Healthy Volunteers
Conditions
Keywords
Randomized, double-blind, placebo-controlled, single-dose subcutaneous administration study
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.
Interventions
DRUGMT203 80 mg or matching Placebo
MT203 80 mg or matching placebo injection
DRUGMT203 150mg or matching Placebo
MT203 150mg or matching placebo injection
DRUGMT203 300 mg or matching placebo
MT203 300 mg or matching placebo injection
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Baseline up to Day 85 |
| Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | Baseline up to Day 85 |
| Number of Participants With TEAEs Related to Vital Signs | Baseline up to Day 85 |
| Number of Participants With TEAEs Related to Body Weight | Baseline up to Day 85 |
| Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | Baseline up to Day 85 |
| Number of Participants With TEAEs Related to Lung Functioning Monitoring | Baseline up to Day 85 |
Secondary
| Measure | Time frame |
|---|---|
| Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline, Hour 24, 72, 120, 168, 240, 336 hours, Day 21, 28, 42, 56, 70, 84 |
| Number of Participants With Positive Response for Anti MT203 Antibody | Baseline, Hour 168, 336, Day 42, 84 |
| Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203 | Predose and at multiple time points (up to 84 days) post-dose |
| Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203 | Predose and at multiple time points (up to 84 days) post-dose |
| Maximum Observed Serum Concentrations (Cmax) of MT203 | Predose and at multiple time points (up to Day 84) post-dose |
| Terminal Elimination Half-Life (T1/2) of MT203 | Predose and at multiple time points (up to 84 days) post-dose |
Countries
Japan
Participant flow
Recruitment details
Participant took part in the study at 1 investigative site in Japan from 25-November-2014 to 20-May-2015.
Pre-assignment details
Healthy Japanese and Caucasian participants were enrolled in the study as 1 of the 4 cohorts Japanese participants in Cohort 1(MT203 80 milligram \[mg\]), Cohort 2 (MT203 150 mg), Cohort 3 (MT203 300 mg) and Caucasian participants in Cohort 4 (MT203 150 mg) to receive MT203, or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1-3: Placebo MT203 placebo -matching, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Japanese participants. | 6 |
| Cohort 1: MT203 80 mg MT203 80 mg, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Japanese participants. | 6 |
| Cohort 2: MT203 150 mg MT203 150 mg, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Japanese participants. | 6 |
| Cohort 3: MT203 300 mg MT203 300 mg, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Japanese participants. | 6 |
| Cohort 4: Placebo MT203 placebo-matching, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Caucasian participants. | 2 |
| Cohort 4: MT203 150 mg MT203 150 mg, injection, subcutaneously, once on Day 1 in the 15 days treatment period in Caucasian participants. | 6 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Pretreatment Event/Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1-3: Placebo | Cohort 1: MT203 80 mg | Cohort 2: MT203 150 mg | Cohort 3: MT203 300 mg | Cohort 4: Placebo | Cohort 4: MT203 150 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 28.2 years STANDARD_DEVIATION 8.89 | 26.0 years STANDARD_DEVIATION 4.05 | 26.5 years STANDARD_DEVIATION 7.79 | 24.2 years STANDARD_DEVIATION 6.85 | 28.0 years STANDARD_DEVIATION 7.07 | 36.0 years STANDARD_DEVIATION 6.29 | 28.2 years STANDARD_DEVIATION 7.56 |
| Alcohol Classification Drank a few days per month | 0 participants | 2 participants | 3 participants | 3 participants | 2 participants | 2 participants | 12 participants |
| Alcohol Classification Drank a few days per week | 2 participants | 0 participants | 1 participants | 1 participants | 0 participants | 2 participants | 6 participants |
| Alcohol Classification Never drank | 4 participants | 4 participants | 2 participants | 2 participants | 0 participants | 2 participants | 14 participants |
| Caffeine Classification Had caffeine consumption | 2 participants | 3 participants | 1 participants | 2 participants | 2 participants | 3 participants | 13 participants |
| Caffeine Classification Had no caffeine consumption | 4 participants | 3 participants | 5 participants | 4 participants | 0 participants | 3 participants | 19 participants |
| Sex/Gender, Customized Male | 6 participants | 6 participants | 6 participants | 6 participants | 2 participants | 6 participants | 32 participants |
| Smoking Classification Ex-smoker | 2 participants | 3 participants | 1 participants | 4 participants | 0 participants | 1 participants | 11 participants |
| Smoking Classification Never Smoked | 4 participants | 3 participants | 5 participants | 2 participants | 2 participants | 5 participants | 21 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 3 / 6 | 1 / 6 | 1 / 6 | 1 / 2 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 2 | 1 / 6 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE)
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-3: Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 3 participants |
| Cohort 1: MT203 80 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 3 participants |
| Cohort 2: MT203 150 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 3: MT203 300 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 4: Placebo | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 1 participants |
| Cohort 4: MT203 150 mg | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | 5 participants |
Primary
Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG)
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to 12-lead Electrocardiograms (ECG) | 0 participants |
Primary
Number of Participants With TEAEs Related to Body Weight
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Body Weight | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Body Weight | 0 participants |
Primary
Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 1 participants |
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 1 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 1 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 1 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Serum Chemistry | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Hematology | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Hematology, Serum Chemistry and Urinalysis | Urinalysis | 0 participants |
Primary
Number of Participants With TEAEs Related to Lung Functioning Monitoring
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 1 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 0 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Lung Functioning Monitoring | 0 participants |
Primary
Number of Participants With TEAEs Related to Vital Signs
Time frame: Baseline up to Day 85
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Cohort 4: Placebo | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
| Cohort 4: MT203 150 mg | Number of Participants With TEAEs Related to Vital Signs | 0 participants |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203
Time frame: Predose and at multiple time points (up to 84 days) post-dose
Population: The pharmacokinetic analysis set as defined as all participants who received the study medication without any major protocol deviations, and met the minimum procedure specified in the study protocol and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1-3: Placebo | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203 | 315573.3 nanogram*day per milliliter (ng*day/mL) | Standard Deviation 47464.44 |
| Cohort 1: MT203 80 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203 | 575180.7 nanogram*day per milliliter (ng*day/mL) | Standard Deviation 126751.71 |
| Cohort 2: MT203 150 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203 | 1238496.3 nanogram*day per milliliter (ng*day/mL) | Standard Deviation 222651.06 |
| Cohort 3: MT203 300 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Infinity (AUC(0-inf)) of MT203 | 559689.3 nanogram*day per milliliter (ng*day/mL) | Standard Deviation 188835.67 |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203
Time frame: Predose and at multiple time points (up to 84 days) post-dose
Population: The pharmacokinetic analysis set as defined as all participants who received the study medication without any major protocol deviations, and met the minimum procedure specified in the study protocol and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1-3: Placebo | Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203 | 286383.2 ng*day/mL | Standard Deviation 44732.15 |
| Cohort 1: MT203 80 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203 | 502017.5 ng*day/mL | Standard Deviation 116382.43 |
| Cohort 2: MT203 150 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203 | 1106605.2 ng*day/mL | Standard Deviation 207794.23 |
| Cohort 3: MT203 300 mg | Area Under the Serum Concentration-Time Curve From Time 0 to Time 84 Days (AUC(0-84d)) of MT203 | 451596.7 ng*day/mL | Standard Deviation 133571.47 |
Secondary
Maximum Observed Serum Concentrations (Cmax) of MT203
Time frame: Predose and at multiple time points (up to Day 84) post-dose
Population: The pharmacokinetic analysis set as defined as all participants who received the study medication without any major protocol deviations, and met the minimum procedure specified in the study protocol and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1-3: Placebo | Maximum Observed Serum Concentrations (Cmax) of MT203 | 8381.3 nanogram per milliliter (ng/mL) | Standard Deviation 1848.65 |
| Cohort 1: MT203 80 mg | Maximum Observed Serum Concentrations (Cmax) of MT203 | 15354.5 nanogram per milliliter (ng/mL) | Standard Deviation 5097.64 |
| Cohort 2: MT203 150 mg | Maximum Observed Serum Concentrations (Cmax) of MT203 | 32580.7 nanogram per milliliter (ng/mL) | Standard Deviation 9061.85 |
| Cohort 3: MT203 300 mg | Maximum Observed Serum Concentrations (Cmax) of MT203 | 10826.7 nanogram per milliliter (ng/mL) | Standard Deviation 3220.93 |
Secondary
Number of Participants With Positive Response for Anti MT203 Antibody
Time frame: Baseline, Hour 168, 336, Day 42, 84
Population: The safety analysis set was defined as all participants who received the study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1-3: Placebo | Number of Participants With Positive Response for Anti MT203 Antibody | 42 Days | 0 participants |
| Cohort 1-3: Placebo | Number of Participants With Positive Response for Anti MT203 Antibody | Baseline | 0 participants |
| Cohort 1-3: Placebo | Number of Participants With Positive Response for Anti MT203 Antibody | 84 Days | 0 participants |
| Cohort 1-3: Placebo | Number of Participants With Positive Response for Anti MT203 Antibody | 336 Hours | 1 participants |
| Cohort 1-3: Placebo | Number of Participants With Positive Response for Anti MT203 Antibody | 168 Hours | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 336 Hours | 1 participants |
| Cohort 1: MT203 80 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 42 Days | 2 participants |
| Cohort 1: MT203 80 mg | Number of Participants With Positive Response for Anti MT203 Antibody | Baseline | 0 participants |
| Cohort 1: MT203 80 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 84 Days | 1 participants |
| Cohort 1: MT203 80 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 168 Hours | 1 participants |
| Cohort 2: MT203 150 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 336 Hours | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With Positive Response for Anti MT203 Antibody | Baseline | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 168 Hours | 1 participants |
| Cohort 2: MT203 150 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 42 Days | 0 participants |
| Cohort 2: MT203 150 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 84 Days | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 42 Days | 1 participants |
| Cohort 3: MT203 300 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 168 Hours | 2 participants |
| Cohort 3: MT203 300 mg | Number of Participants With Positive Response for Anti MT203 Antibody | Baseline | 0 participants |
| Cohort 3: MT203 300 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 336 Hours | 1 participants |
| Cohort 3: MT203 300 mg | Number of Participants With Positive Response for Anti MT203 Antibody | 84 Days | 1 participants |
Secondary
Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration
Time frame: Baseline, Hour 24, 72, 120, 168, 240, 336 hours, Day 21, 28, 42, 56, 70, 84
Population: The pharmacodynamic analysis set was defined as all participants who received the study medication without any major protocol deviations, and met the minimum procedure specified in the study protocol and had evaluable pharmacodynamic data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 123.535 picogram per milliliter (pg/mL) | Standard Deviation 20.4004 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 215.698 picogram per milliliter (pg/mL) | Standard Deviation 33.8697 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 291.852 picogram per milliliter (pg/mL) | Standard Deviation 48.4269 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 387.628 picogram per milliliter (pg/mL) | Standard Deviation 60.4318 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 483.353 picogram per milliliter (pg/mL) | Standard Deviation 77.2963 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 733.440 picogram per milliliter (pg/mL) | Standard Deviation 330.8767 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 653.467 picogram per milliliter (pg/mL) | Standard Deviation 111.0059 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 547.093 picogram per milliliter (pg/mL) | Standard Deviation 81.0675 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 431.300 picogram per milliliter (pg/mL) | Standard Deviation 94.4867 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 325.750 picogram per milliliter (pg/mL) | Standard Deviation 67.8796 |
| Cohort 1-3: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 240.712 picogram per milliliter (pg/mL) | Standard Deviation 44.5704 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 131.165 picogram per milliliter (pg/mL) | Standard Deviation 25.2255 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 366.078 picogram per milliliter (pg/mL) | Standard Deviation 200.2973 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 710.998 picogram per milliliter (pg/mL) | Standard Deviation 202.6718 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 633.093 picogram per milliliter (pg/mL) | Standard Deviation 186.5863 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 415.098 picogram per milliliter (pg/mL) | Standard Deviation 88.4198 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 758.195 picogram per milliliter (pg/mL) | Standard Deviation 157.6988 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 440.092 picogram per milliliter (pg/mL) | Standard Deviation 126.7378 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 740.245 picogram per milliliter (pg/mL) | Standard Deviation 245.6498 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 314.218 picogram per milliliter (pg/mL) | Standard Deviation 65.0007 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 554.973 picogram per milliliter (pg/mL) | Standard Deviation 122.5254 |
| Cohort 1: MT203 80 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 233.063 picogram per milliliter (pg/mL) | Standard Deviation 46.086 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 675.010 picogram per milliliter (pg/mL) | Standard Deviation 96.1891 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 951.438 picogram per milliliter (pg/mL) | Standard Deviation 207.381 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 859.977 picogram per milliliter (pg/mL) | Standard Deviation 160.9109 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 277.878 picogram per milliliter (pg/mL) | Standard Deviation 57.0774 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 155.707 picogram per milliliter (pg/mL) | Standard Deviation 37.52 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 375.772 picogram per milliliter (pg/mL) | Standard Deviation 72.3014 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 9.123 picogram per milliliter (pg/mL) | Standard Deviation 22.3475 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 758.747 picogram per milliliter (pg/mL) | Standard Deviation 238.7338 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 489.127 picogram per milliliter (pg/mL) | Standard Deviation 72.4588 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 668.387 picogram per milliliter (pg/mL) | Standard Deviation 181.7359 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 807.632 picogram per milliliter (pg/mL) | Standard Deviation 193.109 |
| Cohort 2: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 545.100 picogram per milliliter (pg/mL) | Standard Deviation 151.8562 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 677.693 picogram per milliliter (pg/mL) | Standard Deviation 194.5259 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 134.788 picogram per milliliter (pg/mL) | Standard Deviation 39.9181 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 248.055 picogram per milliliter (pg/mL) | Standard Deviation 79.1963 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 467.965 picogram per milliliter (pg/mL) | Standard Deviation 173.5354 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 361.720 picogram per milliliter (pg/mL) | Standard Deviation 113.4442 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 493.835 picogram per milliliter (pg/mL) | Standard Deviation 113.3446 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 565.527 picogram per milliliter (pg/mL) | Standard Deviation 137.2089 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 781.040 picogram per milliliter (pg/mL) | Standard Deviation 167.7037 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 828.695 picogram per milliliter (pg/mL) | Standard Deviation 271.3573 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 379.647 picogram per milliliter (pg/mL) | Standard Deviation 189.7192 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 617.653 picogram per milliliter (pg/mL) | Standard Deviation 192.0337 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 3: MT203 300 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 14.857 picogram per milliliter (pg/mL) | Standard Deviation 23.0308 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: Placebo | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 56 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 28 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 70 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 240 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 336 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 72 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 120 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 42 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 24 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 21 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 168 Hours | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | Baseline | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
| Cohort 4: MT203 150 mg | Plasma Total Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) Concentration | 84 Days | 0.000 picogram per milliliter (pg/mL) | Standard Deviation 0 |
Secondary
Terminal Elimination Half-Life (T1/2) of MT203
Time frame: Predose and at multiple time points (up to 84 days) post-dose
Population: The pharmacokinetic analysis set as defined as all participants who received the study medication without any major protocol deviations, and met the minimum procedure specified in the study protocol and had evaluable pharmacokinetic data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1-3: Placebo | Terminal Elimination Half-Life (T1/2) of MT203 | 23.75 day |
| Cohort 1: MT203 80 mg | Terminal Elimination Half-Life (T1/2) of MT203 | 26.20 day |
| Cohort 2: MT203 150 mg | Terminal Elimination Half-Life (T1/2) of MT203 | 26.15 day |
| Cohort 3: MT203 300 mg | Terminal Elimination Half-Life (T1/2) of MT203 | 32.60 day |