A Study to Evaluate the Safety and Efficacy of SM03 in Patients With Rheumatoid Arthritis Receiving Methotrexate

실험적: SM03 600 mg*2

SM03: 600 mg intravenous (IV) on week 0,2, and week 12,14; placebo: 600 mg intravenous (IV) on week 4 and16; Methotrexate: 7.5-20 mg/wk oral.

의약품: 에스엠03

SM03: 600mg 정맥주사(IV)

의약품: 위약

위약: 600mg 정맥내(IV)

의약품: Methotrexate

methotrexate: 7.5-20 mg/week oral

실험적: SM03 600 mg*3

SM03: 600 mg intravenous (IV) on week 0,2, 4, and week 12,14,16; Methotrexate: 7.5-20 mg/wk oral.

의약품: 에스엠03

SM03: 600mg 정맥주사(IV)

의약품: Methotrexate

methotrexate: 7.5-20 mg/week oral

위약 비교기: placebo*3

placebo: 600 mg intravenous (IV) on week 0,2, 4, and week 12,14,16; Methotrexate: 7.5-20 mg/wk oral.

의약품: 위약

위약: 600mg 정맥내(IV)

의약품: Methotrexate

methotrexate: 7.5-20 mg/week oral

Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24

To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements:

• Physician's global assessment of disease activity (assessed using a 10 cm Visual Analog Scale [VAS]);
• Patient's global assessment of disease activity (assessed using a 10 cm VAS);
• Patient's assessment of pain (assessed using a 10 cm VAS);
• Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
• Acute phase reactant: C-reactive protein (CRP)

Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 4,8,12, 16

To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements:

• Physician's global assessment of disease activity (assessed using a 10 cm Visual Analog Scale [VAS]);
• Patient's global assessment of disease activity (assessed using a 10 cm VAS);
• Patient's assessment of pain (assessed using a 10 cm VAS);
• Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
• Acute phase reactant: C-reactive protein (CRP)

Percentage of Participants With an ACR50 Response at Week 24

To achieve an ACR50 required at least a 50% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 50% improvement in three of the following five additional measurements:

• Physician's global assessment of disease activity (assessed using a 10 cm Visual Analog Scale [VAS]);
• Patient's global assessment of disease activity (assessed using a 10 cm VAS);
• Patient's assessment of pain (assessed using a 10 cm VAS);
• Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
• Acute phase reactant: C-reactive protein (CRP)

Percentage of Participants With an ACR70 Response at Week 24

To achieve an ACR70 required at least a 70% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 70% improvement in three of the following five additional measurements:

• Physician's global assessment of disease activity (assessed using a 10 cm Visual Analog Scale [VAS]);
• Patient's global assessment of disease activity (assessed using a 10 cm VAS);
• Patient's assessment of pain (assessed using a 10 cm VAS);
• Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3);
• Acute phase reactant: C-reactive protein (CRP)

Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24

The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables:

• The number of swollen and tender joints assessed using the 28-joint count;
• Erythrocyte sedimentation rate (ESR);
• Patient's global assessment of disease activity measured on a 10 cm visual analog scale.

The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. Remission is achieved by a DAS28 lower than 2.6.

Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24

A EULAR response reflects an improvement in disease activity and an attainment of a lower degree of disease activity based on the DAS28 score. The DAS28 score ranges from 0-10, with higher scores indicating more disease activity.

A Good Response is defined as an improvement (decrease) in the DAS28 of more than 1.2 compared with Baseline and attainment of a DAS28 score of less than or equal to 3.2.

A Moderate Response is defined as either:

an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 from Baseline and attainment of a DAS28 score of less than or equal to 5.1 or, an improvement (decrease) in the DAS28 of more than 1.2 from Baseline and attainment of a DAS28 score of greater than 3.2.

No Response is defined as either an improvement (decrease) in the DAS28 of less than or equal to 0.6, or an improvement (decrease) in the DAS28 of greater than 0.6 and less than or equal to 1.2 and attainment of a DAS28 of more than 5.1.

Percentage of Participants With Adverse Events

Percentage of participants who reported an AE or SAE, a drug-related AE, who had an acute infusion reaction, an AE leading to study drug discontinuation, with an infection or serious infection, or who died.