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Trial record 1 of 1 for:    ADMYRA
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Clinical Trial to Compare Treatment With GP2017 and Humira® in Patients With Rheumatoid Arthritis (ADMYRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02744755
Recruitment Status : Completed
First Posted : April 20, 2016
Results First Posted : December 19, 2018
Last Update Posted : December 19, 2018
Sponsor:
Collaborator:
Hexal AG
Information provided by (Responsible Party):
Sandoz

Brief Summary:
Clinical trial to compare treatment with GP2017 and Humira® in patients with Rheumatoid Arthritis

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Biological: Adalimumab - GP2017 Biological: Adalimumab - US licensed Humira Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 353 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : March 31, 2016
Actual Primary Completion Date : January 31, 2017
Actual Study Completion Date : September 26, 2017

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: 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).
Biological: Adalimumab - GP2017
Adalimumab - GP2017
Other Name: GP2017

Active Comparator: 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).
Biological: Adalimumab - US licensed Humira
Adalimumab - US licensed Humira
Other Name: Humira - Comparator




Primary Outcome Measures :
  1. Study Period 1: Change in DAS28-CRP Score From Baseline at Week 12 in Patients Treated With GP2017 and Patients Treated With Humira [ Time Frame: 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 :
  1. Study Period 1: Time-weighted Averaged Change From Baseline in DAS28-CRP Until Week 24 in Patients Treated With GP2017 and With Humira [ Time Frame: 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

  2. Study Period 1- Proportion of Patients Achieving EULAR Criterion for Remission [ Time Frame: week 4, week 12 and week 24 ]
    Proportion of patients achieving European League against Rheumatism (EULAR) remission (defined as DAS28 CRP < 2.6 )

  3. Study Period 1- Proportion of Patients Achieving EULAR Criterion for Good 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 at post-baseline assessment timepoint(s) with an improvement of >1.2 in DAS28 from baseline.)

  4. Study Period 1- Proportion of Patients Achieving EULAR Criterion for Moderate Response [ Time Frame: 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) ;

  5. Study 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 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).

  6. 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 [ Time Frame: 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.


  7. Study 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: -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.


  8. Study Period 1 - Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI©) at Weeks 4, 12 and 24; [ Time Frame: 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.


  9. Study Period 1- Proportion of Patients Achieving HAQ-DI© in Normal Range (≤ 0.5) at Weeks 4, 12 and 24; [ Time Frame: Weeks 4, 12 and 24; ]
    Health assessment questionnaire disability index (HAQ-DI©) ranges from 0 (best) to 3 (worst)

  10. Study Period 1- Proportion of Patients Achieving HAQ-DI© Score Improvement >0.3 at Weeks 4, 12 and 24 [ Time Frame: Weeks 4, 12 and 24; ]
    Health assessment questionnaire (HAQ-DI©) disability index ranges from 0 (best) to 3 (worst)

  11. Study Period 1 - Functional Assessment of Chronic Illness Therapy (FACIT©) Fatigue Scale Relative to Baseline at Weeks 4, 12 and 24 (Change From Baseline) [ Time Frame: 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).

  12. Study Period 1 - CRP (C-reactive Protein) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 [ Time Frame: 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)

  13. Study Period 1 -ESR (Erythrocyte Sedimentation Rate) Changes From Baseline in GP2017 and US-licensed Humira Treated at Weeks 4, 12 and 24 [ Time Frame: 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)

  14. Study Period 1: Incidence and Severity of Injection Site Reactions in GP2017 and Humira [ Time Frame: Treatment Period 1, 24 weeks ]
    Incidence of injection site reactions in GP2017 and Humira

  15. 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) [ Time Frame: baseline, week 2, week 4, week 12, week 24 ]
    Frequency of patients having anti-drug antibody (ADA) during 24 weeks

  16. 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) [ Time Frame: week 24, week 36, week 48 ]
    Frequency of patients having anti-drug antibody (ADA) during 24 weeks

  17. 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 [ Time Frame: week 48 ]
  18. 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 [ Time Frame: Weeks 48 ]
    Health assessment questionnaire (HAQ-DI) disability index ranges from 0 (best) to 3 (worst)

  19. 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 [ Time Frame: week 48 ]
  20. 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 [ Time Frame: week 48 ]
    FACIT©: from 0 (worst) to 52 (best), a score of less than 30 indicates severe fatigue

  21. 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 [ Time Frame: 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.


  22. Study Period 2: Incidence of Injection Site Reactions in Patients Treated Continuously With GP2017 and in Patients Treated With GP2017 After Switch From Humira [ Time Frame: up to 48 weeks ]
    Incidence of injection site reactions



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02744755


Locations
Show Show 83 study locations
Sponsors and Collaborators
Sandoz
Hexal AG
  Study Documents (Full-Text)

Documents provided by Sandoz:
Study Protocol  [PDF] February 1, 2017
Statistical Analysis Plan  [PDF] March 19, 2018

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Responsible Party: Sandoz
ClinicalTrials.gov Identifier: NCT02744755    
Other Study ID Numbers: GP17-302
2015-003433-10 ( EudraCT Number )
First Posted: April 20, 2016    Key Record Dates
Results First Posted: December 19, 2018
Last Update Posted: December 19, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents