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

Phase 3

Completed

• Conditions: Rheumatoid Arthritis

• Registration Number: NCT02744755
• Lead Sponsor: Sandoz

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).

Study Timeline

• Study Start: 2016-03-31
• Study First Submitted: 2016-04-12
• Study First Submitted QC: 2016-04-15
• Study First Posted: 2016-04-20
• Primary Completion: 2017-01-31
• Disposition First Submitted: 2017-02-14
• Disposition First Submitted QC: 2017-02-14
• Disposition First Posted: 2017-02-15
• Study Completion: 2017-09-26
• Results First Submitted: 2018-09-21
• Status Verified: 2018-11
• Results First Submitted QC: 2018-11-30
• Last Update Submitted: 2018-11-30
• Results First Posted: 2018-12-19
• Last Update Posted: 2018-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 353

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: 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- 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- 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 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: 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 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 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 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: 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 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 - 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 -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 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 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)
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: 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

Trial Locations

Locations (83)

Arizona Arthritis & Rheumatology; 🇺🇸 Mesa, Arizona, United States

Sun Valley Arthritis Center Ltd.; 🇺🇸 Peoria, Arizona, United States

Medvin Clinical Research; 🇺🇸 Covina, California, United States

MD Med Corp; 🇺🇸 Hemet, California, United States

Talbert Medical Group; 🇺🇸 Huntington Beach, California, United States

Denver Arthritis Clinic; 🇺🇸 Denver, Colorado, United States

Joao Nascimento (Private Practice); 🇺🇸 Bridgeport, Connecticut, United States

Arthritis & Rheumatic Disease Specialties; 🇺🇸 Aventura, Florida, United States

RASF - Clinical Research Center; 🇺🇸 Boca Raton, Florida, United States

QPS MRA (Miami Research Associates); 🇺🇸 Miami, Florida, United States

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