A Phase 1 MT203 Single-dose Study to Evaluate Safety, PK and PD

Healthy Volunteers Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02354599
• Other study ID #: MT203/CPH-001
• Secondary ID: U1111-1163-4003
• Status: Recruiting
• Phase: Phase 1
• First received: November 7, 2014
• Last updated: January 29, 2015
• Start date: November 2014
• Est. completion date: May 2015

Study information

• Verified date: January 2015
• Source: Takeda
• Contact: Takeda Study Registration Call Center
• Phone: +1-800-778-2860 (USA & EU
• Email: medicalinformation[@]tpna.com
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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

Description:

The drug being tested in this study is called MT-203 (Namilumab), which is a human immunoglobulin G1 (IgG1) mAb potently and specifically neutralizing human and macaque GM-CSF(granulocyte macrophage colony stimulating factor).

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 whome 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 wil 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 Japanee participants) Cohort 2:- MT203 150 mg (6 healthy Japanese participants); Matching Placebo (2 healthy Japanee participants) Cohort 3:- MT203 300 mg (6 healthy Japanese participants); Matching Placebo (2 healthy Japanee 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• 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 kg and has a body mass index (BMI) between 18.5 and 25.0 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:

• 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 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 during the prescribed period.

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, e.g. forced expiratory volume in the first second (FEV1) <70% of the predicted value.

18. The participant has poor peripheral venous access. 19. The participant has undergone whole blood collection of at least 200 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: ALT and/or AST >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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• MT203 80 mg or matching Placebo
MT203 80 mg or matching placebo injection
• MT203 150mg or matching Placebo
MT203 150mg or matching placebo injection
• MT203 300 mg or matching placebo
MT203 300 mg or matching placebo injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants that experience at least 1 treatment-emergent adverse event in non-hemodialysis participants	The frequencies of all adverse events observed during the observation period will be tabulated by type and seriousness. An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a drug whether or not it is considered related to the drug.	Up to Day 85	Yes
Primary	Percentage of participants who meet markedly abnormal criteria for vital sign measurements	Vital signs including body temperature ( infra-axillary measurement), supine blood pressure (after 5 minutes resting), respiration rate and pulse (bpm) will be measured at the visits and times specified in the protocol.	Up to 85 days	Yes
Primary	Weight change from baseline	Change in weight from the baseline.	Up to 85 days	Yes
Primary	Percentage of participants who meet markedly abnormal criteria for safety 12-lead electrocardiogram (ECG) parameters	12-lead ECG findings at baseline changes from baseline for each observation period.	Up to 85 days	Yes
Primary	Percentage of participants with markedly abnormal clinical laboratory evaluations	The percentage of participants with any markedly abnormal standard safety laboratory values, including hematology, serum chemistries, and urinalysis.	Up to 85 days	Yes
Primary	Percentage of markedly abnormal participants in pulmonary function monitoring	Pulmonary function monitoring will include chest X-ray, assessment of MRC Breathlessness questionnaire, and pulmonary function test [Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC), and Peak Expiratory Flow Rate (PEF)] and oxygen saturation (SpO2) will be recorded.	Up to 85 days	Yes
Secondary	Maximum observed serum concentrations (Cmax) of MT203	Serum concentration of MT203: The concentration of MT203 in serum will be determined using a validated ELISA (Enzyme linked immunosorbent assay).	Up to 85 days	No
Secondary	Plasma concentration of total GM-CSF	Plasma concentration of total GM-CSF: The concentration of total GM-CSF in plasma will be determined using an ECL (Electrochemiluminescence) assay after MT203 and GM-CSF are dissociated.	Up to 85 days	No
Secondary	Presence of anti-MT203 antibody in serum	Immunogenicity (anti-MT203 antibodies, neutralizing antibodies): Anti-MT203 antibodies in serum will be determined using a validated ECL assay. Neutralizing antibodies will only be determined in samples that are positive for serum anti-MT203 antibodies.	Up to 85 days	No