Clinical trial NCT02638259: Comparative Efficacy and Safety Study of GP2015 and Enbrel® in Patients With Rheumatoid Arthritis
Official title: A Randomized, Double-blind, Parallel-group Phase III Study to Demonstrate Equivalent Efficacy and to Compare Safety & Immunogenicity of GP2015 and Enbrel® (EU Authorized) in Patients With Moderate to Severe, Active Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Biosimilars
Rheumatoid Arthritis
Etanercept
Lead sponsor: Sandoz
Sponsor class: INDUSTRY
First posted: 2015-12-23
Enrollment: 376
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: Demonstrate equivalent efficacy of GP2015 and EU-authorized Enbrel in patients with moderate to severe, active (RA) who had an inadequate response to disease modifying anti-rheumatic drugs (DMARD) including methotrexate (MTX).

Detailed description: Demonstrate equivalent efficacy of GP2015 and EU-authorized Enbrel in patients with moderate to severe, active (RA) who had an inadequate response to disease modifying anti-rheumatic drugs (DMARD) including methotrexate (MTX). In addition, data on the safety profiles of both products, including immunogenicity and local tolerability at the injection sites, will be collected and compared.

An additional study objective is to identify any potential risk of the transition from Enbrel to GP2015 in terms of general safety and immunogenicity in RA patients

Eligibility criteria: Inclusion Criteria:

* Patients at least 18 years of age with RA diagnosis according to ACR 1987 or ACR/EULAR 20110 criteria \>/= 6 months at the time of baseline visit
* Patient must have active disease defined as DAS28-CRP\>/=3.2
* Patients must have CRP level above ULN \>5mg/l) or erythrocyte sedimentation rate (ESR) \>/=28mm/h
* Patients must have inadequate clinical response to MTX at a dose of 10-25 mg/wk after proper dose escalation according to local standards

Exclusion Criteria:

* Previous exposure to etanercept in the past
* Patients with functional status class IV according to the ACR 1991 revised criteria
* History of active tuberculosis (TB) or Presence of latent (inactive)TB detected by imaging and/or by the QuantiFERON-TB Gold test at screening

Primary outcomes:
measure: Safety: Change in DAS28-CRP Score From Baseline to Week 24 in Patients Treated With GP2015 and Patients Treated With Enbrel
timeFrame: treatment period 1: up to 24 weeks
Secondary outcomes:
measure: Treatment Period 1: Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel
timeFrame: Treatment Period 1, up to 24 weeks
measure: Treatment Period 1 - Safety : Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients
timeFrame: baseline, week 2, week 4, week 12, week 24
measure: Treatment Period 1- DAS28-CRP and DAS28-erythrocyte Sedimentation Rate (ESR) Scores at Baseline and Weeks 4, 12 and 24;
timeFrame: week 4, 12, 24
measure: Treatment Period 1 - Changes From Baseline in DAS28-CRP and DAS-ESR Scores to Weeks 4, 12 and 24
timeFrame: baseline, Week 4, week 12, week 24
measure: Treatment Period 1- Proportion of Patients Achieving EULAR Response
timeFrame: week 4, week 12 and week 24
measure: Treatment Period 1- Proportion of Patients Achieving DAS28 < 2.6 at Weeks 4, 12 and 24
timeFrame: week 4, week 12 and week 24
measure: Treatment Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
timeFrame: week 4, week 12, week 24
measure: Treatment 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: Treatment Period 1- ACR-N Scores at Weeks 4, 12 and 24;
timeFrame: Weeks 4, 12 and 24;
measure: Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by SDAI
timeFrame: Weeks 4, 12 and 24;
measure: Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by CDAI
timeFrame: Weeks 4, 12 and 24;
measure: Treatment Period 1- Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;
timeFrame: Weeks 4, 12 and 24;
measure: Treatment Period 1 - Health Assessment Questionnaire (HAQ) Index at Baseline, Weeks 4, 12 and 24;
timeFrame: Baseline, Weeks 4, 12 and 24;
measure: Treatment Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24;
timeFrame: Baseline, Weeks 4, 12 and 24;
measure: Treatment Period 1 - CRP Levels at Baseline and Weeks 4, 12 and 24
timeFrame: Weeks 4, 12 and 24
measure: Treatment Period 1 - ESR Levels at Baseline and Weeks 4, 12 and 24
timeFrame: Weeks 4, 12 and 24
measure: Treatment Period 2: DAS28-CRP and DAS28-ESR Scores up to Week 48;
timeFrame: Baseline, week 4, week 12, week 24, week 36 and week 48.
measure: Treatment Period 2 : Changes From Baseline in DAS28-CRP and DAS28-ESR Scores From Week 4 up to Week 48
timeFrame: week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2: Proportion of Patients Achieving EULAR Reponse
timeFrame: week 4, week 12, week 24, week 36 and week 48
measure: Treatment Period 2 : Proportion of Patients Achieving DAS28 < 2.6 at Weeks 36 and 48;
timeFrame: week 36 and week 48
measure: Treatment Period 2 : Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria
timeFrame: week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Weeks 36 and 48;
timeFrame: week 36 and week 48
measure: Treatment Period 2 : ACR-N Scores at Weeks 36 and 48;
timeFrame: week 36 and week 48
measure: Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by SDAI
timeFrame: baseline, week 4, week 12, week 24, week 36. week 48
measure: Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by CDAI
timeFrame: baseline, week 4, week 12, week 24, week 36 and week 48
measure: Treatment Period 2 :Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 36 and 48;
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2 :HAQ Index at Weeks 36 and 48;
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 36 and 48;
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2 : CRP Levels at Week 36 and 48
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
measure: Treatment Period 2 : ESR Levels at Week 36 and 48
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
measure: Safety - Overall Study : Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel
timeFrame: up to 48 weeks
measure: Safety : Overall Study: Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients
timeFrame: baseline, week 4, week 12, week 24, week 36, week 48
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: El Cajon
country: United States
facility: Novartis Investigative Site
state: California
city: Upland
country: United States
facility: Novartis Investigative Site
state: California
city: Van Nuys
country: United States
facility: Novartis Investigative Site
state: California
city: Trumbull
country: United States
facility: Novartis Investigative Site
state: Connecticut
city: Clearwater
country: United States
facility: Novartis Investigative Site
state: Florida
city: Gainesville
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Orlando
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: Zephyrhills
country: United States
facility: Novartis Investigative Site
state: Florida
city: Lexington
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Monroe
country: United States
facility: Novartis Investigative Site
state: Louisiana
city: Frederick
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Saint Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Orchard Park
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Rapid City
country: United States
facility: Novartis Investigative Site
state: South Dakota
city: Austin
country: United States
facility: Novartis Investigative Site
state: Texas
city: Carrollton
country: United States
facility: Novartis Investigative Site
state: Texas
city: Spokane
country: United States
facility: Novartis Investigative Site
state: Washington
city: Plovdiv
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Varna
country: Bulgaria
facility: Novartis Investigative Site
city: Pardubice
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 11
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Praha 2
country: Czechia
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Praha 4
country: Czechia
facility: Novartis Investigative Site
city: Zlin
country: Czechia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tallinn
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Bekescsaba
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Szentes
country: Hungary
facility: Novartis Investigative Site
city: Szolnok
country: Hungary
facility: Novartis Investigative Site
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Liepaja
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Klaipeda
country: Lithuania
facility: Novartis Investigative Site
state: Klaipedos Apskritis
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Panevezys
country: Lithuania
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: San Luis Potosi
country: Mexico
facility: Novartis Investigative Site
state: San Luis Potosí
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Santiago De Queretaro
country: Mexico
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
state: Lubelskie
city: Poznan
country: Poland
facility: Novartis Investigative Site
state: Wielkopolskie
city: Elblag
country: Poland
facility: Novartis Investigative Site
city: Nadarzyn
country: Poland
facility: Novartis Investigative Site
city: Warsaw
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Petrozavodsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
city: Smolensk
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Voronezh
country: Russian Federation
facility: Novartis Investigative Site
city: Yaroslavl
country: Russian Federation
facility: Novartis Investigative Site
city: Belgrade
country: Serbia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Poprad
country: Slovakia
facility: Novartis Investigative Site
city: Rimavska Sobota
country: Slovakia
facility: Novartis Investigative Site
city: Zvolen
country: Slovakia
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Cordoba
country: Spain
facility: Novartis Investigative Site
city: Leytonstone
country: United Kingdom
facility: Novartis Investigative Site
state: London
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Global Program Medical Director
name: Arnd Schwebig, MD
role: STUDY_DIRECTOR
References:
citation: Jaworski J, Matucci-Cerinic M, Schulze-Koops H, Buch MH, Kucharz EJ, Allanore Y, Kavanaugh A, Young P, Babic G. Switch from reference etanercept to SDZ ETN, an etanercept biosimilar, does not impact efficacy, safety, and immunogenicity of etanercept in patients with moderate-to-severe rheumatoid arthritis: 48-week results from the phase III, randomized, double-blind EQUIRA study. Arthritis Res Ther. 2019 May 28;21(1):130. doi: 10.1186/s13075-019-1907-x.
citation: Matucci-Cerinic M, Allanore Y, Kavanaugh A, Buch MH, Schulze-Koops H, Kucharz EJ, Woehling H, Babic G, Poetzl J, Davis A, Schwebig A. Efficacy, safety and immunogenicity of GP2015, an etanercept biosimilar, compared with the reference etanercept in patients with moderate-to-severe rheumatoid arthritis: 24-week results from the comparative phase III, randomised, double-blind EQUIRA study. RMD Open. 2018 Nov 14;4(2):e000757. doi: 10.1136/rmdopen-2018-000757. eCollection 2018.