A Study of RoActemra/Actemra (Tocilizumab) in Combination With DMARDs Versus Current Best Practice DMARD Therapy in Patients With Rheumatoid Arthritis

• ClinicalTrials.gov Identifier: NCT01251120
• Recruitment Status: Terminated
• First Posted: December 1, 2010
• Results First Posted: November 11, 2014
• Last Update Posted: November 11, 2014
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This randomized, open-label, parallel-group study will assess the effect on disease remission of RoActemra/Actemra (tocilizumab) in combination with disease-modifying antirheumatic drugs (DMARDs) versus current best practice non-biologic DMARD therapy in patients with moderate-to-severe active rheumatoid arthritis. Patients who are randomly assigned to the RoActemra/Actemra treatment group will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks. The anticipated time on study treatment is 12 months.

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis	Drug: tocilizumab [RoActemra/Actemra]; Drug: DMARD	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Pragmatic, Randomized, Parallel Group Study of the Effect on Disease Remission, Work Productivity and Tolerability of Tocilizumab in Combination With DMARDs and Individually Designed Best Practice DMARD Therapy in Patients With Early, Moderate to Severe Rheumatoid Arthritis
• Study Start Date: November 2011
• Actual Primary Completion Date: January 2013
• Actual Study Completion Date: January 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: tocilizumab [RoActemra/Actemra]; 8 mg/kg intravenously every 4 weeks plus background DMARDs (including methotrexate)
Active Comparator: 2	Drug: DMARD; Non-biologic DMARDs (including methotrexate) according to current best practice

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving Disease Remission at Month 12 Assessed Using the Disease Activity Score Based on 28-Joint Count (DAS28) [ Time Frame: Month 12 ]

   The DAS28 is a combined index for measuring disease activity in Rheumatoid Arthritis (RA). The index includes swollen and tender joint counts (SJC and TJC), acute phase response, and general health status. For this study Erythrocyte sedimentation Rate (ESR) was to be used to calculate DAS28 score. The DAS28, which uses a 28 joint count, is derived from the original DAS which includes a 44 swollen joint count. The DAS28 has been validated in RA. The index is calculated using the following formula:

   DAS28 equals (=) 0.56 times (×) square root of √(TJC) plus (+) 0.28 × √(SJC) + 0.70 × ln(ESR) + 0.014 × GH Where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, ESR measured as millimeters per hour (mm/hr), and GH = general health, which is participant's global assessment of disease activity (100-mm Visual Analog Scale [VAS]). DAS28 less than/equal to (≤) 2.6 defined remission.

Secondary Outcome Measures :

1. Number of Hours Absent From Work [ Time Frame: Baseline and 6 and 12 months ]
   Work productivity measures include absence from work (participant reported and registries), permanent work disability (pension, participant reported and registries), presenteeism (Quantity and Quality instrument, QQ).
2. Percentage of Participants Achieving Disease Remission at Month 6 Assessed Using DAS28 [ Time Frame: Month 6 ]

   The DAS28 is a combined index for measuring disease activity in RA. The index includes SJC and TJC, acute phase response, and general health status. For this study ESR was to be used to calculate DAS28 score. The DAS28, which uses a 28 joint count, is derived from the original DAS which includes a 44 swollen joint count. The DAS28 has been validated in RA. The index is calculated using the following formula:

   DAS28 = 0.56 × √(TJC) + 0.28 × √(SJC) + 0.70 × ln(ESR) + 0.014 × GH Where, TJC28 = tender joint count on 28 joints, SJC28 = swollen joint count on 28 joints, ln = natural log, ESR measured as millimeters per hour (mm/hr), and GH = general health, which is participant's global assessment of disease activity (100-mm VAS). DAS28 ≤ 2.6 defined remission.

3. Percentage of Participants Achieving Responses According to American College of Rheumatology (ACR) Criteria [ Time Frame: Months 6 and 12 ]
   The ACR definition of response includes tender and swollen joint counts, VAS scales for pain, participant and investigator global assessment of disease activity, participant-assessed disability using Health Assessment Questionnaire (HAQ) and acute phase response.
4. Percentage of Participants Achieving Remission at Months 6 and 12 Assessed Using Clinical Activity Disease Index (CDAI) [ Time Frame: Months 6 and 12 ]
   The CDAI is a purely clinical index to measure disease activity. The index includes swollen and tender joint counts, participant global assessment of disease activity, and evaluator global assessment of disease activity (EGA).
5. Change From Baseline to Months 6 and 12 in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) Scores [ Time Frame: Baseline and Months 6 and 12 ]
   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. 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 participants 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 (worse score) to 52 (better score). Clinically relevant improvement is defined as a ≥5-point change from Baseline.
6. Change From Baseline to Months 6 and 12 in European Quality of Life-5D (EQ-5D) Score [ Time Frame: Baseline and Months 6 and 12 ]
   EQ-5D is a participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.
7. Change From Baseline to Months 6 and 12 in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score [ Time Frame: Baseline and Months 6 and 12 ]
   HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Overall score was computed as the sum of the domain scores and divided by the number of domains answered. Total possible score range was 0-3 where 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult patients, over the age of 18 years
• Diagnosis of moderate-to-severe active early rheumatoid arthritis (RA) of less than 2 years duration
• DAS28 >3.2
• Swollen joint count (SJC) >/=6 (66 joint count), and tender joint count (TJC) >/=6 (68 joint count)
• Patients who have received DMARDs (including methotrexate) for 3-7 months

Exclusion Criteria:

• Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months after baseline
• Rheumatic autoimmune disease other than rheumatoid arthritis (secondary Sjögrens syndrome or nodulosis with RA is permitted)
• Functional class III or IV as defined by ACR Classification of Functional Status in Rheumatoid Arthritis
• Prior history of or current inflammatory joint disease other than RA

Contacts and Locations

Locations

Finland

Helsinki, Finland, 00029

Hämeenlinna, Finland, 13530

Jyväskylä, Finland, 40620

Kuopio, Finland, 70101

Riihimäki, Finland, 11101

Rovaniemi, Finland, 96101

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01251120
• Other Study ID Numbers: ML25346
• First Posted: December 1, 2010
• Results First Posted: November 11, 2014
• Last Update Posted: November 11, 2014
• Last Verified: November 2014

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases