Clinical trial NCT02744755: Clinical Trial to Compare Treatment With GP2017 and Humira® in Patients With Rheumatoid Arthritis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
Collaborators: name: Hexal AG
First posted: 2016-04-20
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira
timeFrame: Study period 1: week 12
Secondary outcomes:
measure: Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira
timeFrame: Study period 1: week 24
measure: Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission
timeFrame: week 4, week 12 and week 24
measure: Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good Response
timeFrame: week 4, week 12 and week 24
measure: Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response
timeFrame: week 4, week 12 and week 24
measure: Study Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
timeFrame: week 4, week 12, week 24
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
timeFrame: study period 1: week 2, 4, 24
measure: Study Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24
timeFrame: Week 4, week 12 and week 24
measure: Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24;
timeFrame: Weeks 4, 12 and 24;
measure: Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;
timeFrame: Weeks 4, 12 and 24;
measure: Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24
timeFrame: Weeks 4, 12 and 24;
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)
timeFrame: Weeks 4, 12 and 24;
measure: Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
timeFrame: Week 4, week 12, week 24
measure: Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24
timeFrame: Week 4, week 12, week 24
measure: Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira
timeFrame: Treatment Period 1, 24 weeks
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)
timeFrame: baseline, week 2, week 4, week 12, week 24
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)
timeFrame: week 24, week 36, week 48
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
timeFrame: week 48
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
timeFrame: Weeks 48
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
timeFrame: week 48
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
timeFrame: week 48
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
timeFrame: week 48
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
timeFrame: up to 48 weeks
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology
state: Arizona
city: Peoria
country: United States
facility: Sun Valley Arthritis Center Ltd.
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: Hemet
country: United States
facility: MD Med Corp
state: California
city: Huntington Beach
country: United States
facility: Talbert Medical Group
state: California
city: Denver
country: United States
facility: Denver Arthritis Clinic
state: Colorado
city: Bridgeport
country: United States
facility: Joao Nascimento (Private Practice)
state: Connecticut
city: Aventura
country: United States
facility: Arthritis & Rheumatic Disease Specialties
state: Florida
city: Boca Raton
country: United States
facility: RASF - Clinical Research Center
state: Florida
city: Miami
country: United States
facility: QPS MRA (Miami Research Associates)
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Family Clinical Trials, LLC.
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates, Inc.
state: Florida
city: Tampa
country: United States
facility: McIlwain Medical Group, PA
state: Florida
city: Tampa
country: United States
facility: BayCare Medical Group, Inc
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Marietta
country: United States
facility: Marietta Rheumatology Associates, PC
state: Georgia
city: Elizabethtown
country: United States
facility: Center for Arthritis & Osteoporosis
state: Kentucky
city: Edina
country: United States
facility: Arthritis and Rheumatology Consultants
state: Minnesota
city: Lincoln
country: United States
facility: Physician Research Collaboration
state: Nebraska
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials, Inc.
state: New Mexico
city: Lake Success
country: United States
facility: Montefiore Medical Center PRIME
state: New York
city: Greensboro
country: United States
facility: Medication Management, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington, LLC
state: North Carolina
city: North Charleston
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Memphis
country: United States
facility: Ramesh C Gupta, MD
state: Tennessee
city: Austin
country: United States
facility: Austin Regional Clinic, P.A.
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc.
state: Texas
city: Norfolk
country: United States
facility: Sentara Medical Group Clinical Research
state: Virginia
city: Brno
country: Czechia
facility: IMEDICA s.r.o.
city: Kladno
country: Czechia
facility: Revmatologicka a interni ambulance
city: Praha 2
country: Czechia
facility: Revmatologicky Ustav
city: Uherske Hradiste
country: Czechia
facility: MEDICAL PLUS s.r.o.
city: Zidenice
country: Czechia
facility: Revmacentrum MUDr. Mostera s.r.o.
city: Rendsburg
country: Germany
facility: Praxis Dr. Walter
state: Schleswig Holstein
city: Berlin
country: Germany
facility: Rheumatologische Schwerpunktpraxis Steglitz
city: Hamburg
country: Germany
facility: HRF Hamburger Rheuma Forschungszentrum
city: Bekescsaba
country: Hungary
facility: Bekes Megyei Kozponti Korhaz Dr. Rethy Pal Tagkorhaz
city: Budapest
country: Hungary
facility: Sopron Medical Egeszsegugyi Szolgaltato Kft.
city: Heviz
country: Hungary
facility: Hevizgyogyfurdo es Szent Andras Reumakorhaz Reumatologia III
city: Nyiregyhaza
country: Hungary
facility: SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz Reumatologiai Osztaly
city: Szeged
country: Hungary
facility: Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont
city: Veszprem
country: Hungary
facility: Vital Medical Center
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Fatebenefratelli (Presidio Ospedale Sacco)
city: Siena
country: Italy
facility: A.O.U. Senese Policlinico Santa Maria alle Scotte UOC Reumatologia
city: Kota Bahru
country: Malaysia
facility: Hospital Raja Perempuan Zainab II
state: Kelantan
city: Ipoh
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
state: Perak
city: George Town
country: Malaysia
facility: Hospital Pulau Pinang
state: Pulau Pinang
city: Sibu
country: Malaysia
facility: Hospital Sibu
state: Sarawak
city: Batu Caves
country: Malaysia
facility: Hospital Selayang
state: Selangor
city: Mexicali
country: Mexico
facility: Centro Investigacion en Artritis y Osteoporosis S.C.
state: Baja California Norte
city: Tlalnepantla
country: Mexico
facility: Clinical Research Institute S.C.
state: Estado De Mexico
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
state: San Luis Potos
city: Chihuahua
country: Mexico
facility: Investigacion y Biomedicina de Chihuahua, S.C.
city: Durango
country: Mexico
facility: Instituto de Investigaciones Aplicadas a la Neurociencia A.C.
city: Mexico
country: Mexico
facility: RM Pharma Specialists SA de CV
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im.dr J. Biziela Dept of Clinical Reumatology
city: Elblag
country: Poland
facility: Centrum Kliniczno - Badawcze J. Brzezicki, B. Górnikiewicz-Brzezicka Lekarze Spółka Partnerska
city: Gdynia
country: Poland
facility: Centrum Medyczne Pratia Gdynia ProFamilia Spolka Akcyjna, Oddzial w Gdyni
city: Lodz
country: Poland
facility: Centrum Terapii Wspolczesnej J.M. Jasnorzewska sp. komandytowo-akcyjna
city: Poznan
country: Poland
facility: Ai Centrum Medyczne Sp. Z O.O. Sp.K.
city: Sochaczew
country: Poland
facility: RCMed
city: Ustron
country: Poland
facility: Slaskie Centrum Reumatologii,Rehabilitacji i Zapobiegania Niepelnosprawnosci im. Gen. Jerzego Zietka
city: Wroclaw
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej "Biogenes" Sp. z o.o.
city: Brasov
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Brasov Sectia Reumatologie
city: Cluj-napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj Napoca Sectia Reumatologie
city: Galati
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei" Galati Sectia Reumatologie
city: Iasi
country: Romania
facility: RK Medcenter SRL
city: Ploiesti
country: Romania
facility: Spitalul Municipal Ploiesti Sectia Reumatologie
city: Nizhny Novgorod
country: Russian Federation
facility: SBIH of Nizhniy Novgorod region " City Clinical Hospital # 5"
city: Saint Petersburg
country: Russian Federation
facility: SPb SBIH "Clinical Rheumatological Hospital # 25"
city: Saint Petersburg
country: Russian Federation
facility: Research Institute of Emergency Medical Care
city: Ul'yanovsk
country: Russian Federation
facility: SHI Ulyanovsk Reg Clinical Hospital
city: Yaroslavl
country: Russian Federation
facility: SBHI of Yaroslavl Region "Clinical Hospital #3"
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Novi Sad
country: Serbia
facility: Special Hospital for Rheumatic Diseases
city: Baracaldo
country: Spain
facility: Hospital de Cruces
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital; Dept of Rheumatology; Williams Day Unit
state: Essex
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
References:
citation: Blauvelt A, Leonardi CL, Gaylis N, Jauch-Lembach J, Balfour A, Lemke L, Hachaichi S, Brueckmann I, Festini T, Wiland P. Treatment with SDZ-ADL, an Adalimumab Biosimilar, in Patients with Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis: Results of Patient-Reported Outcome Measures from Two Phase III Studies (ADMYRA and ADACCESS). BioDrugs. 2021 Mar;35(2):229-238. doi: 10.1007/s40259-021-00470-1. Epub 2021 Mar 2.
citation: Huizinga TWJ, Torii Y, Muniz R. Adalimumab Biosimilars in the Treatment of Rheumatoid Arthritis: A Systematic Review of the Evidence for Biosimilarity. Rheumatol Ther. 2021 Mar;8(1):41-61. doi: 10.1007/s40744-020-00259-8. Epub 2020 Dec 1.
citation: Wiland P, Jeka S, Dokoupilova E, Brandt-Jurgens J, Miranda Limon JM, Cantalejo Moreira M, Cabello RV, Jauch-Lembach J, Thakur A, Haliduola H, Brueckmann I, Gaylis NB. Switching to Biosimilar SDZ-ADL in Patients with Moderate-to-Severe Active Rheumatoid Arthritis: 48-Week Efficacy, Safety and Immunogenicity Results From the Phase III, Randomized, Double-Blind ADMYRA Study. BioDrugs. 2020 Dec;34(6):809-823. doi: 10.1007/s40259-020-00447-6.