Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, MT203, Human IgG1 monoclonal antibody, GM-CSF monoclonal antibody
Brief summary
The purpose of this trial is primarily to investigate the safety and tolerability of repeated subcutaneous injections of MT203 in patients with mild to moderate rheumatoid arthritis. Furthermore, the amount of MT203 in the blood will be measured and it will be investigated how the body responds to MT203 treatment and if MT203 is effective in the treatment of rheumatoid arthritis.
Detailed description
The trial medication will be administered at 2 dose levels as subcutaneous injections. Each patient will receive three injections in total. The trial duration consists of a screening period (28 - 2 days prior to the first injection) and a treatment and observation period (4 months). The trial requires approximately 20 visits at the study site.
Interventions
DRUGnamilumab (MT203)
administered three times, subcutaneous in the abdomen
DRUGPlacebo
administered three times, subcutaneous in the abdomen
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Out-patients with active rheumatoid arthritis (RA), according to the ACR 1987 revised criteria, with low to moderate disease activity (DAS28-ESR ≥ 2.6 and ≤ 5.1) 2. Patients must be on stable doses of methotrexate (MTX) ≥ 7.5 and ≤ 25 mg/week for at least 12 weeks before the first injection, with appropriate folic acid supplementation 3. Age ≥ 18 years at Screening 4. Body weight at least 50 kg at Screening; BMI: ≥ 18.0 and ≤ 30.0 kg/m2 at Screening 5. Negative tuberculosis test at Screening 6. Heterosexually active male and female patients of childbearing potential are obliged to follow whatever contraceptive and / or breastfeeding restrictions may be required for their concomitant medication(s), including methotrexate. In addition, heterosexually active male and female patients of childbearing potential are required to use effective double-method contraception (one hormonal contraceptive or intrauterine device and one other additional contraceptive method) for 1 month before the first administration of the IMP, during the course of the trial, and for 6 month after the last injection of MT203. No special requirements are made for female patients proven to be post-menopausal (at least 2 years after last menstrual period and FSH ≥ 40IU/L), surgically sterilized or hysterectomized. Likewise no special requirements for heterosexually active male who are surgical sterilized. Pregnant or lactating female patients have to be excluded.
Exclusion criteria
1. Participation in another clinical trial or previous dosing in this trial 2. Use of specified medications within certain timeframes or use of certain comedications 3. History or presence of specified diseases 4. Drug abuse 5. Certain laboratory parameters outside a specified range 6. Donation of blood 7. Relevant decrease in lung function 8. Infections, frequent or chronic infections, herpes zoster 9. Females: positive pregnancy test 10. Presence of history of tuberculosis 11. History of malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Clinical Laboratory Results | From Day 1 Up to Day 118 | Blood was collected for Haematology, Chemistry and Coagulation. Urine was collected for Urinalysis. Alert values for laboratory results include the following: Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl-transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin (TBil): \> 3 times upper limit of normal (ULN). Creatinine and Glucose: \> 2 times ULN. Potassium \> 6.0 or \< 3.0 mmol/L. Haemoglobin: Male \< 8.0 ;Female \< 7.0 g/dL. Erythrocytes :Male \< 3.5 x 10\^12/L or \> 7 x 10\^12/L;Female \< 3.0 x 10\^12/L or \> 6.5 x 10\^12/L. White Blood Cells (WBC): \< 2.8 x10\^9/L or \> 16.0 x 10\^9/L. Eosinophils \> 20 % of cells in the WBC differential. Platelet Count \< 75 x 10\^9/L or 600 x 10\^9/L. No alert values were identified for Coagulation or Urinalysis. |
| Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | From Day 1 Up to Day 118 | Alert values for ECG were: Heart rate \< 35 bpm or \> 120 bpm, QTc acc. to Bazett (absolute value)\> 500 ms or QTc acc. to Bazett (increase versus Baseline (pre-treatment). |
| Number of Participants With Clinically Significant Vital Signs | From Day 1 Up to Day 118 | Vital signs included Systolic Blood Pressure (BP), Diastolic BP, body temperature, heart rate. Alert values were: BP systolic \> 170 mmHg or \< 85 mmHg, BP diastolic \> 105 mmHg, Difference BP systolic vs. Baseline (pre-treatment) \> 40 mmHg or Pulse rate \< 35 bpm or \> 120 beats per minute (bpm). |
| Number of Participants With Clinically Significant Pulmonary Function Tests | From Day 1 Up to Day 118 | Pulmonary function was determined by forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak flow. |
| Number of Participants With Clinically Significant Physical Examination Findings | From Day 1 Up to Day 118 | The physical examination included body system assessments: eyes, head and neck (including thyroid), ears, nose and throat, lymph nodes, cardiovascular, lungs, mammae, abdomen (liver, spleen), genitals, limbs, central and peripheral nervous system, musculoskeletal system, skin & nails, mucosae. The Investigator classified abnormal findings as either clinically significant or not clinically significant. |
| Number of Participants Reporting One or More Treatment Emergent Adverse Events | From Day 1 Up to Day 118 | An Adverse Event (AE) was 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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Days 1, 15 and 29 Pre-dose | — |
| Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118 | MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex. The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample. A positive change from Baseline indicated improvement. |
| Change From Baseline in MT203/GM-CSF Complexes in Plasma | Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, EOT Up to Day 118 | MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex. The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample. A positive change from Baseline indicated improvement. |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203 | Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose) | Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax |
| Percentage of Participants With American College of Rheumatology (ACR 20) Response | Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118 | ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate. |
| Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118 | Ritchie articular index (RAI); a joint count that grades the tenderness of 26 joints on a scale of 0-3); the number of swollen joints from 44 joints (swollen44); ESR in mm/hour after 1 hour and the patient's global disease activity on a Visual Analogue Scale (VAS) of 100 mm (0=no disease activity to right end of the line 100=maximum disease activity) were used to calculate DAS44-ESR using the following formula: DAS44-ESR = 0.54\*sqrt(RAI) + 0.065\*(swollen44) + 0.33\*ln(ESR) + 0.0072\*VAS. Lower numbers were better. A negative change from Baseline indicated improvement. |
| Number of Participants With Anti-MT203 Antibodies | From Day 1 Up to Day 118 | Serum samples were tested for the presence of anti-MT203 antibodies by a bridging Electro-chemi-luminescent assay (ECL-assay). |
| Cmax: Maximum Observed Plasma Concentration for MT203 | Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose) | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. |
| AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203 | Day 29 (Pre-dose and 2 and 6 hours post-dose) | Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval. |
| AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203 | Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose) | AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]). |
| AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203 | Day 29 (Pre-dose and 2 and 6 hours post-dose) | AUC(0-inf) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau\]), where tau is the length of the dosing interval in this study). |
| Terminal Phase Elimination Half-life (T1/2) for MT203 | Day 29 (Pre-dose and 2 and 6 hours post-dose) | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. |
Countries
Bulgaria, Netherlands
Participant flow
Recruitment details
Participants took part in the study at 10 investigative sites in Bulgaria, Netherlands and Spain from 09 March 2011 to 08 August 2013.
Pre-assignment details
Participants with a diagnosis of mild or moderate rheumatoid arthritis were enrolled into 1 of 3 treatment groups namilumab (MT203) 150mg, namilumab 300 mg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Namilumab 150 mg Namilumab (MT203) 150 mg (low dose), subcutaneous (SC) injection, on Days 1, 15 and 29. | 8 |
| Namilumab 300 mg Namilumab (MT203) 300 mg (high dose), SC injection, on Days 1, 15 and 29. | 7 |
| Placebo Namilumab-matching placebo, SC injection, on Days 1, 15 and 29. | 9 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Other | 0 | 1 | 0 |
| Overall Study | Withdrawal of Patient | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Namilumab 150 mg | Namilumab 300 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 6.95 | 56.6 years STANDARD_DEVIATION 15.28 | 53.4 years STANDARD_DEVIATION 11.05 | 55.9 years STANDARD_DEVIATION 11.05 |
| Body Mass Index (BMI) | 24.69 kg/m^2 STANDARD_DEVIATION 2.471 | 28.30 kg/m^2 STANDARD_DEVIATION 1.778 | 27.37 kg/m^2 STANDARD_DEVIATION 2.246 | 26.75 kg/m^2 STANDARD_DEVIATION 2.607 |
| Disease Activity Score 28-Erythrocyte Sedimentation Rate (DAS28-ESR) Score | 4.70 score on a scale STANDARD_DEVIATION 0.542 | 4.66 score on a scale STANDARD_DEVIATION 0.544 | 4.60 score on a scale STANDARD_DEVIATION 0.512 | 4.65 score on a scale STANDARD_DEVIATION 0.51 |
| Height | 166.21 cm STANDARD_DEVIATION 8.605 | 168.57 cm STANDARD_DEVIATION 6.321 | 168.44 cm STANDARD_DEVIATION 5.126 | 167.74 cm STANDARD_DEVIATION 6.581 |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 7 participants | 7 participants | 9 participants | 23 participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 3 Participants | 7 Participants |
| Weight | 68.13 kg STANDARD_DEVIATION 7.14 | 80.44 kg STANDARD_DEVIATION 7.305 | 77.80 kg STANDARD_DEVIATION 8.617 | 75.35 kg STANDARD_DEVIATION 9.147 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 8 | 4 / 7 | 5 / 9 |
| serious Total, serious adverse events | 2 / 8 | 0 / 7 | 0 / 9 |
Outcome results
Primary
Number of Participants Reporting One or More Treatment Emergent Adverse Events
An Adverse Event (AE) was 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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants Reporting One or More Treatment Emergent Adverse Events | 5 participants |
| Namilumab 300 mg | Number of Participants Reporting One or More Treatment Emergent Adverse Events | 4 participants |
| Placebo | Number of Participants Reporting One or More Treatment Emergent Adverse Events | 5 participants |
Primary
Number of Participants With Clinically Significant Clinical Laboratory Results
Blood was collected for Haematology, Chemistry and Coagulation. Urine was collected for Urinalysis. Alert values for laboratory results include the following: Aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), gamma-glutamyl-transpeptidase (GGT), alkaline phosphatase (AP), total bilirubin (TBil): \> 3 times upper limit of normal (ULN). Creatinine and Glucose: \> 2 times ULN. Potassium \> 6.0 or \< 3.0 mmol/L. Haemoglobin: Male \< 8.0 ;Female \< 7.0 g/dL. Erythrocytes :Male \< 3.5 x 10\^12/L or \> 7 x 10\^12/L;Female \< 3.0 x 10\^12/L or \> 6.5 x 10\^12/L. White Blood Cells (WBC): \< 2.8 x10\^9/L or \> 16.0 x 10\^9/L. Eosinophils \> 20 % of cells in the WBC differential. Platelet Count \< 75 x 10\^9/L or 600 x 10\^9/L. No alert values were identified for Coagulation or Urinalysis.
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Namilumab 150 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Haematology | 3 participants |
| Namilumab 150 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Chemistry | 1 participants |
| Namilumab 150 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Coagulation | 0 participants |
| Namilumab 150 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Urine | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Urine | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Haematology | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Coagulation | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Clinical Laboratory Results | Chemistry | 1 participants |
| Placebo | Number of Participants With Clinically Significant Clinical Laboratory Results | Urine | 0 participants |
| Placebo | Number of Participants With Clinically Significant Clinical Laboratory Results | Chemistry | 1 participants |
| Placebo | Number of Participants With Clinically Significant Clinical Laboratory Results | Coagulation | 0 participants |
| Placebo | Number of Participants With Clinically Significant Clinical Laboratory Results | Haematology | 1 participants |
Primary
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
Alert values for ECG were: Heart rate \< 35 bpm or \> 120 bpm, QTc acc. to Bazett (absolute value)\> 500 ms or QTc acc. to Bazett (increase versus Baseline (pre-treatment).
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 1 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 participants |
| Placebo | Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings | 0 participants |
Primary
Number of Participants With Clinically Significant Physical Examination Findings
The physical examination included body system assessments: eyes, head and neck (including thyroid), ears, nose and throat, lymph nodes, cardiovascular, lungs, mammae, abdomen (liver, spleen), genitals, limbs, central and peripheral nervous system, musculoskeletal system, skin & nails, mucosae. The Investigator classified abnormal findings as either clinically significant or not clinically significant.
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants With Clinically Significant Physical Examination Findings | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Physical Examination Findings | 0 participants |
| Placebo | Number of Participants With Clinically Significant Physical Examination Findings | 0 participants |
Primary
Number of Participants With Clinically Significant Pulmonary Function Tests
Pulmonary function was determined by forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak flow.
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants With Clinically Significant Pulmonary Function Tests | 0 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Pulmonary Function Tests | 0 participants |
| Placebo | Number of Participants With Clinically Significant Pulmonary Function Tests | 1 participants |
Primary
Number of Participants With Clinically Significant Vital Signs
Vital signs included Systolic Blood Pressure (BP), Diastolic BP, body temperature, heart rate. Alert values were: BP systolic \> 170 mmHg or \< 85 mmHg, BP diastolic \> 105 mmHg, Difference BP systolic vs. Baseline (pre-treatment) \> 40 mmHg or Pulse rate \< 35 bpm or \> 120 beats per minute (bpm).
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants With Clinically Significant Vital Signs | 3 participants |
| Namilumab 300 mg | Number of Participants With Clinically Significant Vital Signs | 0 participants |
| Placebo | Number of Participants With Clinically Significant Vital Signs | 0 participants |
Secondary
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203
AUC(0-inf) is measure of area under the curve over the dosing interval (tau) (AUC(0-tau\]), where tau is the length of the dosing interval in this study).
Time frame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated. Method of Dispersion is the 68% range.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Namilumab 150 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203 | 832.8 day*μg/mL |
| Namilumab 300 mg | AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MT203 | 1861 day*μg/mL |
Secondary
AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203
Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.
Time frame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated. Method of Dispersion is the 68% range.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Namilumab 150 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203 | 318.5 day*μg/mL |
| Namilumab 300 mg | AUC(0-tau): Area Under the Plasma Concentration-time Curve From Time 0 to Time Tau Over the Dosing Interval for MT203 | 591.9 day*μg/mL |
Secondary
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203
AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC\[0-tlqc\]).
Time frame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated. Method of Dispersion is the 68% range.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Namilumab 150 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203 | Day 1 | 144.9 day*μg/mL |
| Namilumab 150 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203 | Day 29 | 786.8 day*μg/mL |
| Namilumab 300 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203 | Day 1 | 210.9 day*μg/mL |
| Namilumab 300 mg | AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MT203 | Day 29 | 1696 day*μg/mL |
Secondary
Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma
MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex. The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample. A positive change from Baseline indicated improvement.
Time frame: Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, End of trial (EOT) Up to Day 118
Population: All randomized participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 99 (n=7, 6, 7) | 9.11 pg/mL | Standard Deviation 11.113 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 43 (n=7, 7, 8) | 40.04 pg/mL | Standard Deviation 18.838 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 29 (n=7, 7, 8) | 31.59 pg/mL | Standard Deviation 13.323 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 6 (n=6, 7, 9) | 3.00 pg/mL | Standard Deviation 3.286 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 35 (n=7, 7, 7) | 33.29 pg/mL | Standard Deviation 20.203 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 30 (n=6, 7, 8) | 40.68 pg/mL | Standard Deviation 24.908 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 2 (n=7, 7, 9) | 0.00 pg/mL | Standard Deviation 0 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 4 (n=6, 7, 9) | 3.00 pg/mL | Standard Deviation 3.286 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 71 (n=5, 6, 8) | 31.48 pg/mL | Standard Deviation 21.759 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 8 (n=6, 7, 9) | 7.78 pg/mL | Standard Deviation 10.33 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | EOT (n=7, 6, 9) | 3.87 pg/mL | Standard Deviation 7.919 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 56 (n=7, 6, 8) | 38.34 pg/mL | Standard Deviation 20.33 |
| Namilumab 150 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 15 (n=7, 7, 9) | 16.86 pg/mL | Standard Deviation 8.825 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 30 (n=6, 7, 8) | 22.11 pg/mL | Standard Deviation 16.954 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 2 (n=7, 7, 9) | -0.86 pg/mL | Standard Deviation 2.268 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 4 (n=6, 7, 9) | 0.86 pg/mL | Standard Deviation 4.14 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 6 (n=6, 7, 9) | 2.57 pg/mL | Standard Deviation 3.207 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 8 (n=6, 7, 9) | 4.29 pg/mL | Standard Deviation 2.928 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 15 (n=7, 7, 9) | 8.61 pg/mL | Standard Deviation 8.978 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 29 (n=7, 7, 8) | 15.14 pg/mL | Standard Deviation 6.69 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 35 (n=7, 7, 7) | 25.71 pg/mL | Standard Deviation 16.261 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 43 (n=7, 7, 8) | 28.10 pg/mL | Standard Deviation 15.013 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 56 (n=7, 6, 8) | 32.32 pg/mL | Standard Deviation 14.337 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 71 (n=5, 6, 8) | 35.02 pg/mL | Standard Deviation 12.402 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 99 (n=7, 6, 7) | 23.77 pg/mL | Standard Deviation 8.881 |
| Namilumab 300 mg | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | EOT (n=7, 6, 9) | 17.38 pg/mL | Standard Deviation 10.745 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 43 (n=7, 7, 8) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 8 (n=6, 7, 9) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 99 (n=7, 6, 7) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 56 (n=7, 6, 8) | 0.75 pg/mL | Standard Deviation 2.121 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 6 (n=6, 7, 9) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 2 (n=7, 7, 9) | 0.67 pg/mL | Standard Deviation 2 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 71 (n=5, 6, 8) | 0.75 pg/mL | Standard Deviation 2.121 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 30 (n=6, 7, 8) | 0.75 pg/mL | Standard Deviation 2.121 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 29 (n=7, 7, 8) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 4 (n=6, 7, 9) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 35 (n=7, 7, 7) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | Day 15 (n=7, 7, 9) | 0.00 pg/mL | Standard Deviation 0 |
| Placebo | Change From Baseline in Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Plasma | EOT (n=7, 6, 9) | 0.67 pg/mL | Standard Deviation 2 |
Secondary
Change From Baseline in MT203/GM-CSF Complexes in Plasma
MT203/GM-CSF complexes were analysed using a procedure that quantified GM-CSF after dissociation from the complex. The determined concentrations corresponded to the amount of total (free and complexed) GM-CSF in the plasma sample. A positive change from Baseline indicated improvement.
Time frame: Baseline and Days 2, 4, 6, 8 15, 29, 30, 35, 43, 56, 71, 99, EOT Up to Day 118
Population: All randomized participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 99 (n=8, 6, 8) | 462.6 pg/mL | Standard Deviation 275.4 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 43 (n=8, 7, 8) | 2213.0 pg/mL | Standard Deviation 744.37 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 29 (n=8, 7, 8) | 1566.9 pg/mL | Standard Deviation 391.8 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 6 (n=8, 7, 9) | 381.6 pg/mL | Standard Deviation 152.52 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 35 (n=8, 7, 8) | 1796.9 pg/mL | Standard Deviation 560.58 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 30 (n=8, 7, 8) | 1653.5 pg/mL | Standard Deviation 498.31 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 2 (n=8, 7, 9) | 30.9 pg/mL | Standard Deviation 63.92 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 4 (n=8, 7, 9) | 210.6 pg/mL | Standard Deviation 183.16 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 71 (n=8, 6, 8) | 1299.6 pg/mL | Standard Deviation 313.2 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 8 (n=8, 7, 9) | 448.0 pg/mL | Standard Deviation 110.76 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | EOT (n=8, 6, 9) | 310.4 pg/mL | Standard Deviation 144.03 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 56 (n=8, 6, 8) | 2009.0 pg/mL | Standard Deviation 614.92 |
| Namilumab 150 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 15 (n=8, 7, 9) | 1021.0 pg/mL | Standard Deviation 353.03 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 30 (n=8, 7, 8) | 1834.9 pg/mL | Standard Deviation 178.71 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 2 (n=8, 7, 9) | 12.7 pg/mL | Standard Deviation 16.25 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 4 (n=8, 7, 9) | 186.1 pg/mL | Standard Deviation 100.15 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 6 (n=8, 7, 9) | 334.6 pg/mL | Standard Deviation 89.19 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 8 (n=8, 7, 9) | 534.1 pg/mL | Standard Deviation 80.58 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 15 (n=8, 7, 9) | 1055.0 pg/mL | Standard Deviation 124.65 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 29 (n=8, 7, 8) | 1805.4 pg/mL | Standard Deviation 150.43 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 35 (n=8, 7, 8) | 2052.9 pg/mL | Standard Deviation 294.95 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 43 (n=8, 7, 8) | 2290.6 pg/mL | Standard Deviation 282.35 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 56 (n=8, 6, 8) | 2457.2 pg/mL | Standard Deviation 466.01 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 71 (n=8, 6, 8) | 2312.2 pg/mL | Standard Deviation 492.5 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 99 (n=8, 6, 8) | 1753.5 pg/mL | Standard Deviation 351.34 |
| Namilumab 300 mg | Change From Baseline in MT203/GM-CSF Complexes in Plasma | EOT (n=8, 6, 9) | 1310.8 pg/mL | Standard Deviation 460.45 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 43 (n=8, 7, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 8 (n=8, 7, 9) | -1.3 pg/mL | Standard Deviation 4 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 99 (n=8, 6, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 56 (n=8, 6, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 6 (n=8, 7, 9) | -1.3 pg/mL | Standard Deviation 4 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 2 (n=8, 7, 9) | -0.2 pg/mL | Standard Deviation 0.67 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 71 (n=8, 6, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 30 (n=8, 7, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 29 (n=8, 7, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 4 (n=8, 7, 9) | -0.6 pg/mL | Standard Deviation 1.67 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 35 (n=8, 7, 8) | -4.4 pg/mL | Standard Deviation 12.37 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | Day 15 (n=8, 7, 9) | -3.9 pg/mL | Standard Deviation 11.67 |
| Placebo | Change From Baseline in MT203/GM-CSF Complexes in Plasma | EOT (n=8, 6, 9) | -3.9 pg/mL | Standard Deviation 11.67 |
Secondary
Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR)
Ritchie articular index (RAI); a joint count that grades the tenderness of 26 joints on a scale of 0-3); the number of swollen joints from 44 joints (swollen44); ESR in mm/hour after 1 hour and the patient's global disease activity on a Visual Analogue Scale (VAS) of 100 mm (0=no disease activity to right end of the line 100=maximum disease activity) were used to calculate DAS44-ESR using the following formula: DAS44-ESR = 0.54\*sqrt(RAI) + 0.065\*(swollen44) + 0.33\*ln(ESR) + 0.0072\*VAS. Lower numbers were better. A negative change from Baseline indicated improvement.
Time frame: Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
Population: All randomized participants with data available for analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 27 (n=8, 7, 9) | -0.798 score on a scale | Standard Deviation 0.6432 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 71 (n=7, 6, 7) | -0.853 score on a scale | Standard Deviation 0.4461 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 56 (n=8, 6, 8) | -1.002 score on a scale | Standard Deviation 0.9624 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 13 (n=8, 7, 9) | -0.473 score on a scale | Standard Deviation 0.7412 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | EOT (n=8, 6, 9) | -0.591 score on a scale | Standard Deviation 0.5664 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 99 (n=8, 6, 8) | -0.678 score on a scale | Standard Deviation 0.4345 |
| Namilumab 150 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 43 (n=8, 7, 8) | -0.873 score on a scale | Standard Deviation 0.6064 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 56 (n=8, 6, 8) | -1.190 score on a scale | Standard Deviation 0.8217 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 13 (n=8, 7, 9) | -0.310 score on a scale | Standard Deviation 0.5369 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 27 (n=8, 7, 9) | -0.995 score on a scale | Standard Deviation 0.7094 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 43 (n=8, 7, 8) | -0.852 score on a scale | Standard Deviation 0.8223 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 71 (n=7, 6, 7) | -0.980 score on a scale | Standard Deviation 0.7478 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 99 (n=8, 6, 8) | -0.914 score on a scale | Standard Deviation 0.7782 |
| Namilumab 300 mg | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | EOT (n=8, 6, 9) | -0.974 score on a scale | Standard Deviation 0.5992 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 71 (n=7, 6, 7) | -1.134 score on a scale | Standard Deviation 1.124 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 27 (n=8, 7, 9) | -0.383 score on a scale | Standard Deviation 0.7425 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | EOT (n=8, 6, 9) | -1.138 score on a scale | Standard Deviation 0.9667 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 99 (n=8, 6, 8) | -1.025 score on a scale | Standard Deviation 0.8533 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 56 (n=8, 6, 8) | -1.184 score on a scale | Standard Deviation 1.0178 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 43 (n=8, 7, 8) | -0.469 score on a scale | Standard Deviation 0.6585 |
| Placebo | Change From Baseline in the Disease Activity Score 44-Erythrocyte Sedimentation Rate (DAS44-ESR) | Day 13 (n=8, 7, 9) | -0.344 score on a scale | Standard Deviation 0.6491 |
Secondary
Cmax: Maximum Observed Plasma Concentration for MT203
Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time frame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated. Method of Dispersion is the 68% range.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Namilumab 150 mg | Cmax: Maximum Observed Plasma Concentration for MT203 | Day 1 | 13.41 μg/mL |
| Namilumab 150 mg | Cmax: Maximum Observed Plasma Concentration for MT203 | Day 29 | 27.14 μg/mL |
| Namilumab 300 mg | Cmax: Maximum Observed Plasma Concentration for MT203 | Day 1 | 18.76 μg/mL |
| Namilumab 300 mg | Cmax: Maximum Observed Plasma Concentration for MT203 | Day 29 | 49.99 μg/mL |
Secondary
Ctrough: Maximum Observed Plasma Concentration Pre-Dose
Time frame: Days 1, 15 and 29 Pre-dose
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated. Method of Dispersion is the 68% range.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Namilumab 150 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 1 | 9.232 μg/mL |
| Namilumab 150 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 15 | 15.53 μg/mL |
| Namilumab 150 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 29 | 20.27 μg/mL |
| Namilumab 300 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 1 | 14.56 μg/mL |
| Namilumab 300 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 15 | 27.28 μg/mL |
| Namilumab 300 mg | Ctrough: Maximum Observed Plasma Concentration Pre-Dose | Day 29 | 36.88 μg/mL |
Secondary
Number of Participants With Anti-MT203 Antibodies
Serum samples were tested for the presence of anti-MT203 antibodies by a bridging Electro-chemi-luminescent assay (ECL-assay).
Time frame: From Day 1 Up to Day 118
Population: Safety population included all randomized participants who received study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Namilumab 150 mg | Number of Participants With Anti-MT203 Antibodies | 0 participants |
| Namilumab 300 mg | Number of Participants With Anti-MT203 Antibodies | 0 participants |
| Placebo | Number of Participants With Anti-MT203 Antibodies | 0 participants |
Secondary
Percentage of Participants With American College of Rheumatology (ACR 20) Response
ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant Erythrocyte Sedimentation Rate.
Time frame: Baseline and Days 13,27,43,56,71,99 and EOT Up to Day 118
Population: All randomized participants with data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 27 | 50.0 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 71 | 62.5 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 56 | 50.0 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 13 | 50.0 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | EOT | 37.5 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 99 | 50.0 percentage of participants |
| Namilumab 150 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 43 | 37.5 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 56 | 57.1 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 13 | 14.3 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 27 | 57.1 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 43 | 71.4 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 71 | 57.1 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 99 | 42.9 percentage of participants |
| Namilumab 300 mg | Percentage of Participants With American College of Rheumatology (ACR 20) Response | EOT | 57.1 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 71 | 44.4 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 27 | 33.3 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | EOT | 44.4 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 99 | 44.4 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 56 | 55.6 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 43 | 44.4 percentage of participants |
| Placebo | Percentage of Participants With American College of Rheumatology (ACR 20) Response | Day 13 | 11.1 percentage of participants |
Secondary
Terminal Phase Elimination Half-life (T1/2) for MT203
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: Day 29 (Pre-dose and 2 and 6 hours post-dose)
Population: PK Analysis set included all 15 participants who were exposed to study drug for whom any PK parameters could be calculated.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Namilumab 150 mg | Terminal Phase Elimination Half-life (T1/2) for MT203 | 21.26 days |
| Namilumab 300 mg | Terminal Phase Elimination Half-life (T1/2) for MT203 | 23.68 days |
Secondary
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203
Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax
Time frame: Day 1 and 29 (Pre-dose and 2 and 6 hours post-dose)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Namilumab 150 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203 | Day 1 | 4.98 days |
| Namilumab 150 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203 | Day 29 | 4.97 days |
| Namilumab 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203 | Day 1 | 5.95 days |
| Namilumab 300 mg | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MT203 | Day 29 | 6.00 days |