Brief Summary
Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis
Brief Title
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).
Completion Date
Completion Date Type
Actual
Conditions
Rheumatoid Arthritis
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02744755
Org Class
Industry
Org Full Name
Sandoz
Org Study Id
GP17-302
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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
Outcome Measure
Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira
Outcome Time Frame
Study period 1: week 12
Secondary Ids
Secondary Id
2015-003433-10
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
Study period 1: week 24
Outcome Measure
Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira
Outcome Description
Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP \< 2.6 )
Outcome Time Frame
week 4, week 12 and week 24
Outcome Measure
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission
Outcome Description
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.)
Outcome Time Frame
week 4, week 12 and week 24
Outcome Measure
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response
Outcome Description
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) ;
Outcome Time Frame
week 4, week 12 and week 24
Outcome Measure
Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response
Outcome Description
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).
Outcome Time Frame
week 4, week 12, week 24
Outcome Measure
Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
Outcome Description
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.
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.
Outcome Time Frame
study period 1: week 2, 4, 24
Outcome Measure
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
Outcome Description
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.
-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.
Outcome Time Frame
Week 4, week 12 and week 24
Outcome Measure
Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24
Outcome Description
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.
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.
Outcome Time Frame
Weeks 4, 12 and 24;
Outcome Measure
Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;
Outcome Description
Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)
Outcome Time Frame
Weeks 4, 12 and 24;
Outcome Measure
Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;
Outcome Description
Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)
Outcome Time Frame
Weeks 4, 12 and 24;
Outcome Measure
Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24
Outcome Description
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).
Outcome Time Frame
Weeks 4, 12 and 24;
Outcome Measure
Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline)
Outcome Description
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)
Outcome Time Frame
Week 4, week 12, week 24
Outcome Measure
Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Outcome Description
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)
Outcome Time Frame
Week 4, week 12, week 24
Outcome Measure
Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
Outcome Description
Incidence of injection site reactions in GP2017 and Humira
Outcome Time Frame
Treatment Period 1, 24 weeks
Outcome Measure
Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira
Outcome Description
Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Outcome Time Frame
baseline, week 2, week 4, week 12, week 24
Outcome Measure
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)
Outcome Description
Frequency of patients having anti-drug antibody (ADA) during 24 weeks
Outcome Time Frame
week 24, week 36, week 48
Outcome Measure
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)
Outcome Time Frame
week 48
Outcome Measure
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
Outcome Description
Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)
Outcome Time Frame
Weeks 48
Outcome Measure
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
Outcome Time Frame
week 48
Outcome Measure
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
Outcome Description
FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue
Outcome Time Frame
week 48
Outcome Measure
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
Outcome Description
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.
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.
Outcome Time Frame
week 48
Outcome Measure
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
Outcome Description
Incidence of injection site reactions
Outcome Time Frame
up to 48 weeks
Outcome Measure
Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Clement Tagoe
Investigator Email
ctagoe@montefiore.org
Investigator Phone