Rheumatoid Arthritis
Conditions
Brief summary
Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis
Detailed description
The purpose of this study is to demonstrate similar efficacy and safety of GP2017 and US-licensed Humira® in patients with moderate to severe rheumatoid arthritis (RA) with inadequate response to Disease modifying anti-rheumatic drugs (DMARDs), including methotrexate (MTX).
Interventions
BIOLOGICALAdalimumab - GP2017
Adalimumab - GP2017
BIOLOGICALAdalimumab - US licensed Humira
Adalimumab - US licensed Humira
Sponsors
Hexal AG
Sandoz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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. Patients must have been diagnosed with RA ≥ 6 months prior to screening 2. Patients must have active disease, defined as DAS28-CRP ≥ 3.2 at the time of screening 3. Patients must have CRP levels above 5mg/l or ESR levels above the upper limits of normal 4. Patients must have had inadequate clinical response to MTX 10 - 25 mg/week
Exclusion criteria
1. Previous treatment with adalimumab, other anti-TNFα therapies or cell depleting agents, e.g. anti-CD20 therapy 2. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during treatment 3. Nursing (lactating) or pregnant women 4. History of or ongoing inflammatory or autoimmune diseases other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc. 5. Systemic corticosteroids \> 7.5mg/day within 4 weeks prior to baseline 6. History or presence of cancer or lymphoproliferative disease other than a successfully and completely treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix and/or removed non-invasive colon polyps, with no evidence of recurrence 7. History of uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (New York Heart Association III-IV), active peptic ulcer disease, recent stroke (within 3 months) 8. Subject known to have immune deficiency, history of positive human immunodeficiency virus (HIV) status or immunocompromised for other reasons 9. History of clinically significant hematologic (e.g. severe anemia, leucopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis) 10. History of persistent chronic infection; recurrent infection or active infections 11. History of tuberculosis, presence of active tuberculosis, latent tuberculosis as detected by imaging (e.g. chest X-ray, chest Computerized Tomography(CT) scan, Magnetic Resonance Imaging (MRI)) and/ or positive QuantiFERON-TB Gold test (QFT) 12. History or evidence of opportunistic infections, e.g. histoplasmosis, listeriosis, legionellosis 13. Positive serology Hepatitis B (either HBsAg or anti-HBc) or Hepatitis C (positive HCV-Ab or HCV-RNA) indicative of previous or current infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira | Study period 1: week 12 | Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value \>5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value \< 2.6 corresponds to remission DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GDA or GH + 0.96 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) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | week 4, week 12 and week 24 | Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP \< 2.6 ) |
| Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | week 4, week 12 and week 24 | Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28\<=3.2 at post-baseline assessment timepoint(s) with an improvement of \>1.2 in DAS28 from baseline.) |
| Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | week 4, week 12 and week 24 | Proportion of patients achieving European League against Rheumatism (EULAR) moderate response (defined as DAS28\<=3.2 at post-baseline assessment timepoint(s) with an improvement of \>0.6 to \<=1.2 from baseline or DAS28 \>3.2 to \<=5.1 with an improvement of \>0.6 to \<=1.2 or of \>1.2 from baseline or DAS28 \>5.1 with an improvement of \>1.2 from baseline) ; |
| Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 4, week 12, week 24 | Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joint count 28 \<=1 and swollen joint count 28 \<=1, CRP level (mg/dL) \<=1 and patient's global assessment \<=1 on a scale of 1-10 (corresponding to \<=10 on a scale of 1-100). |
| Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | study period 1: week 2, 4, 24 | 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.Values range from 0 to 10. Higher values mean a higher disease activity. |
| Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | Week 4, week 12 and week 24 | ACR20 response was defined if a patient fulfilled all 3 criteria below: -at least 20% improvement in tender 68 joint count -at least 20% improvement in swollen 66 joint-count; And at least 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 index(HAQ-DI© 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. |
| Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Weeks 4, 12 and 24; | Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst).The HAQ© was scored in accordance with the recommendation from the developers outlined in the HAQ PACK from Stanford University, California. Ramey Dr, Fries JF, Singh G. in B. Spilker Quality of Life and Pharmacoleconomics in Clinical Trials, 2nd ed, The Health Assessment Questionnaire 1995 -- Status and Review. Philadelphia: Lippincott-Raven Pub., 1996, p 227 - 237. Fries JF, Spitz P, Kraines G, Holman H. Measurement of Patient Outcome in Arthritis, Arthritis and Rheumatism, 1980, 23:137-145. |
| Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Weeks 4, 12 and 24; | Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst) |
| Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Weeks 4, 12 and 24; | Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst) |
| Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Weeks 4, 12 and 24; | 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). |
| Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira | Study period 1: week 24 | Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value \>5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value \< 2.6 corresponds to remission DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GDA or GH + 0.96 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) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm |
| Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | Week 4, week 12, week 24 | Outcome measure 13 presents changes in ESR measures in blood while outcome measure 7 presents changes in DAS28-ESR scores (calculated composite score to measure the disease activity) |
| Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Treatment Period 1, 24 weeks | Incidence of injection site reactions in GP2017 and Humira |
| Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | baseline, week 2, week 4, week 12, week 24 | Frequency of patients having anti-drug antibody (ADA) during 24 weeks |
| Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | week 24, week 36, week 48 | Frequency of patients having anti-drug antibody (ADA) during 24 weeks |
| Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | week 48 | — |
| Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Weeks 48 | Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst) |
| Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48 | week 48 | — |
| Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | week 48 | FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue |
| Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | week 48 | 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.Values range from 0 to 10. Higher values mean a higher disease activity. |
| Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | up to 48 weeks | Incidence of injection site reactions |
| Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | Week 4, week 12, week 24 | Outcome measure 13 presents changes in CRP measures in blood while Outome measure 7 presents changes in DAS28-CRP scores (calculated composite score to measure the disease activity) |
Countries
Czechia, Germany, Hungary, Italy, Malaysia, Mexico, Poland, Romania, Russia, Serbia, Spain, United Kingdom, United States
Participant flow
Recruitment details
353 patients were randomized (1:1)and received at least one dose of study drug; 303 patients completed the study.Eligible patients in the Humira group who completed Study Period 1 (baseline to week 24) with an at least moderate response by DAS28-CRP score were switched to GP2017 treatment during Study Period 2 (Week 24 to week 48).
Pre-assignment details
Full analysis set: randomized patients (study drug assigned) Per protocol set study period 1 (SP1) / study period 2(SP2): patients who completed Week 12 (SP1) / Week 48 (SP2) without major protocol deviations and received at least 5 doses of study drug up to Week 10 (SP1) / 10 doses of IMP from Week 24 to Week 46 (SP2)
Participants by arm
| Arm | Count |
|---|---|
| GP2017 Group 1 received treatment with 40 mg GP2017 in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response continued treatment with 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2). | 177 |
| Humira / Switched GP2017 Group 2 received treatment with 40 mg Humira in 0.8 mL of solution administered subcutaneously from pre-filled syringes up to 24 weeks (study Period 1) after which patients achieving at least a moderate clinical response were switched to 40mg GP2017 subcutaneous injection up to 46 weeks (study Period 2). | 176 |
| Total | 353 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Study Period 1 | Adverse Event | 1 | 1 |
| Study Period 1 | Lack of Efficacy | 1 | 0 |
| Study Period 1 | Lost to Follow-up | 1 | 1 |
| Study Period 1 | not defined | 0 | 1 |
| Study Period 1 | Pregnancy | 1 | 0 |
| Study Period 1 | Protocol Violation | 2 | 1 |
| Study Period 1 | Withdrawal by Subject | 8 | 4 |
| Study Period 2 | Adverse Event | 5 | 0 |
| Study Period 2 | Lack of Efficacy | 3 | 2 |
| Study Period 2 | Lost to Follow-up | 0 | 2 |
| Study Period 2 | not defined | 3 | 2 |
| Study Period 2 | Protocol Violation | 1 | 0 |
| Study Period 2 | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | GP2017 | Humira / Switched GP2017 | Total |
|---|---|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 12.81 | 53.8 years STANDARD_DEVIATION 12.22 | 53.3 years STANDARD_DEVIATION 12.51 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 14 Participants | 15 Participants | 29 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 152 Participants | 152 Participants | 304 Participants |
| Sex: Female, Male Female | 153 Participants | 142 Participants | 295 Participants |
| Sex: Female, Male Male | 24 Participants | 34 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 177 | 0 / 176 | 0 / 159 | 0 / 166 | 0 / 177 | 0 / 176 |
| other Total, other adverse events | 83 / 177 | 74 / 176 | 28 / 159 | 26 / 166 | 94 / 177 | 80 / 176 |
| serious Total, serious adverse events | 5 / 177 | 4 / 176 | 4 / 159 | 6 / 166 | 7 / 177 | 10 / 176 |
Outcome results
Primary
Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira
Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value \>5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value \< 2.6 corresponds to remission DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GDA or GH + 0.96 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) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm
Time frame: Study period 1: week 12
Population: Treatment Period 1 Per-Protocol set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2017 | Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira | -2.16 scores on a scale | Standard Error 0.114 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira | -2.18 scores on a scale | Standard Error 0.11 |
Comparison: Therapeutic equivalence in terms of change from baseline in DAS28-CRP at week 12 will be concluded if the 95% confidence interval for the LS mean difference between GP2017 and Humira is contained within the interval \[-0.6; 0.6\]. A mixed-model repeated measures analysis was performed for DAS28-CRP change from baseline including treatment, stratification factors, time, the interaction between time (visits) and treatment all as categorical variables, and baseline DAS28-CRP as a continuous variable.95% CI: [-0.24, 0.27]
Comparison: Therapeutic equivalence in terms of change from baseline in DAS28-CRP at week 12 will be concluded if the 90% confidence interval for the LS mean difference between GP2017 and Humira is contained within the interval \[-0.6; 0.6\]. A mixed-model repeated measures analysis was performed for DAS28-CRP change from baseline including treatment, stratification factors, time, the interaction between time (visits) and treatment all as categorical variables, and baseline DAS28-CRP as a continuous variable.90% CI: [-0.19, 0.23]
Secondary
Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira
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.Values range from 0 to 10. Higher values mean a higher disease activity.
Time frame: study period 1: week 2, 4, 24
Population: Treatment Period 1 Per-Protocol set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 2 | -0.86 scores on a scale | Standard Error 0.107 |
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 4 | -1.31 scores on a scale | Standard Error 0.112 |
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 24 | -2.61 scores on a scale | Standard Error 0.109 |
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 2 | -0.94 scores on a scale | Standard Error 0.115 |
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 4 | -1.51 scores on a scale | Standard Error 0.124 |
| GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 24 | -2.97 scores on a scale | Standard Error 0.127 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 4 | -1.51 scores on a scale | Standard Error 0.117 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 2 | -0.92 scores on a scale | Standard Error 0.101 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 2 | -0.98 scores on a scale | Standard Error 0.109 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 4 | -1.36 scores on a scale | Standard Error 0.105 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 ESR week 24 | -3.16 scores on a scale | Standard Error 0.12 |
| Humira / Switched GP2017 | Study Period 1: Change in DAS28-CRP and DAS28-ESR Scores From Baseline to Week 24 in Patients Treated With GP2017 and Patients Treated With Humira | DAS28 CRP week 24 | -2.83 scores on a scale | Standard Error 0.103 |
Secondary
Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;
Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst).The HAQ© was scored in accordance with the recommendation from the developers outlined in the HAQ PACK from Stanford University, California. Ramey Dr, Fries JF, Singh G. in B. Spilker Quality of Life and Pharmacoleconomics in Clinical Trials, 2nd ed, The Health Assessment Questionnaire 1995 -- Status and Review. Philadelphia: Lippincott-Raven Pub., 1996, p 227 - 237. Fries JF, Spitz P, Kraines G, Holman H. Measurement of Patient Outcome in Arthritis, Arthritis and Rheumatism, 1980, 23:137-145.
Time frame: Weeks 4, 12 and 24;
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 4 | -0.32 score on a scale | Standard Deviation 0.519 |
| GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 12 | -0.50 score on a scale | Standard Deviation 0.576 |
| GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 24 | -0.63 score on a scale | Standard Deviation 0.61 |
| Humira / Switched GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 4 | -0.32 score on a scale | Standard Deviation 0.449 |
| Humira / Switched GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 12 | -0.47 score on a scale | Standard Deviation 0.501 |
| Humira / Switched GP2017 | Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; | Week 24 | -0.59 score on a scale | Standard Deviation 0.543 |
Secondary
Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Outcome measure 13 presents changes in CRP measures in blood while Outome measure 7 presents changes in DAS28-CRP scores (calculated composite score to measure the disease activity)
Time frame: Week 4, week 12, week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 4 | -4.79 mg/L | Standard Deviation 8.728 |
| GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 12 | -5.98 mg/L | Standard Deviation 11.27 |
| GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 24 | -2.51 mg/L | Standard Deviation 19.176 |
| Humira / Switched GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 4 | -4.93 mg/L | Standard Deviation 12.128 |
| Humira / Switched GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 12 | -5.07 mg/L | Standard Deviation 11.791 |
| Humira / Switched GP2017 | Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | CRP change from baseline week 24 | -5.30 mg/L | Standard Deviation 13.726 |
Secondary
Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Outcome measure 13 presents changes in ESR measures in blood while outcome measure 7 presents changes in DAS28-ESR scores (calculated composite score to measure the disease activity)
Time frame: Week 4, week 12, week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 4 | -16.17 mm/h | Standard Deviation 14.693 |
| GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 12 | -17.33 mm/h | Standard Deviation 16.214 |
| GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 24 | -19.60 mm/h | Standard Deviation 20.494 |
| Humira / Switched GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 4 | -13.98 mm/h | Standard Deviation 15.823 |
| Humira / Switched GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 12 | -15.08 mm/h | Standard Deviation 31.15 |
| Humira / Switched GP2017 | Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 | ESR change from baseline week 24 | -20.49 mm/h | Standard Deviation 18.255 |
Secondary
Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline)
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).
Time frame: Weeks 4, 12 and 24;
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 4 | 6.59 score on a scale | Standard Deviation 7.949 |
| GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 12 | 10.49 score on a scale | Standard Deviation 9.218 |
| GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 24 | 12.57 score on a scale | Standard Deviation 10.76 |
| Humira / Switched GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 4 | 7.25 score on a scale | Standard Deviation 8.591 |
| Humira / Switched GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 12 | 10.62 score on a scale | Standard Deviation 9.134 |
| Humira / Switched GP2017 | Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) | Week 24 | 12.72 score on a scale | Standard Deviation 9.451 |
Secondary
Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients)
Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Time frame: baseline, week 2, week 4, week 12, week 24
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 2 | 12 Participants |
| GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 12 | 16 Participants |
| GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 4 | 14 Participants |
| GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 24 | 23 Participants |
| GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Baseline | 10 Participants |
| Humira / Switched GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 24 | 25 Participants |
| Humira / Switched GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Baseline | 6 Participants |
| Humira / Switched GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 2 | 10 Participants |
| Humira / Switched GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 4 | 22 Participants |
| Humira / Switched GP2017 | Study Period 1 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 or Humira (Positive Patients) | Week 12 | 23 Participants |
Secondary
Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira
Incidence of injection site reactions in GP2017 and Humira
Time frame: Treatment Period 1, 24 weeks
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | incidence of injection site reactions | 7 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions MILD | 7 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions MODERATE | 0 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions SEVERE | 0 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site erythema | 2 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site pruritus | 2 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site pain | 2 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site inflammation | 2 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site rash | 0 Participants |
| GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site discolouration | 0 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site inflammation | 0 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | incidence of injection site reactions | 11 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site pruritus | 3 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions MILD | 7 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site discolouration | 1 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions MODERATE | 4 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site pain | 1 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | injection site reactions SEVERE | 0 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site rash | 2 Participants |
| Humira / Switched GP2017 | Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Injection site erythema | 6 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24
ACR20 response was defined if a patient fulfilled all 3 criteria below: -at least 20% improvement in tender 68 joint count -at least 20% improvement in swollen 66 joint-count; And at least 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 index(HAQ-DI© 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.
Time frame: Week 4, week 12 and week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 12 | 100 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 24 | 78 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 4 | 25 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 4 | 7 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 24 | 111 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 12 | 24 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 12 | 53 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 24 | 48 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 4 | 64 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 24 | 53 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 4 | 71 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 12 | 106 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR20 response Week 24 | 130 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 4 | 25 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 12 | 67 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR50 response Week 24 | 98 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 4 | 9 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24 | ACR70 response Week 12 | 35 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joint count 28 \<=1 and swollen joint count 28 \<=1, CRP level (mg/dL) \<=1 and patient's global assessment \<=1 on a scale of 1-10 (corresponding to \<=10 on a scale of 1-100).
Time frame: week 4, week 12, week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 4 | 4 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 12 | 8 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 24 | 19 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 4 | 0 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 24 | 26 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria | week 12 | 12 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response
Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28\<=3.2 at post-baseline assessment timepoint(s) with an improvement of \>1.2 in DAS28 from baseline.)
Time frame: week 4, week 12 and week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 4 | 22 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 12 | 51 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 24 | 76 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 4 | 25 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 12 | 63 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response | Good response week 24 | 93 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response
Proportion of patients achieving European League against Rheumatism (EULAR) moderate response (defined as DAS28\<=3.2 at post-baseline assessment timepoint(s) with an improvement of \>0.6 to \<=1.2 from baseline or DAS28 \>3.2 to \<=5.1 with an improvement of \>0.6 to \<=1.2 or of \>1.2 from baseline or DAS28 \>5.1 with an improvement of \>1.2 from baseline) ;
Time frame: week 4, week 12 and week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 4 | 63 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 12 | 64 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 24 | 42 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 4 | 78 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 12 | 62 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response | Moderate response week 24 | 42 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission
Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP \< 2.6 )
Time frame: week 4, week 12 and week 24
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 4 | 15 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 12 | 32 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 24 | 49 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 4 | 7 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 12 | 38 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission | EULAR remission week 24 | 71 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;
Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)
Time frame: Weeks 4, 12 and 24;
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 4 | 27 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 12 | 38 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 24 | 46 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 4 | 33 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 12 | 40 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; | Week 24 | 50 Participants |
Secondary
Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24
Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)
Time frame: Weeks 4, 12 and 24;
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 4 | 106 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 12 | 102 Participants |
| GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 24 | 91 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 4 | 117 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 12 | 109 Participants |
| Humira / Switched GP2017 | Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 | Week 24 | 106 Participants |
Secondary
Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira
Disease activity score (DAS) 28-CRP is based on 28-joint count (tender and swollen joints), C-reactive protein and patient's assessment of global disease activity (GDA) or general health (GH), values range from 0.96 to 10.0 while higher values mean a higher disease activity. • A DAS28-CRP value \>5.1 corresponds to a high disease activity • A DAS28-CRP value between 3.2 and 5.1 corresponds to a moderate disease activity • A DAS28-CRP value between 2.6 and 3.2 corresponds to a low disease activity • A DAS28-CRP value \< 2.6 corresponds to remission DAS28-CRP = 0.56 \* sqrt(tender28) + 0.28\* sqrt(swollen28) + 0.36 \* ln(CRP+1) + 0.014 \* GDA or GH + 0.96 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) • GDA is the global disease activity measured on a Visual Analogue Scale (VAS) of 100 mm
Time frame: Study period 1: week 24
Population: Treatment Period 1 Per-Protocol set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GP2017 | Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira | -1.85 scores on a scale | Standard Error 0.098 |
| Humira / Switched GP2017 | Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira | -1.93 scores on a scale | Standard Error 0.092 |
Comparison: ANCOVA model included treatment, body weight as per CRF, prior therapy as per CRF, region as per CRF as fixed effects and baseline DAS28-CRP values as covariate.95% CI: [-0.11, 0.27]ANCOVA
Comparison: ANCOVA model included treatment, body weight as per CRF, prior therapy as per CRF, region as per CRF as fixed effects and baseline DAS28-CRP values as covariate.90% CI: [-0.08, 0.24]ANCOVA
Secondary
Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
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.Values range from 0 to 10. Higher values mean a higher disease activity.
Time frame: week 48
Population: Treatment period 2 per protocol set. Patients with data available
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GP2017 | Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | DAS28-CRP Week 48, change from week 24 | -0.10 score on a scale | Standard Deviation 0.893 |
| GP2017 | Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | DAS28-ESR Week 48, change from week 24 | -0.04 score on a scale | Standard Deviation 1.015 |
| Humira / Switched GP2017 | Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | DAS28-CRP Week 48, change from week 24 | 0.00 score on a scale | Standard Deviation 0.941 |
| Humira / Switched GP2017 | Study Period 2: Changes From Week 24 at Week 48 in DAS28-CRP and DAS28-ESR Scores in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | DAS28-ESR Week 48, change from week 24 | 0.00 score on a scale | Standard Deviation 1.025 |
Secondary
Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue
Time frame: week 48
Population: Treatment period 2 per protocol set. Patients with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2017 | Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | -0.65 score on a scale | Standard Deviation 7.421 |
| Humira / Switched GP2017 | Study Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | -0.85 score on a scale | Standard Deviation 7.476 |
Secondary
Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)
Time frame: Weeks 48
Population: Treatment period 1 per protocol set. Patients with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| GP2017 | Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | 0.01 score on a scale | Standard Deviation 0.358 |
| Humira / Switched GP2017 | Study Period 2 - Health Assessment Questionnaire-Disability Index (HAQ-DI©) Changes From Week 24 at Week 48 in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | -0.03 score on a scale | Standard Deviation 0.427 |
Secondary
Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients)
Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Time frame: week 24, week 36, week 48
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 24 | 22 Participants |
| GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 36 | 21 Participants |
| GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 48 | 12 Participants |
| Humira / Switched GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 24 | 25 Participants |
| Humira / Switched GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 36 | 22 Participants |
| Humira / Switched GP2017 | Study Period 2 - Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Formation Against Adalimumab in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira (Positive Patients) | Week 48 | 12 Participants |
Secondary
Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Incidence of injection site reactions
Time frame: up to 48 weeks
Population: Safety Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Number of patients with ISRs | 1 Participants |
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Injection site erythema | 1 Participants |
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Injection site pruritus | 0 Participants |
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions MILD | 1 Participants |
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions MODERATE | 0 Participants |
| GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions SEVERE | 0 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions MODERATE | 1 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Number of patients with ISRs | 2 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions MILD | 1 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Injection site erythema | 2 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | injection site reactions SEVERE | 0 Participants |
| Humira / Switched GP2017 | Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira | Injection site pruritus | 1 Participants |
Secondary
Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira
Time frame: week 48
Population: Treatment period 2 per protocol set. Patients with data available
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR20 response Week 48 | 93 Participants |
| GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR50 response Week 48 | 72 Participants |
| GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR70 response Week 48 | 49 Participants |
| Humira / Switched GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR20 response Week 48 | 111 Participants |
| Humira / Switched GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR50 response Week 48 | 81 Participants |
| Humira / Switched GP2017 | Study Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Week 48, in Patients Treated With GP2017 Who Continued GP2017 or Switched to GP2017 From Humira | ACR70 response Week 48 | 55 Participants |
Secondary
Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48
Time frame: week 48
Population: Treatment period 2 per protocol set. Patients with data available
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GP2017 | Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48 | 45 Participants |
| Humira / Switched GP2017 | Study Period 2 :Proportion of Patients Treated Continuously With GP2017 and Patients Treated With GP2017 After Switch From Humira Achieving HAQ-DI© Score in Normal Range ≤0.5 at Week 48 | 52 Participants |