A Study of Tocilizumab (RoActemra/Actemra) Versus Adalimumab in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01119859
First received: April 1, 2010
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

This randomized, blinded, parallel arm study evaluated the efficacy and safety of tocilizumab (RoActemra/Actemra) versus adalimumab as monotherapy in patients with rheumatoid arthritis who are intolerant of methotrexate or where continued treatment with methotrexate was considered inappropriate. Patients were randomized to receive either tocilizumab 8 mg/kg intravenously (iv) every 4 weeks plus placebo subcutaneously (sc) every 2 weeks, or adalimumab 40 mg sc every 2 weeks plus placebo iv every 4 weeks. Treatment was anticipated to last 24 weeks. With regard to the blind, the study nurse was unblinded due to the nature of the treatment administration, but the investigator and the patient remained blinded.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Tocilizumab
Drug: Adalimumab
Drug: Placebo to tocilizumab
Drug: Placebo to adalimumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-center, Randomized, Blinded, Parallel-group Study of the Reduction of Signs and Symptoms During Monotherapy Treatment With Tocilizumab 8 mg/kg Intravenously Versus Adalimumab 40 mg Subcutaneously in Patients With Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28) [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    The DAS28 is a combined index for measuring disease activity in rheumatic arthritis (RA) and includes swollen and tender joint counts, erythrocyte sedimentation rate (ESR), and general health (GH) status. The index is calculated with the following formula: DAS28 = (0.56 × √(TJC28)) + (0.28 × √(SJC28)) + (0.7 × log(ESR)) + (0.014 × GH), where TJC28 = tender joint count and SJC28 = swollen joint count, each on 28 joints. GH = a patient's global assessment of disease activity in the previous 24 hours on a 100 mm visual analog scale (left end = no disease activity [symptom-free and no arthritis symptoms], right end = maximum disease activity [maximum arthritis disease activity]). When ESR equaled 0 mm/hr, it was set to 1 mm/hr. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A negative change score indicates improvement. The analysis was adjusted for stratification factors of duration of RA (≤ 2 years and > 2 years) and region (US and non-US).


Secondary Outcome Measures:
  • Percentage of Patients With a Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients who achieved remission of their rheumatic arthritis at Week 24, as measured by a DAS28 score < 2.6, is reported.

  • Percentage of Patients With Low Disease Activity (Disease Activity Score 28 [DAS28] ≤ 3.2) at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of patients who had low rheumatic arthritis disease activity at Week 24, as measured by a DAS28 score of 3.2 or less, is reported.

  • Percentage of Patients With an Improvement of at Least 20%, 50%, or 70% in American College of Rheumatology (ACR) Score (ACR20/50/70) From Baseline at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Improvement must be seen in tender and swollen joint counts (28 assessed joints) and in at least 3 of the following 5 parameters: Separate patient and physician assessments of patient disease activity in the previous 24 hours on a visual analog scale (VAS, the extreme left end of the line "no disease activity" [symptom-free and no arthritis symptoms] and the extreme right end "maximum disease activity"; patient assessment of pain in previous the 24 hours on a VAS (extreme left end of the line "no pain" and the extreme right end "unbearable pain"); Health Assessment Questionnaire-Disability Index (20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and activities, 0=without difficulty to 3=unable to do); and erythrocyte sedimentation rate.

  • Percentage of Patients With a European League Against Rheumatism (EULAR) Good Response at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2.

  • Percentage of Patients With a European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change of the Disease Activity Score 28 score from baseline was used to determine EULAR responses of good, moderate, or no response. For a post-baseline score ≤ 3.2, a change from baseline of < -1.2 was a good response, < -0.6 to ≥ -1.2 was a moderate response, and ≥ -0.6 was no response. For a post-baseline score > 3.2 to ≤ 5.1, a change from baseline of < -0.6 was a moderate response and ≥ -0.6 was no response. For a post-baseline score > 5.1, a change from baseline < -1.2 was a moderate response and ≥ -1.2 was no response. A good response could not be achieved for post-baseline scores > 3.2.


Enrollment: 326
Study Start Date: May 2010
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tocilizumab 8 mg/kg
Patients received 6 infusions of tocilizumab 8 mg/kg intravenously every 4 weeks and 12 injections of placebo to adalimumab subcutaneously every 2 weeks.
Drug: Tocilizumab
The maximum dose was 800 mg for patients weighing more than 100 kg. Tocilizumab was infused into an arm vein over a 1-hour period.
Other Names:
  • RoActemra
  • Actemra
Drug: Placebo to adalimumab
Active Comparator: Adalimumab 40 mg
Patients received 12 injections of adalimumab 40 mg subcutaneously every 2 weeks and 6 infusions of placebo to tocilizumab intravenously every 4 weeks.
Drug: Adalimumab Drug: Placebo to tocilizumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, ≥ 18 years of age.
  • Rheumatoid arthritis of > 6 months duration.
  • Intolerant of methotrexate or continued treatment with methotrexate is considered inappropriate.
  • All disease-modifying anti-rheumatic drugs (DMARD) are to be withdrawn prior to receiving study drug.
  • Weight ≤ 150 kg.

Exclusion Criteria:

  • Major surgery (including joint surgery) within 12 weeks prior to baseline or planned major surgery within 6 months after baseline.
  • History of or current inflammatory joint disease other than rheumatoid arthritis (RA).
  • Treatment with a biologic agent at any time prior to baseline.
  • Intra-articular or parenteral corticosteroids ≤ 4 weeks prior to baseline.
  • Active current infection or history of recurrent bacterial, viral, fungal or mycobacterial infection.
  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: NCT01119859

  Show 82 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01119859     History of Changes
Other Study ID Numbers: WA19924, 2009-015845-21
Study First Received: April 1, 2010
Results First Received: September 18, 2012
Last Updated: January 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on July 29, 2014