Comparative Efficacy and Safety Study of GP2015 and Enbrel® in Patients With Rheumatoid Arthritis

Frequency of participants with injection site reactions in GP2015 and Enbrel

Frequency of patients having anti-drug antibody (ADA) during 24 weeks (Treatment Period 1) using 1% false positive rate

DAS28-CRP is a disease activity score and defined in primary outcome measure. DAS28-ESR is the DAS28 erythrocyte sedimentation rate score.

DAS28-CRP and DAS28-ESR:

1. best is 0,
2. < 2.6 - remission,
3. ≥ 2.6 to ≤ 3.2 - low disease activity
4. > 3.2 to ≤ 5.1 - moderate disease activity
5. > 5.1 - high disease activity

DAS28-ESR = 0.56 * sqrt(tender28) + 0.28* sqrt(swollen28) + 0.7 * ln(ESR) + 0.014 * GDA where • tender28 and swollen28 are the number of tender and swollen joints as assessed using 28-joint count • CRP is C-reactive protein (mg/l) • ESR is erythrocyte sedimentation rate (mm/h) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm

Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28 ≤ 3.2 and DAS28 improvement from Baseline > 1.2) and moderate response (defined as DAS28 ≤ 3.2 and DAS28 improvement > 0.6 and ≤ 1.2, or DAS28 > 3.2 and ≤ 5.1 and DAS28 improvement > 0.6 or DAS28 > 5.1 but DAS28 improvement > 1.2) ;

% patients in DAS28-ESR categories up to week 24

Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joints/swollen joints ≤ 1 and CRP (mg/dL) ≤ 1 and patient global assessment (1-10) ≤ 1) at Weeks 4, 12 and 24;

ACR20 response was defined if a patient fulfilled all 3 criteria below:

• 20% improvement in tender 68 joint-count
• 20% improvement in swollen 68 joint-count;

And 20% improvement in at least 3 of the following 5 measures:

• Patient's assessment of RA pain (visual analogue scale (VAS) 100 mm),
• Patient's global assessment of disease activity (VAS 100 mm),
• Physician's global assessment of disease activity (VAS 100 mm),
• Patient self-assessed disability (HAQ score),
• Acute phase reactant (CRP or ESR). ACR50 and ACR70 responses were defined as ACR20 response replacing "20% improvement" by "50% improvement" and "70% improvement", respectively.

ACR-N (American College of Rheumatology percentage of improvement): negative is worsening, positive (up to 100) is an improvement.

ACR-N is a single number that characterizes the percentage of improvement from Baseline that a patient has experienced in analogy to ACR20 described above. ACR-N of X (such as 38) means that the patient had achieved an improvement of at least X% (such as 38%) in tender and swollen joints, and an improvement of at least X% (such as 38%) in 3 of the 5 other parameters mentioned above.

Proportion of patients in each disease activity category as defined by the Simplified Disease Activity Index (SDAI): high disease activity, SDAI > 26, moderate disease activity, SDAI > 11 to ≤ 26, low disease activity, SDAI > 3.3 to ≤ 11, and remission, SDAI ≤ 3.3 at Weeks 4, 12 and 24; SDAI and CDAI are measures of disease activity in RA. The scores were calculated by numerical summation of the number of tender and swollen joints (using the 28-joint count), and the patient's and physician's global assessment of disease activity.

Proportion of patients in each disease activity category as defined by the Clinical Disease Activity Index (CDAI): high disease activity, CDAI > 22, moderate disease activity, CDAI > 10 to ≤ 22, low disease activity, CDAI > 2.8 to ≤ 10, and remission, CDAI ≤ 2.8 at Weeks 4, 12 and 24; SDAI and CDAI are measures of disease activity in RA. The scores were calculated by numerical summation of the number of tender and swollen joints (using the 28-joint count), and the patient's and physician's global assessment of disease activity.

Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)

Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)

FACIT fatigue scale is a 13- item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function, ranging from 0 (worst) to 52 (best). A score of less than 30 indicates severe fatigue.

DAS28-CRP and DAS28-ESR:

1. best is 0,
2. < 2.6 - remission,
3. ≥ 2.6 to ≤ 3.2 - low disease activity
4. > 3.2 to ≤ 5.1 - moderate disease activity
5. > 5.1 - high disease activity

Proportion of patients achieving EULAR good response (defined as DAS28 ≤ 3.2 and DAS28 improvement from Baseline > 1.2) and moderate response (defined as DAS28 ≤ 3.2 and DAS28 improvement > 0.6 and ≤ 1.2, or DAS28 > 3.2 and ≤ 5.1 and DAS28 improvement > 0.6 or DAS28 > 5.1 but DAS28 improvement > 1.2) at Weeks 36 and 48;

percentage of participants in DAS28-ESR categories up to week 48

Proportion of patients achieving EULAR/ACR Boolean remission criteria (defined as number of tender joints/swollen joints ≤ 1 and CRP (mg/dL) ≤ 1 and patient global assessment (1-10) ≤ 1) at Weeks 36 and 48;

ACR-N: negative is worsening, positive (up to 100) is an improvement

Proportion of patients in each disease activity category as defined by the Simplified Disease Activity Index (SDAI): high disease activity, SDAI > 26, moderate disease activity, SDAI > 11 to ≤ 26, low disease activity, SDAI > 3.3 to ≤ 11, and remission, SDAI ≤ 3.3 at Weeks 36 and 48.

Proportion of patients in each disease activity category as defined by the Clinical Disease Activity Index (CDAI): high disease activity, CDAI > 22, moderate disease activity, CDAI > 10 to ≤ 22, low disease activity, CDAI > 2.8 to ≤ 10, and remission, CDAI ≤ 2.8 at Weeks 36 and 48;

HAQ: from 0 (best) to 3 (worst)

FACIT: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue

Frequency of participants with injection site reactions in GP2015 and Enbrel

To assess the immunogenicity of continuous GP2015 treatment versus a treatment transition from Enbrel to GP2015 after 24 weeks of treatment by measuring the rate of ADA positive participants at Weeks 24, 30, 36 and 48. summary of ADA positive data up to week 48 using a 1% false positive cut point