A Study of Tocilizumab as Monotherapy or in Combination With DMARDs in Patients With Moderate to Severe Active Rheumatoid Arthritis

Multicenter, Open-Label Study to Evaluate the Safety, Tolerability and the Effect on Disease Activity of Tocilizumab in Patients With Active Rheumatoid Arthritis on Background Non-biologic DMARDs Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti- TNF Therapy.

This open-label single-arm study will evaluate the safety, tolerability and efficacy of tocilizumab [RoActemra/Actemra] in patients with moderate to severe rheumatoid arthritis who experience an inadequate clinical response to a stable dose of non-biologic disease modifying anti-rheumatic drugs (DMARD) or anti-tumor necrosis factors (TNFs). RoActemra/Actemra will be administered as a monotherapy or in combination with DMARDs. RoActemra/Actemra will be administered as intravenous infusion at a dose of 8 mg/kg every 4 weeks for a total of 6 infusions. The anticipated time on study treatment is 24 weeks. The target sample size is 50-150 patients.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab [RoActemra/Actemra]

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bahrain
  • Manama, Bahrain, 12
  • Riffa, Bahrain, 28743
• Iran, Islamic Republic of
  • Isfahan, Iran, Islamic Republic of, 8174675731
  • Tehran, Iran, Islamic Republic of, 1333631151
  • Tehran, Iran, Islamic Republic of, 14114
• Kuwait
  • Safat, Kuwait, 13041
• Qatar
  • Doha, Qatar, 3050
• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
  • Abu Dhabi, United Arab Emirates, 51900

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, >/=18 years of age
• moderate to severe rheumatoid arthritis (DAS28 >3.2) of 6 months duration
• inadequate clinical response to non-biologic DMARDs or anti-TNF
• bodyweight </=150 kg

Exclusion Criteria:

• rheumatic autoimmune disease or inflammatory joint disease other than RA
• major surgery within 8 weeks prior to screening or planned major surgery within 6 months following screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1	Drug: tocilizumab [RoActemra/Actemra]; 8 mg/kg iv infusion, every 4 weeks for a total of 6 infusions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Reporting Any Adverse Event - Overall Summary of Events	Percentage of participants with a serious adverse event (SAE), who died, with an adverse event (AE), or study drug related AE during the study.	Baseline and Weeks 2, 4, 8, 12, 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants by Disease Activity Score Based on 28-Joint Count (DAS28) Category	DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm Visual analog scale - VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. A DAS28 score of greater than (>)5.1 indicated high disease activity, a score of >3.2 but less than or equal to (≤)5.1 indicated moderate disease activity, a score of greater than or equal to (≥)2.6 but ≤3.2 indicated low disease activity, and a score of less than <2.6 indicated disease remission. Week 24 is the Follow-Up visit.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving a Clinically Meaningful Improvement as Measured by DAS28	DAS28 was calculated from the number of swollen joints and tender joints using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Participants achieved a clinically meaningful improvement in DAS28 if there was a reduction of at least 1.2 units from baseline.	Weeks 4, 8, 12, 16, 20, and 24
Time to DAS28 Response by DAS28 Category	Time to response is the number of days from date of first infusion to date of event. DAS28 response was defined as achievement of Low Disease Activity (DAS28 ≥2.6 to ≤3.2), Remission (DAS28 <2.6), or Clinically Meaningful Improvement (change of >1.2 from baseline).	Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) of at Least 0.22 Units	HAQ 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. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.	Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants With Improvement in Physical Function by HAQ-DI Category	Physical function scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3. The HAQ-DI score at every visit was categorized into none to mild disability (HAQ-DI <1), moderate disability (1≤ HAQ-DI <2) and severe disability (HAQ-DI ≥2). The percentages of the participants falling in each of these categories with respect to the visits were determined.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
HAQ-DI Score by Visit	HAQ 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. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3..	Baseline and Weeks 4, 8, 12, 16, 20, and 24
C-Reactive Protein (CRP) Values by Study Visit	CRP is an acute phase inflammatory marker. The serum concentration of CRP is measured in milligrams per liter (mg/L). A reduction in the level is considered an improvement.	Baseline and Weeks 4, 8, 12, 16, 20, and 24
Erythrocyte Sedimentation Rate	ESR (measured in mm/hr) is an inflammation marker used to determine acute phase response.	Baseline and Weeks 4, 8, 12, 16, 20, and 24

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: March 8, 2010
• First Submitted That Met QC Criteria: March 17, 2010
• First Posted (ESTIMATE): March 18, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): July 22, 2014
• Last Update Submitted That Met QC Criteria: June 23, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML22440