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

Phase 3

Completed

Conditions: Rheumatoid Arthritis

Interventions: Biological: Adalimumab - US licensed Humira
Biological: Adalimumab - GP2017

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 353

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
US Licensed Humira	Adalimumab - US licensed Humira	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).
GP2017	Adalimumab - GP2017	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).

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): 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
Low Country Rheumatology, PA
🇺🇸
North Charleston, South Carolina, United States
Atlanta Center for Medical Research
🇺🇸
Atlanta, Georgia, United States
Marietta Rheumatology Associates, PC
🇺🇸
Marietta, Georgia, United States
Physician Research Collaboration
🇺🇸
Lincoln, Nebraska, United States
Medication Management, LLC
🇺🇸
Greensboro, North Carolina, United States
Sentara Medical Group Clinical Research
🇺🇸
Norfolk, Virginia, United States
Hospital Raja Perempuan Zainab II
🇲🇾
Kota Bahru, Kelantan, Malaysia
A.O.U. Senese Policlinico Santa Maria alle Scotte UOC Reumatologia
🇮🇹
Siena, Italy
McIlwain Medical Group, PA
🇺🇸
Tampa, Florida, United States
Hospital Pulau Pinang
🇲🇾
George Town, Pulau Pinang, Malaysia
Hospital Selayang
🇲🇾
Batu Caves, Selangor, Malaysia
Hospital Raja Permaisuri Bainun
🇲🇾
Ipoh, Perak, Malaysia
BayCare Medical Group, Inc
🇺🇸
Tampa, Florida, United States
Arizona Arthritis & Rheumatology
🇺🇸
Mesa, Arizona, United States
Ramesh C Gupta, MD
🇺🇸
Memphis, Tennessee, United States
Lovelace Scientific Resources, Inc.
🇺🇸
Venice, Florida, United States
Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz
🇭🇺
Bekescsaba, Hungary
Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
🇭🇺
Szeged, Hungary
Sun Valley Arthritis Center Ltd.
🇺🇸
Peoria, Arizona, United States
Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
🇲🇽
Durango, Mexico
Special Hospital for Rheumatic Diseases
🇷🇸
Novi Sad, Serbia
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
QPS MRA (Miami Research Associates)
🇺🇸
Miami, Florida, United States
West Broward Rheumatology Associates, Inc.
🇺🇸
Tamarac, Florida, United States
Medvin Clinical Research
🇺🇸
Covina, California, United States
MD Med Corp
🇺🇸
Hemet, California, United States
Talbert Medical Group
🇺🇸
Huntington Beach, California, United States
Family Clinical Trials, LLC.
🇺🇸
Pembroke Pines, Florida, United States
Omega Research Consultants Orlando
🇺🇸
Orlando, Florida, United States
Center for Arthritis & Osteoporosis
🇺🇸
Elizabethtown, Kentucky, United States
Montefiore Medical Center PRIME
🇺🇸
Lake Success, New York, United States
PMG Research of Wilmington, LLC
🇺🇸
Wilmington, North Carolina, United States
Austin Regional Clinic, P.A.
🇺🇸
Austin, Texas, United States
Tekton Research, Inc.
🇺🇸
Austin, Texas, United States
Revmatologicky Ustav
🇨🇿
Praha 2, Czechia
Revmatologicka a interni ambulance
🇨🇿
Kladno, Czechia
IMEDICA s.r.o.
🇨🇿
Brno, Czechia
MEDICAL PLUS s.r.o.
🇨🇿
Uherske Hradiste, Czechia
Revmacentrum MUDr. Mostera s.r.o.
🇨🇿
Zidenice, Czechia
Praxis Dr. Walter
🇩🇪
Rendsburg, Schleswig Holstein, Germany
Rheumatologische Schwerpunktpraxis Steglitz
🇩🇪
Berlin, Germany
HRF Hamburger Rheuma Forschungszentrum
🇩🇪
Hamburg, Germany
Sopron Medical Egeszsegugyi Szolgaltato Kft.
🇭🇺
Budapest, Hungary
Hevizgyogyfurdo es Szent Andras Reumakorhaz Reumatologia III
🇭🇺
Heviz, Hungary
Vital Medical Center
🇭🇺
Veszprem, Hungary
Centro Investigacion en Artritis y Osteoporosis S.C.
🇲🇽
Mexicali, Baja California Norte, Mexico
Investigacion y Biomedicina de Chihuahua, S.C.
🇲🇽
Chihuahua, Mexico
Hospital Sibu
🇲🇾
Sibu, Sarawak, Malaysia
Clinical Research Institute S.C.
🇲🇽
Tlalnepantla, Estado De Mexico, Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
🇲🇽
San Luis Potosi, San Luis Potos, Mexico
Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
🇵🇱
Lodz, Poland
Szpital Uniwersytecki nr 2 im.dr J. Biziela Dept of Clinical Reumatology
🇵🇱
Bydgoszcz, Poland
RCMed
🇵🇱
Sochaczew, Poland
RM Pharma Specialists SA de CV
🇲🇽
Mexico, Mexico
Centrum Kliniczno - Badawcze J. Brzezicki, B. Górnikiewicz-Brzezicka Lekarze Spółka Partnerska
🇵🇱
Elblag, Poland
Centrum Medyczne Pratia Gdynia ProFamilia Spolka Akcyjna, Oddzial w Gdyni
🇵🇱
Gdynia, Poland
Slaskie Centrum Reumatologii,Rehabilitacji i Zapobiegania Niepelnosprawnosci im. Gen. Jerzego Zietka
🇵🇱
Ustron, Poland
Niepubliczny Zakład Opieki Zdrowotnej "Biogenes" Sp. z o.o.
🇵🇱
Wroclaw, Poland
Ai Centrum Medyczne Sp. Z O.O. Sp.K.
🇵🇱
Poznan, Poland
Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati Sectia Reumatologie
🇷🇴
Galati, Romania
Spitalul Clinic Judetean de Urgenta Brasov Sectia Reumatologie
🇷🇴
Brasov, Romania
Spitalul Municipal Ploiesti Sectia Reumatologie
🇷🇴
Ploiesti, Romania
RK Medcenter SRL
🇷🇴
Iasi, Romania
SBIH of Nizhniy Novgorod region " City Clinical Hospital # 5"
🇷🇺
Nizhny Novgorod, Russian Federation
Spitalul Clinic Judetean de Urgenta Cluj Napoca Sectia Reumatologie
🇷🇴
Cluj-napoca, Romania
SPb SBIH "Clinical Rheumatological Hospital # 25"
🇷🇺
Saint Petersburg, Russian Federation
Research Institute of Emergency Medical Care
🇷🇺
Saint Petersburg, Russian Federation
SHI Ulyanovsk Reg Clinical Hospital
🇷🇺
Ul'yanovsk, Russian Federation
SBHI of Yaroslavl Region "Clinical Hospital #3"
🇷🇺
Yaroslavl, Russian Federation
Institute of Rheumatology
🇷🇸
Belgrade, Serbia
Hospital de Cruces
🇪🇸
Baracaldo, Spain
Hospital Universitario de Fuenlabrada
🇪🇸
Fuenlabrada, Spain
Corporacio Sanitaria Parc Tauli
🇪🇸
Sabadell, Spain
Hospital Infanta Luisa
🇪🇸
Sevilla, Spain
Royal Free Hospital
🇬🇧
London, United Kingdom
Princess Alexandra Hospital; Dept of Rheumatology; Williams Day Unit
🇬🇧
Harlow, Essex, United Kingdom
Albuquerque Clinical Trials, Inc.
🇺🇸
Albuquerque, New Mexico, United States
Arthritis and Rheumatology Consultants
🇺🇸
Edina, Minnesota, United States
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz Reumatologiai Osztaly
🇭🇺
Nyiregyhaza, Hungary
Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
🇮🇹
Milano, Italy