Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)

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: NCT01219933
Recruitment Status : Completed
First Posted : October 13, 2010
Results First Posted : January 19, 2015
Last Update Posted : January 19, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 11, 2010
First Posted Date  ICMJE October 13, 2010
Results First Submitted Date  ICMJE August 26, 2014
Results First Posted Date  ICMJE January 19, 2015
Last Update Posted Date January 19, 2015
Study Start Date  ICMJE January 2011
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • Median GC Dose Taken During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    During the noninterventional phase of the study participants received GC as prescribed by the physician. Doses of all GC administered are expressed as MP equivalents.
  • Number of Participants With GC Switches During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    During the noninterventional phase of the study, once LDA was achieved, GC was switched to MP tablets.
  • Type of GC Taken at the End of the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    During the noninterventional phase of the study participants received GC as prescribed by the physician.
  • Percentage of Participants in the Interventional Phase Who Achieved LDA and Discontinued Oral GC Within 20 Weeks [ Time Frame: Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), and 8 (12 months) ]
    The percentage of participants with rheumatoid arthritis (RA) with LDA was defined as DAS28 ≤3.2, able to discontinue oral GC within 20 weeks and at the latest at V8, confirmed at the Consolidation Visit without loss of clinical response defined as DAS28 (CRP) >3.2.
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2010)
  • Non-interventional phase: Assessment/documentation of glucocorticoid treatment in clinical daily practice [ Time Frame: 6 months ]
  • Interventional phase: Proportion of patients in low disease activity able to discontinue oral glucocorticoids within 20 weeks and at the latest at Visit 8 without loss of clinical response defined as Disease Activity Score (DAS28) >3.2 [ Time Frame: 20 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2015)
  • Percentage of Participants Able to Acheive LDA Assessed Using DAS28 While Receiving Oral GC on Background Tocilizumab Treatment During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and Patient's Global Assessment (PtGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day= LDA.
  • Percentage of Participants Acheiving Remission Assessed Using DAS28 While Receiving Oral GC on Background TocilizumabTreatment During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28 <2.6 = remission.
  • Percentage of Participants With Erosions During the NonInterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    In RA, the presence, number and size of bone erosions and the number of joints with erosions on conventional radiographs (CRs) are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
  • Number of Erosions During the NonInterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    In RA, the presence, number, and size of bone erosions and the number of joints with erosions on CRs are hallmarks for diagnosis, staging and prediction of damage progression and are used for treatment monitoring in randomized controlled studies.
  • Percentage of Participants Positive for Rheumatoid Factor (RF) During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    RF is the auto antibody directed against immunoglobulin G (IgG) and its concentration is observed in human serum or plasma. RF value higher than 20 units per milliliter (U/mL) is considered positive.
  • Percentage of Participants Positive for Anti-cyclic Citrullinated Peptide (Anti-CCP) Antibody During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    Anti-CCP antibodies are important markers of bone erosion in RA. Anti-CCP antibodies were classified as positive if >7 U/mL.
  • Health Assessment Questionnaire Disability Index (HAQ-DI) During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. Timepoint was V2, or before V2 for participants withdrawn before V2.
  • DAS28-CRP During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    DAS28-CRP was calculated from the swollen joint count (SJC) and tender joint count (TJC) using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-CRP values indicated in the Case Report Form (CRF) were recalculated by the data manager. The recalculated values were used in the statistical analyses.
  • DAS28-ESR During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    DAS28-ESR was calculated from the SJC and TJC using the 28 joints count and ESR (millimeters per hour [mm/hr]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-ESR ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-ESR <2.6=remission. Timepoint was V2, or before V2 for participants withdrawn before V2; DAS28-ESR values indicated in the CRF were recalculated by the data manager. The recalculated values were used in the statistical analyses.
  • Clinical Disease Activity Index (CDAI) During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and Physician Global Assessment (PGA) of disease assessed on 0-100 mm Visual analog scale (VAS); higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity.
  • Median Time Interval Between V1 and V2 [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    The noninterventional phase was planned to last for a maximum of 6 months per participant. The time between V1 and V2 was measured in months.
  • Median Dose of Tocilizumab During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
  • Number of Participants With Changes in Tocilizumab Dose During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
    The dose of tocilizumab could have been reduced from the recommended 8 mg/kg to 4 mg/kg in participants in the case of adverse events.
  • Percentage of Participants With Changes in RA Treatment During the Noninterventional Phase [ Time Frame: V1 and V2 (up to 6 months after V1) ]
  • Percentage of Participants Able to Start the GC Reduction Phase at V3 [ Time Frame: V3 (7 months) ]
    All participants who maintained LDA (defined as DAS28-CRP ≤3.2) from V2 to V3 were included in the interventional phase for reduction of GC.
  • Percentage of Participants Able to Reduce Oral GCs by ≥50 Percent (%) During the Interventional Phase by V9 [ Time Frame: V9 (24 weeks after V3) ]
  • Percentage of Participants Able to Discontinue GCs During the Interventional Phase by V9 [ Time Frame: V9 (24 weeks after V3) ]
  • Time-Averaged GC Dose Changes During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    Area Under the Curve (AUC) of GC dose during the interventional phase was determined using the trapezoidal method and was calculated as: AUC = sigma(Ti+1 - Ti) x [(Di+1+Di)/2] With Di=dosage at time Ti It corresponds to the total GC dose received between Baseline (visit 3) and visit 9 and has been calculated only for the 30 patients achieving visit 9.
  • DAS28-CRP During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    DAS28-CRP was calculated from the SJC and TJC using the 28-joint count and CRP (mg/L). Total score range: 0 to 10, higher score indicated more disease activity. DAS28-CRP) ≤3.2=LDA and >3.2 to 5.1=moderate to high disease activity, and DAS28-CRP <2.6=remission. DAS28-CRP values indicated in the CRF were recalculated by the data manager. The cumulative DAS28 (CRP) value (AUC method) was performed using the calculated DAS28. The recalculated values were used in the statistical analyses.
  • HAQ-DI During the Interventional Phase [ Time Frame: Visit 3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    HAQ-DI is a self-reported, valid assessment of functional disability in RA. Assessed based on ability of participants to perform daily activities in 8 categories: dressing, arising, eating, walking, reaching, gripping, hygiene, and carrying out daily activities. HAQ-DI score range: 0-3: without any difficulty=0, with some difficulty=1, with much difficulty=2, unable to do=3. HAQ total scores expressed as overall mean score with range 0-3: 0-0.25=normal functioning; 0.25-0.5=mild functional limitation; 0.5-1=moderate functional limitation; more than 1=significant functional limitation. V3, CV, and the change from V3 to CV was determined.
  • VAS-Physician's Global Assessment of Disease Activity (GDA) During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    Physician's were asked to determine the overall GDA for each participant using a 100-mm VAS, where 0=no disease activity and 100=maximum disease activity. The physician marked the line corresponding to their assessment and the distance from the left edge was measured. V3, CV, and the change from V3 to CV was determined.
  • VAS for Pain (VAS-Pain) During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    Participants were asked to mark the line corresponding to the intensity of their pain on a 100-mm VAS, where 0=no pain and 100=worst possible pain. The distance from the left edge was measured. Change = V3 mean minus CV mean.
  • SJC and TJC During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    TJC and SJC were assessed for 28 joints. An assessment of 28 joints for swelling and tenderness was made. Joints were assessed and classified as swollen (1)/not swollen (0) and tender (1)/not tender (0) by pressure and joint manipulation on physical examination for a total score range of 0-28. Higher scores indicated greater disease activity (tenderness/swelling). V3, CV, and the change from V3 to CV was determined.
  • Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-F score for a total possible score of 0 (worse score) to 52 (better score). V3, CV, and the change from V3 to CV was determined.
  • Short-Form 36 (SF-36) Mental Component Score (MCS) and Physical Component Score (PCS) During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
  • SF-36 Subscale Scores During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component scores (PCS and MCS). Total of 11 variables were analyzed (8 subscales, 2 composite subscales and Question 2 "how would you rate your health in general now?" (range 1= better, 5= worst). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Higher scores reflect higher quality of life. V3, CV, and the change from V3 to CV was determined.
  • CDAI Score During the Interventional Phase [ Time Frame: V3 (7 months) and CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission, >2.8 to 10=LDA, >10 to 22=moderate disease activity, and >22=high disease activity. V3, CV, and the change from V3 to CV was determined.
  • Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using CDAI [ Time Frame: Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), and 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    The CDAI is the numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PtGA and PGA assessed on 0-100 mm VAS; higher scores=greater affection due to disease activity. CDAI total score=0-76. CDAI ≤2.8=disease remission and >2.8 to 10=LDA.
  • Percentage of Participants With LDA or Remission During the Interventional Phase Assessed Using DAS28-CRP [ Time Frame: Visits 3 (7 months), 4 (8 months), 5 (9 months), 6 (10 months), 7 (11 months), 8 (12 months), 9 (24 weeks after V3) or CV (4 weeks after GC-free status, maximum of 24 weeks after V3) ]
    DAS28 calculated from the number of swollen joints (SJC) and tender joints (TJC) using the 28 joint count, the CRP and PtGA of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). DAS28-CRP ≤3.2 and oral GC intake with MP equivalent dose of ≥1 mg and ≤20 mg/day=LDA; DAS28 <2.6 = remission.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2010)
  • Non-interventional phase: Proportion of patients able to reach low disease activity defined as Disease Activity Score (DAS28) </=3.2 [ Time Frame: 6 months ]
  • Non-interventional phase: Proportion of patients able to remission defined as Disease Activity Score (DAS28) <2.6 [ Time Frame: 6 months ]
  • Non-interventional phase: Description of the management of patients in the period evolving towards low disease activity [ Time Frame: 6 months ]
  • Interventional phase: Proportion of patients able to start the step down scheme for glucocorticoids [ Time Frame: Week 1 ]
  • Interventional phase: Proportion of patients able to reduce oral glucocorticoids (>/=50%) [ Time Frame: Week 24 ]
  • Interventional phase: Proportion of patients able to discontinue glucocorticoids by week 24 [ Time Frame: Week 24 ]
  • Interventional phase: Change in mean Health Assessment Questionnaire [ Time Frame: Week 24 ]
  • Interventional phase: Change in mean physicians global assessment according to Disease Activity Score (DAS28) [ Time Frame: Week 24 ]
  • Interventional phase: Change in mean Visual Analogue Scale pain [ Time Frame: Week 24 ]
  • Interventional phase: Change in mean Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue [ Time Frame: Week 24 ]
  • Interventional phase: Change in mean Short Form (36) Health Survey score [ Time Frame: Week 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Glucocorticoid Use to Evaluate Systematic Methylprednisolone Reduction in Patients With Rheumatoid Arthritis on Background RoActemra/Actemra (Tocilizumab) (ACT-ALONE)
Official Title  ICMJE An Open-label, Single-arm Study to Describe Glucocorticoid Use in Rheumatoid Arthritis Patients Treated With Tocilizumab in Daily Clinical Practice and to Evaluate Systematic Glucocorticoid Dose Reduction Once Low Disease Activity is Reached (ACT-ALONE)
Brief Summary This open-label, single-arm study will assess the use of glucocorticoids (GC) in daily clinical practice and will evaluate the dose reduction of glucocorticoids once low disease activity is achieved in patients with rheumatoid arthritis tre ated with GC and background RoActemra/Actemra (tocilizumab) 8mg/kg intravenously every 4 weeks. In the non-interventional phase, the use of GC in daily clinical Belgian practice will be evaluated and described. This period of maximum 6 mont hs will allow those patients to obtain the inclusion criteria for the secondary interventional phase. In the interventional phase, a systematic GC dose reductio n schedule will be evaluated in patients having achieved low disease activity wh ile receiving the same background therapy with RoActemra/Actemra 8 mg/kg. Methyl prednisolone will be given from a starting dose of >/= 1 mg to </=20 mg orally d aily and will be tapered down. The anticipated study duration is up to 13 months
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rheumatoid Arthritis
Intervention  ICMJE
  • Drug: methylprednisolone
    starting dose >/= 1 mg and </= 20 mg orally daily, according to dose-reduction schedule
  • Drug: tocilizumab [RoActemra/Actemra]
    background therapy: 8 mg/kg iv every 4 weeks
Study Arms  ICMJE Experimental: 1
Interventions:
  • Drug: methylprednisolone
  • Drug: tocilizumab [RoActemra/Actemra]
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2015)
68
Original Estimated Enrollment  ICMJE
 (submitted: October 11, 2010)
120
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date March 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Non-interventional phase

  • Adult patients, >/=18 years of age
  • Moderate to severe active rheumatoid arthritis defined as Disease Activity Score using 28-joint count (DAS28) >/=5.1
  • Patients with inadequate clinical response to a current treatment with 2 or more non-biologic disease-modifying anti-rheumatic drugs (DMARDs), one of them being methotrexate (MTX) optimally administered during a period of more than 3 months or inadequate response to a current anti-TNF therapy
  • Current use of oral glucocorticoids started at least 4 weeks prior to enrolment Interventional phase
  • Patients enrolled in the non-interventional phase
  • Patients with low disease activity defined as DAS28 </=3.2 at Visit 2
  • Use of oral glucocorticoids with methylprednisolone equivalent dose of >/=1mg and </=20mg/day at Visit 2

Exclusion Criteria:

Non-interventional & interventional phase

  • Rheumatic autoimmune disease other than rheumatoid arthritis, or significant systemic involvement secondary to rheumatoid arthritis
  • Functional class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in rheumatoid arthritis
  • Prior history or current inflammatory joint disease other than rheumatoid arthritis (e.g. gout)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01219933
Other Study ID Numbers  ICMJE ML25252
2010-019694-15
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP