Clinical Trial to Compare Treatment With GP2017 and Humira® in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis

Detailed Description
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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).

Official Title
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A Randomized, Double-blind, Parallel-group, Multicenter Study to Demonstrate Similar Efficacy and to Compare Safety and Immunogenicity of GP2017 and Humira® in Patients With Moderate to Severe Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Adalimumab - GP2017
* Biological: Adalimumab - US licensed Humira


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have been diagnosed with RA ≥ 6 months prior to screening Patients must have active disease, defined as DAS28-CRP ≥ 3.2 at the time of screening Patients must have CRP levels above 5mg/l or ESR levels above the upper limits of normal Patients must have had inadequate clinical response to MTX 10 - 25 mg/week Exclusion Criteria: Previous treatment with adalimumab, other anti-TNFα therapies or cell depleting agents, e.g. anti-CD20 therapy 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 Nursing (lactating) or pregnant women History of or ongoing inflammatory or autoimmune diseases other than RA, e.g. mixed connective tissue disease, systemic lupus erythematosus etc. Systemic corticosteroids > 7.5mg/day within 4 weeks prior to baseline 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 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) Subject known to have immune deficiency, history of positive human immunodeficiency virus (HIV) status or immunocompromised for other reasons History of clinically significant hematologic (e.g. severe anemia, leucopenia, thrombocytopenia), renal or liver disease (e.g. glomerulonephritis, fibrosis, cirrhosis, hepatitis) History of persistent chronic infection; recurrent infection or active infections 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) History or evidence of opportunistic infections, e.g. histoplasmosis, listeriosis, legionellosis Positive serology Hepatitis B (either HBsAg or anti-HBc) or Hepatitis C (positive HCV-Ab or HCV-RNA) indicative of previous or current infections

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GP2017<br>Group 1 will receive treatment with 40mg GP2017 (Adalimumab - GP2017) by subcutaneous injection every other week up to 24 weeks (Study Period 1) at which patients achieving at least a moderate clinical response continue treatment with 40mg GP2017 subcutaneous injection every other week up to 48 weeks (Study Period 2). | Biological: Adalimumab - GP2017<br>* Adalimumab - GP2017<br>* Other names: GP2017;|
| Active Comparator: US Licensed Humira<br>Group 2 will receive treatment with 40mg Humira® (Adalimumab - US licensed Humira®) by subcutaneous injection every other week up to 24 weeks (Study Period 1) at which patients achieving at least a moderate clinical response will be switched to treatment with 40mg GP2017 subcutaneous injection every other week up to 48 weeks (Study Period 2). | Biological: Adalimumab - US licensed Humira<br>* Adalimumab - US licensed Humira<br>* Other names: Humira - Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Study period 1: week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Study period 1: week 24 | 
| 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 ) | week 4, week 12 and week 24 | 
| 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.) | week 4, week 12 and week 24 | 
| 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) ; | week 4, week 12 and week 24 | 
| 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). | week 4, week 12, week 24 | 
| 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: best is 0, < 2.6 - remission, ≥ 2.6 to ≤ 3.2 - low disease activity > 3.2 to ≤ 5.1 - moderate disease activity > 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: week 2, 4, 24 | 
| 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. | Week 4, week 12 and week 24 | 
| 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. | Weeks 4, 12 and 24; | 
| 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) | Weeks 4, 12 and 24; | 
| 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) | Weeks 4, 12 and 24; | 
| 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). | Weeks 4, 12 and 24; | 
| 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) | Week 4, week 12, week 24 | 
| 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) | Week 4, week 12, week 24 | 
| Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira | Incidence of injection site reactions in GP2017 and Humira | Treatment Period 1, 24 weeks | 
| 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 | baseline, week 2, week 4, week 12, week 24 | 
| 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 | week 24, week 36, week 48 | 
| 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 | Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst) | Weeks 48 | 
| 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 | FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue | week 48 | 
| 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: best is 0, < 2.6 - remission, ≥ 2.6 to ≤ 3.2 - low disease activity > 3.2 to ≤ 5.1 - moderate disease activity > 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. | week 48 | 
| 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 | up to 48 weeks |