multiple time points (up to Day 84) post-dose
measure: Terminal Elimination Half-Life (T1/2) of MT203
timeFrame: Predose and at multiple time points (up to 84 days) post-dose
measure: Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration
timeFrame: Baseline, Hour 24, 72, 120, 168, 240, 336 hours, Day 21, 28, 42, 56, 70, 84
measure: Number of Participants With Positive Response for Anti MT203 Antibody
timeFrame: Baseline, Hour 168, 336, Day 42, 84
Other outcomes:
Locations:
city: Kagoshima-shi
country: Japan
state: Kagoshima
Study officials:
affiliation: Takeda
name: Senior Director
role: STUDY_DIRECTOR
References:
citation: Tanaka S, Harada S, Hiramatsu N, Nakaya R, Kawamura M. Randomized, double-blind, placebo-controlled, phase I study of the safety and pharmacokinetics of namilumab in healthy Japanese and Caucasian men . Int J Clin Pharmacol Ther. 2018 Nov;56(11):507-517. doi: 10.5414/CP203235.