Comparative Efficacy and Safety Study of GP2015 and Enbrel® in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

— EQUIRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02638259
• Other study ID #: GP15-301
• Status: Completed
• Phase: Phase 3
• Start date: February 21, 2015
• Est. completion date: June 12, 2017

Study information

• Verified date: September 2018
• Source: Sandoz
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 376
• Est. completion date: June 12, 2017
• Est. primary completion date: December 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• GP2015
Enbrel comparator

Locations

Country	Name	City	State
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Czechia	Novartis Investigative Site	Pardubice	Czech Republic
Czechia	Novartis Investigative Site	Praha 11	Czech Republic
Czechia	Novartis Investigative Site	Praha 2
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Zlin
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Estonia	Novartis Investigative Site	Tartu
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenchen
Hungary	Novartis Investigative Site	Bekescsaba
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Szentes
Hungary	Novartis Investigative Site	Szolnok
Italy	Novartis Investigative Site	Firenze	FI
Italy	Novartis Investigative Site	Rozzano	MI
Latvia	Novartis Investigative Site	Liepaja
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Klaipeda	Klaipedos Apskritis
Lithuania	Novartis Investigative Site	Panevezys
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Guadalajara	Jalisco
Mexico	Novartis Investigative Site	Merida	Yucatan
Mexico	Novartis Investigative Site	San Luis Potosi	San Luis Potosí
Mexico	Novartis Investigative Site	Santiago De Queretaro
Poland	Novartis Investigative Site	Elblag
Poland	Novartis Investigative Site	Lublin	Lubelskie
Poland	Novartis Investigative Site	Nadarzyn
Poland	Novartis Investigative Site	Poznan	Wielkopolskie
Poland	Novartis Investigative Site	Warsaw
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Petrozavodsk
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	Smolensk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	Voronezh
Russian Federation	Novartis Investigative Site	Yaroslavl
Serbia	Novartis Investigative Site	Belgrade
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Rimavska Sobota
Slovakia	Novartis Investigative Site	Zvolen
Spain	Novartis Investigative Site	Cordoba
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Santiago de Compostela	Galicia
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United Kingdom	Novartis Investigative Site	Edinburgh
United Kingdom	Novartis Investigative Site	Leeds	West Yorkshire
United Kingdom	Novartis Investigative Site	Leytonstone	London
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Austin	Texas
United States	Novartis Investigative Site	Carrollton	Texas
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Cincinnati	Ohio
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigative Site	El Cajon	California
United States	Novartis Investigative Site	Frederick	Maryland
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Lexington	Kentucky
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Monroe	Louisiana
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Orchard Park	New York
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Peoria	Arizona
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Rapid City	South Dakota
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	Spokane	Washington
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Trumbull	Connecticut
United States	Novartis Investigative Site	Upland	California
United States	Novartis Investigative Site	Van Nuys	California
United States	Novartis Investigative Site	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sandoz

Countries where clinical trial is conducted

United States,  Bulgaria,  Czechia,  Estonia,  Germany,  Hungary,  Italy,  Latvia,  Lithuania,  Mexico,  Poland,  Russian Federation,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Change in DAS28-CRP Score From Baseline to Week 24 in Patients Treated With GP2015 and Patients Treated With Enbrel	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, 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 + 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	treatment period 1: up to 24 weeks
Secondary	Treatment Period 1: Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel	Frequency of participants with injection site reactions in GP2015 and Enbrel	Treatment Period 1, up to 24 weeks
Secondary	Treatment Period 1 - Safety : Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients	Frequency of patients having anti-drug antibody (ADA) during 24 weeks (Treatment Period 1) using 1% false positive rate	baseline, week 2, week 4, week 12, week 24
Secondary	Treatment Period 1- DAS28-CRP and DAS28-erythrocyte Sedimentation Rate (ESR) Scores at Baseline and Weeks 4, 12 and 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: best is 0,; < 2.6 - remission,; = 2.6 to = 3.2 - low disease activity; > 3.2 to = 5.1 - moderate disease activity; > 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	week 4, 12, 24
Secondary	Treatment Period 1 - Changes From Baseline in DAS28-CRP and DAS-ESR Scores to Weeks 4, 12 and 24		baseline, Week 4, week 12, week 24
Secondary	Treatment Period 1- Proportion of Patients Achieving EULAR Response	Proportion of patients achieving European League against Rheumatism (EULAR) good response (defined as DAS28 = 3.2 and DAS28 improvement from Baseline > 1.2) and moderate response (defined as DAS28 = 3.2 and DAS28 improvement > 0.6 and = 1.2, or DAS28 > 3.2 and = 5.1 and DAS28 improvement > 0.6 or DAS28 > 5.1 but DAS28 improvement > 1.2) ;	week 4, week 12 and week 24
Secondary	Treatment Period 1- Proportion of Patients Achieving DAS28 < 2.6 at Weeks 4, 12 and 24	% patients in DAS28-ESR categories up to week 24	week 4, week 12 and week 24
Secondary	Treatment Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria	Proportion of patients achieving EULAR/American College of Rheumatology (EULAR/ACR) Boolean remission criteria (defined as number of tender joints/swollen joints = 1 and CRP (mg/dL) = 1 and patient global assessment (1-10) = 1) at Weeks 4, 12 and 24;	week 4, week 12, week 24
Secondary	Treatment Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24;	ACR20 response was defined if a patient fulfilled all 3 criteria below: 20% improvement in tender 68 joint-count; 20% improvement in swollen 68 joint-count; And 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 (HAQ 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.	Week 4, week 12 and week 24
Secondary	Treatment Period 1- ACR-N Scores at Weeks 4, 12 and 24;	ACR-N (American College of Rheumatology percentage of improvement): negative is worsening, positive (up to 100) is an improvement.; ACR-N is a single number that characterizes the percentage of improvement from Baseline that a patient has experienced in analogy to ACR20 described above. ACR-N of X (such as 38) means that the patient had achieved an improvement of at least X% (such as 38%) in tender and swollen joints, and an improvement of at least X% (such as 38%) in 3 of the 5 other parameters mentioned above.	Weeks 4, 12 and 24;
Secondary	Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by SDAI	Proportion of patients in each disease activity category as defined by the Simplified Disease Activity Index (SDAI): high disease activity, SDAI > 26, moderate disease activity, SDAI > 11 to = 26, low disease activity, SDAI > 3.3 to = 11, and remission, SDAI = 3.3 at Weeks 4, 12 and 24; SDAI and CDAI are measures of disease activity in RA. The scores were calculated by numerical summation of the number of tender and swollen joints (using the 28-joint count), and the patient's and physician's global assessment of disease activity.	Weeks 4, 12 and 24;
Secondary	Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by CDAI	Proportion of patients in each disease activity category as defined by the Clinical Disease Activity Index (CDAI): high disease activity, CDAI > 22, moderate disease activity, CDAI > 10 to = 22, low disease activity, CDAI > 2.8 to = 10, and remission, CDAI = 2.8 at Weeks 4, 12 and 24; SDAI and CDAI are measures of disease activity in RA. The scores were calculated by numerical summation of the number of tender and swollen joints (using the 28-joint count), and the patient's and physician's global assessment of disease activity.	Weeks 4, 12 and 24;
Secondary	Treatment Period 1- Proportion of Patients Achieving HAQ Index in Normal Range (= 0.5) at Weeks 4, 12 and 24;	Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)	Weeks 4, 12 and 24;
Secondary	Treatment Period 1 - Health Assessment Questionnaire (HAQ) Index at Baseline, Weeks 4, 12 and 24;	Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)	Baseline, Weeks 4, 12 and 24;
Secondary	Treatment Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at 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). A score of less than 30 indicates severe fatigue.	Baseline, Weeks 4, 12 and 24;
Secondary	Treatment Period 1 - CRP Levels at Baseline and Weeks 4, 12 and 24		Weeks 4, 12 and 24
Secondary	Treatment Period 1 - ESR Levels at Baseline and Weeks 4, 12 and 24		Weeks 4, 12 and 24
Secondary	Treatment Period 2: DAS28-CRP and DAS28-ESR Scores up to Week 48;	DAS28-CRP and DAS28-ESR: best is 0,; < 2.6 - remission,; = 2.6 to = 3.2 - low disease activity; > 3.2 to = 5.1 - moderate disease activity; > 5.1 - high disease activity	Baseline, week 4, week 12, week 24, week 36 and week 48.
Secondary	Treatment Period 2 : Changes From Baseline in DAS28-CRP and DAS28-ESR Scores From Week 4 up to Week 48		week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2: Proportion of Patients Achieving EULAR Reponse	Proportion of patients achieving EULAR good response (defined as DAS28 = 3.2 and DAS28 improvement from Baseline > 1.2) and moderate response (defined as DAS28 = 3.2 and DAS28 improvement > 0.6 and = 1.2, or DAS28 > 3.2 and = 5.1 and DAS28 improvement > 0.6 or DAS28 > 5.1 but DAS28 improvement > 1.2) at Weeks 36 and 48;	week 4, week 12, week 24, week 36 and week 48
Secondary	Treatment Period 2 : Proportion of Patients Achieving DAS28 < 2.6 at Weeks 36 and 48;	percentage of participants in DAS28-ESR categories up to week 48	week 36 and week 48
Secondary	Treatment Period 2 : Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria	Proportion of patients achieving EULAR/ACR Boolean remission criteria (defined as number of tender joints/swollen joints = 1 and CRP (mg/dL) = 1 and patient global assessment (1-10) = 1) at Weeks 36 and 48;	week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Weeks 36 and 48;		week 36 and week 48
Secondary	Treatment Period 2 : ACR-N Scores at Weeks 36 and 48;	ACR-N: negative is worsening, positive (up to 100) is an improvement	week 36 and week 48
Secondary	Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by SDAI	Proportion of patients in each disease activity category as defined by the Simplified Disease Activity Index (SDAI): high disease activity, SDAI > 26, moderate disease activity, SDAI > 11 to = 26, low disease activity, SDAI > 3.3 to = 11, and remission, SDAI = 3.3 at Weeks 36 and 48.	baseline, week 4, week 12, week 24, week 36. week 48
Secondary	Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by CDAI	Proportion of patients in each disease activity category as defined by the Clinical Disease Activity Index (CDAI): high disease activity, CDAI > 22, moderate disease activity, CDAI > 10 to = 22, low disease activity, CDAI > 2.8 to = 10, and remission, CDAI = 2.8 at Weeks 36 and 48;	baseline, week 4, week 12, week 24, week 36 and week 48
Secondary	Treatment Period 2 :Proportion of Patients Achieving HAQ Index in Normal Range (= 0.5) at Weeks 36 and 48;		baseline, week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2 :HAQ Index at Weeks 36 and 48;	HAQ: from 0 (best) to 3 (worst)	baseline, week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 36 and 48;	FACIT: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue	baseline, week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2 : CRP Levels at Week 36 and 48		baseline, week 4, week 12, week 24, week 36, week 48
Secondary	Treatment Period 2 : ESR Levels at Week 36 and 48		baseline, week 4, week 12, week 24, week 36, week 48
Secondary	Safety - Overall Study : Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel	Frequency of participants with injection site reactions in GP2015 and Enbrel	up to 48 weeks
Secondary	Safety : Overall Study: Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients	To assess the immunogenicity of continuous GP2015 treatment versus a treatment transition from Enbrel to GP2015 after 24 weeks of treatment by measuring the rate of ADA positive participants at Weeks 24, 30, 36 and 48. summary of ADA positive data up to week 48 using a 1% false positive cut point	baseline, week 4, week 12, week 24, week 36, week 48