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

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01119859
• Other study ID #: WA19924
• Secondary ID: 2009-015845-21
• Status: Completed
• Phase: Phase 4
• First received: April 1, 2010
• Last updated: January 10, 2013
• Start date: May 2010
• Est. completion date: January 2012

Study information

• Verified date: January 2013
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 326
• Est. completion date: January 2012
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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• All disease-modifying anti-rheumatic drugs (DMARD) are to be withdrawn prior to receiving study drug.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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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.
• Adalimumab

• Placebo to tocilizumab

• Placebo to adalimumab

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Czech Republic,  Finland,  Germany,  Greece,  Mexico,  Portugal,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to Week 24 in the Disease Activity Score 28 (DAS28)	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 × v(TJC28)) + (0.28 × v(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).	Baseline to Week 24	No
Secondary	Percentage of Patients With a Remission Response (Disease Activity Score 28 [DAS28] < 2.6) at Week 24	The percentage of patients who achieved remission of their rheumatic arthritis at Week 24, as measured by a DAS28 score < 2.6, is reported.	Week 24	No
Secondary	Percentage of Patients With Low Disease Activity (Disease Activity Score 28 [DAS28] = 3.2) at Week 24	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.	Week 24	No
Secondary	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	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.	Baseline to Week 24	No
Secondary	Percentage of Patients With a European League Against Rheumatism (EULAR) Good Response at Week 24	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.	Baseline to Week 24	No
Secondary	Percentage of Patients With a European League Against Rheumatism (EULAR) Good or Moderate Response at Week 24	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.	Baseline to Week 24	No