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

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)

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)

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)

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)

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.

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.