A Trial to Evaluate the Safety and Tolerability of Namilumab (MT203) in Patients With Mild to Moderate Rheumatoid Arthritis

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.

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).

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).

Pulmonary function was determined by forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak flow.

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.

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.

Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax

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-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) 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).

Area under the plasma concentration-time curve during a dosing interval, where tau is the length of the dosing interval.

Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the 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.

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.

Serum samples were tested for the presence of anti-MT203 antibodies by a bridging Electro-chemi-luminescent assay (ECL-assay).

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.

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.