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Trial record 2 of 17 for:    CONCERTO

Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA) (CONCERTO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01185301
First received: August 18, 2010
Last updated: September 11, 2013
Last verified: September 2013
  Purpose
The purpose of this study is to determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).

Condition Intervention Phase
Early Rheumatoid Arthritis
Biological: adalimumab
Drug: methotrexate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Parallel-Arm, Multicenter Study to Determine the Dose Response of Methotrexate (MTX) in Combination Therapy With Adalimumab in Subjects With Early Rheumatoid Arthritis (CONCERTO)

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Percentage of participants achieving low disease activity as defined by a clinical response (DAS28[CRP] < 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.


Secondary Outcome Measures:
  • Percentage of Participants With DAS28(CRP) Remission at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    Disease remission was defined as a disease activity score, based on CRP, for 28 joints that was < 2.6 (DAS28[CRP] < 2.6). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10.

  • Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

    Response, as defined by ACR 20 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Disability Index of the Health Assessment Questionnaire
    • Acute phase reactant value (C-reactive protein).

  • Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

    Response, as defined by ACR 50 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Disability Index of the Health Assessment Questionnaire
    • Acute phase reactant value (C-reactive protein).

  • Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

    Response, as defined by ACR 70 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 70% improvement in tender joint count; ≥ 70% improvement in swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Disability Index of the Health Assessment Questionnaire
    • Acute phase reactant value (C-reactive protein).

  • Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

    Response, as defined by ACR 90 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Disability Index of the Health Assessment Questionnaire
    • Acute phase reactant value (C-reactive protein).

  • Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]

    Response, as defined by ACR 100 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 100% improvement in tender joint count; ≥ 100% improvement in swollen joint count; and ≥ 100% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Disability Index of the Health Assessment Questionnaire
    • Acute phase reactant value (C-reactive protein).

  • Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.

  • Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ -0.22 at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is a change from Baseline of ≥ 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.

  • Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    The modified Total Sharp Score (mTSS) is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  • Percentage of Participants With No Radiographic Progression at Week 26 [ Time Frame: Baseline, Week 26 ] [ Designated as safety issue: No ]
    "No radiographic progression" was defined as a change from Baseline in modified Total Sharp Score (mTSS) at Week 26 of ≤ 0.5. mTSS is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  • Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    SDAI is a measure of disease activity derived as follows: SDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) + CRP (mg/dL), where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]), and CRP is C-reactive protein measured in mg/dL. SDAI total score = 0 to 86. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.

  • Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26 [ Time Frame: Week 26 ] [ Designated as safety issue: No ]
    CDAI is a measure of disease activity derived as follows: CDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]). CDAI total score = 0 to 76. CDAI ≤ 2.8 indicates disease remission, > 2.8 to 10 = low disease activity, > 10 to 22 = moderate disease activity, and > 22 = high disease activity.


Enrollment: 395
Study Start Date: October 2010
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ADA + 2.5 mg MTX
2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks
Biological: adalimumab
Pre-filled syringe every other week
Other Name: Humira
Drug: methotrexate
weekly oral capsule dosing
Active Comparator: ADA + 5 mg MTX
5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
Biological: adalimumab
Pre-filled syringe every other week
Other Name: Humira
Drug: methotrexate
weekly oral capsule dosing
Active Comparator: ADA + 10 mg MTX
10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks
Biological: adalimumab
Pre-filled syringe every other week
Other Name: Humira
Drug: methotrexate
weekly oral capsule dosing
Active Comparator: ADA + 20 mg MTX
MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Biological: adalimumab
Pre-filled syringe every other week
Other Name: Humira
Drug: methotrexate
weekly oral capsule dosing

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects at least 18 years of age
  • Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider
  • Subject must meet the following criteria:

    1. Disease Activity Score of C-reactive Protein (DAS28[CRP]) ≥ 3.2 (at the Baseline visit only)
    2. At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)
    3. At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)
    4. C-reactive protein (CRP) ≥ 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) ≥ 28 mm/1h (at the Screening and Baseline visits)
    5. Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive
  • Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening

Exclusion Criteria:

  • Subject has previous exposure to any systemic biologic therapy including adalimumab
  • Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)
  • Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)
  • Subject has chronic arthritis diagnosed before age 17 years
  • History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)
  • Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test
  • Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit
  • Female subject who is pregnant or breast-feeding or considering becoming pregnant
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01185301

  Show 68 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Dawn Carlson, MD AbbVie
  More Information

Additional Information:
Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT01185301     History of Changes
Other Study ID Numbers: M12-073  2010-019514-24 
Study First Received: August 18, 2010
Results First Received: September 11, 2013
Last Updated: September 11, 2013
Health Authority: United States: Food and Drug Administration
Germany: Paul-Ehrlich-Institut
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Canada: Health Canada
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicinal Products and Health Products
Spain: Ministry of Health

Keywords provided by AbbVie:
Arthritis
Erosion
Humira
Adalimumab
Injection
Rheumatoid
Methotrexate

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on September 29, 2016