Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic and/or Biologic DMARDS

This study has been completed.
Sponsor:
Collaborator:
Clalit Health Services
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01149057
First received: June 22, 2010
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This single arm, open-label study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to non-biologic and/or biologic disease-modifying antirheumatic drugs (DMARDs). Patients will receive intravenous RoActemra/Actemra at a dose of 8 mg/kg every 4 weeks. Anticipated time on study treatment is 96 weeks.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Study to Evaluate the Efficacy and Safety Of Tocilizumab in Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic DMARDs and/or Biologic DMARDs

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 24 in Intent-to-treat (ITT) Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 48 in ITT Population [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 72 in ITT Population [ Time Frame: Baseline, Week 72 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 96 in ITT Population [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 24 in Per Protocol (PP) Population [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 48 in PP Population [ Time Frame: Baseline, Week 48 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 72 in PP Population [ Time Frame: Baseline, Week 72 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).

  • Change From Baseline in FACIT Fatigue Score at Week 96 in PP Population [ Time Frame: Baseline, Week 96 ] [ Designated as safety issue: No ]
    The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. 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-Fatigue score for a total possible score of 0 (worst score) to 52 (best score).


Secondary Outcome Measures:
  • Change From Baseline in Bone Mineral Density (BMD) in Lumbar Spine, Total Hip and Femoral Neck Regions at End of Study [ Time Frame: Baseline, End of the study (up to Week 100) ] [ Designated as safety issue: No ]
    BMD was measured by dual energy X-ray absorptiometry (DXA) and T-scores (a standard deviation [SD] compared with the peak BMD value of an adult aged from 20 to 30 years) were calculated. Osteopenia was defined by a T-score between -1 and -2.5 SD and osteoporosis as a T-score below -2.5 SD, according to the World Health Organization (WHO) guidelines. T-scores for L1-L4 lumbar spine, total spine, total hip (left), and femoral neck (left) were calculated.

  • Number of Participants Achieving Remission According to Disease Activity Score 28 (DAS28) at Weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    Remission was defined as DAS28 score less than (<) 2.6. The DAS28 score was a measure of the participant's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity (visual analog scale [VAS]: 0=no disease activity to 100=maximum disease activity) and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. In case of missing ESR value, C-Reactive Protein (CRP) was used to calculate DAS28. Higher scores represented higher disease activity.

  • Percentage of Participants Achieving Remission According to DAS28 at Weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    Remission was defined as DAS28 score <2.6. The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity.

  • Percentage of Participants With DAS28 Good or Moderate European League Against Rheumatism (EULAR) Response at Weeks 24, 48, 72 and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    The DAS28 score was a measure of the participant's disease activity calculated using the TJC [28 joints], SJC [28 joints], patient's global assessment of disease activity (VAS: 0=no disease activity to 100=maximum disease activity) and the ESR for a total possible score of 0 to approximately 10. In case of missing ESR value, CRP was used to calculate DAS28. Higher scores represented higher disease activity. EULAR Good response: DAS28 ≤3.2 and a change from Baseline <-1.2. EULAR Moderate response: DAS28 greater than (>) 3.2 to less than or equal to (≤) 5.1 or a change from Baseline <-0.6 to greater than or equal to (≥) -1.2.

  • Percentage of Participants Achieving Remission and Low Disease Activity According to Simplified Disease Activity Index (SDAI) at Weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    SDAI was calculated by a simple numerical sum of tender and swollen joint count (based on a 28-joint assessment), patient and physician global assessment of disease activity (VAS 0-10 centimeter [cm]), and level of CRP. SDAI total score 0-86; higher scores = greater effect due to disease activity. Remission was defined as SDAI score ≤3.3. Low disease activity was defined as SDAI score ≤11.0.

  • Percentage of Participants Achieving Remission and Low Disease Activity According to Clinical Disease Activity Index (CDAI) at Weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    CDAI was calculated by a simple numerical sum of tender and swollen joint count (based on 28-joint assessment) and the patient and physician global disease assessment (VAS 0-10 cm). CDAI total score 0-76; higher scores = greater effect due to disease activity. Remission was defined as CDAI score ≤2.8. Low disease activity was defined as CDAI score ≤10.0.

  • Change From Baseline in TJC At Weeks 24, 48, 72, and 96 [ Time Frame: Baseline; Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from baseline indicated improvement.

  • Change From Baseline in SJC At Weeks 24, 48, 72, and 96 [ Time Frame: Baseline; Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from baseline indicated improvement.

  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Response at Weeks 24, 48, 72, and 96 [ Time Frame: Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    ACR20 response: ≥20% improvement in TJC; ≥20% improvement in SJC; and ≥20% improvement in at least 3 of 5 remaining ACR core measures: Patient Assessment of Pain; Patient Global Assessment of Disease Activity (PtGA); Physician Global Assessment of Disease Activity (PGA); self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and either CRP or ESR. ACR50 response required ≥50% improvement in the above criteria and ACR70 response required ≥70% improvement in the above criteria.

  • Change From Baseline in Hemoglobin at Weeks 20, 44, 72 and 96 [ Time Frame: Baseline; Weeks 20, 44, 72 and 96 ] [ Designated as safety issue: No ]
  • C-reactive Protein Level [ Time Frame: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96 ] [ Designated as safety issue: No ]
  • Erythrocyte Sedimentation Rate [ Time Frame: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96 ] [ Designated as safety issue: No ]
  • Participant Assessment of Pain (VAS) [ Time Frame: Baseline; Weeks 8, 16, 24, 36 48, 72 and 96 ] [ Designated as safety issue: No ]
    The mean score of pain as assessed by participants using a 100-mm horizontal VAS, where the left endpoint (0) indicated "No pain," and the right endpoint (100) indicated "Unbearable pain". Higher score indicated higher pain.

  • Change From Baseline in Health Assessment Questionnaire (HAQ) at Weeks 24, 48, 72, and 96 [ Time Frame: Baseline; Weeks 24, 48, 72 and 96 ] [ Designated as safety issue: No ]
    HAQ: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.


Enrollment: 145
Study Start Date: October 2010
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm Drug: tocilizumab [RoActemra/Actemra]
8 mg/kg intravenously, every 4 weeks for 96 weeks

  Eligibility

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

Inclusion Criteria:

  • Adult patients, >/=18 years of age
  • Active moderate to severe rheumatoid arthritis
  • Inadequate response to >/=3 DMARDs (non-biologic and/or biologic)
  • Current treatment at stable dose for >/=8 weeks
  • Etanercept discontinued >/=2 weeks, Anakinra >/=1 week, Infliximab, Adalimumab, Abatacept, Golimumab, Certolizumab >/=4 weeks, prior to baseline visit. Patients have discontinued MabThera/Rituxan or Ocrelizumab >/=16 weeks, and must have proven B-cell repletion

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following baseline
  • Rheumatic autoimmune disease other than RA
  • Functional class IV (American College of Rheumatology Classification)
  • Prior history or current inflammatory joint disease other than RA
  • Oral corticosteroids at a dose of >10 mg/day prednisone equivalent
  • Positive hepatitis B surface antigen (HBsAg) and / or total hepatitis B core antibodies (HBcAb) or hepatitis C virus (HCV) antibody
  • Current or history of recurrent bacterial, viral, fungal or mycobaterial infection
  • History of or currently active primary or secondary immunodeficiency
  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: NCT01149057

Locations
Israel
Afula, Israel, 18101
Ashkelon, Israel, 78306
Beer Sheva, Israel, 8410101
Beer Yaakov, Israel, 6093000
Hadera, Israel, 38100
Haifa, Israel, 3109601
Haifa, Israel, 3339419
Haifa, Israel, 34362
Holon, Israel, 58100
Jerusalem, Israel, 9112001
Jerusalem, Israel, 91240
Kfar Saba, Israel, 44281
Petach Tikva, Israel, 4941492
Ramat Gan, Israel, 5262000
Rehovot, Israel, 76100
Tel Aviv, Israel, 6423906
Sponsors and Collaborators
Hoffmann-La Roche
Clalit Health Services
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01149057     History of Changes
Other Study ID Numbers: ML22873 
Study First Received: June 22, 2010
Results First Received: October 1, 2015
Last Updated: September 1, 2016
Health Authority: Israel: Ministry of Health

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 29, 2016