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Completed

NCT Number: NCT02638259

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

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).

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Novartis Investigative Site, Plovdiv, Bulgaria

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

GP2015

Drug

Enbrel comparator

Primary outcomes

  1. Safety: Change in DAS28-CRP Score From Baseline to Week 24 in Patients Treated With GP2015 and Patients Treated With Enbrel

    Time frame: treatment period 1: up to 24 weeks

    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

Secondary outcomes

  1. Treatment Period 1: Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel

    Time frame: Treatment Period 1, up to 24 weeks

    Frequency of participants with injection site reactions in GP2015 and Enbrel

  2. Treatment Period 1 - Safety : Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients

    Time frame: baseline, week 2, week 4, week 12, week 24

    Frequency of patients having anti-drug antibody (ADA) during 24 weeks (Treatment Period 1) using 1% false positive rate

  3. Treatment Period 1- DAS28-CRP and DAS28-erythrocyte Sedimentation Rate (ESR) Scores at Baseline and Weeks 4, 12 and 24;

    Time frame: week 4, 12, 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

  4. Treatment Period 1 - Changes From Baseline in DAS28-CRP and DAS-ESR Scores to Weeks 4, 12 and 24

    Time frame: baseline, Week 4, week 12, week 24

  5. Treatment Period 1- Proportion of Patients Achieving EULAR Response

    Time frame: week 4, week 12 and week 24

    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) ;

  6. Treatment Period 1- Proportion of Patients Achieving DAS28 < 2.6 at Weeks 4, 12 and 24

    Time frame: week 4, week 12 and week 24

    % patients in DAS28-ESR categories up to week 24

  7. Treatment Period 1- Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria

    Time frame: 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 joints/swollen joints ≤ 1 and CRP (mg/dL) ≤ 1 and patient global assessment (1-10) ≤ 1) at Weeks 4, 12 and 24;

  8. Treatment Period 1- Proportion of Patients Achieving ACR20/50/70 Response at Weeks 4, 12 and 24;

    Time frame: Week 4, week 12 and week 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.

  9. Treatment Period 1- ACR-N Scores at Weeks 4, 12 and 24;

    Time frame: 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.

  10. Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by SDAI

    Time frame: Weeks 4, 12 and 24;

    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.

  11. Treatment Period 1 - Proportion of Patients in Each Disease Activity Category as Defined by CDAI

    Time frame: Weeks 4, 12 and 24;

    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.

  12. Treatment Period 1- Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 4, 12 and 24;

    Time frame: Weeks 4, 12 and 24;

    Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)

  13. Treatment Period 1 - Health Assessment Questionnaire (HAQ) Index at Baseline, Weeks 4, 12 and 24;

    Time frame: Baseline, Weeks 4, 12 and 24;

    Health assessment questionnaire (HAQ) disability index ranges from 0 (best) to 3 (worst)

  14. Treatment Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24;

    Time frame: 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). A score of less than 30 indicates severe fatigue.

  15. Treatment Period 1 - CRP Levels at Baseline and Weeks 4, 12 and 24

    Time frame: Weeks 4, 12 and 24

  16. Treatment Period 1 - ESR Levels at Baseline and Weeks 4, 12 and 24

    Time frame: Weeks 4, 12 and 24

  17. Treatment Period 2: DAS28-CRP and DAS28-ESR Scores up to Week 48;

    Time frame: Baseline, week 4, week 12, week 24, week 36 and 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

  18. Treatment Period 2 : Changes From Baseline in DAS28-CRP and DAS28-ESR Scores From Week 4 up to Week 48

    Time frame: week 4, week 12, week 24, week 36, week 48

  19. Treatment Period 2: Proportion of Patients Achieving EULAR Reponse

    Time frame: week 4, week 12, week 24, week 36 and week 48

    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;

  20. Treatment Period 2 : Proportion of Patients Achieving DAS28 < 2.6 at Weeks 36 and 48;

    Time frame: week 36 and week 48

    percentage of participants in DAS28-ESR categories up to week 48

  21. Treatment Period 2 : Proportion of Patients Achieving EULAR/ACR Boolean Remission Criteria

    Time frame: week 4, week 12, week 24, week 36, week 48

    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;

  22. Treatment Period 2 : Proportion of Patients Achieving ACR20/50/70 Response at Weeks 36 and 48;

    Time frame: week 36 and week 48

  23. Treatment Period 2 : ACR-N Scores at Weeks 36 and 48;

    Time frame: week 36 and week 48

    ACR-N: negative is worsening, positive (up to 100) is an improvement

  24. Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by SDAI

    Time frame: baseline, week 4, week 12, week 24, week 36. week 48

    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.

  25. Treatment Period 2 : Proportion of Patients in Each Disease Activity Category as Defined by CDAI

    Time frame: baseline, week 4, week 12, week 24, week 36 and week 48

    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;

  26. Treatment Period 2 :Proportion of Patients Achieving HAQ Index in Normal Range (≤ 0.5) at Weeks 36 and 48;

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

  27. Treatment Period 2 :HAQ Index at Weeks 36 and 48;

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

    HAQ: from 0 (best) to 3 (worst)

  28. Treatment Period 2 : Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale Relative to Baseline at Weeks 36 and 48;

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

    FACIT: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue

  29. Treatment Period 2 : CRP Levels at Week 36 and 48

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

  30. Treatment Period 2 : ESR Levels at Week 36 and 48

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

  31. Safety - Overall Study : Frequency and Severity of Injection Site Reactions in GP2015 and Enbrel

    Time frame: up to 48 weeks

    Frequency of participants with injection site reactions in GP2015 and Enbrel

  32. Safety : Overall Study: Immunogenicity by Measuring the Rate of Anti-drug Antibody (ADA) Positive Patients

    Time frame: baseline, week 4, week 12, week 24, week 36, week 48

    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

Sponsors and collaborators

Lead sponsor

Sandoz

Industry

Registry information

Official study 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

Acronym: EQUIRA

Important dates

Study start
2015
Primary completion
2016
Study completion
2017
First posted
Dec 23, 2015
Registry last updated
Sep 19, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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