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

Rheumatoid Arthritis Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01089023
• Other study ID #: ML22440
• Status: Completed
• Phase: Phase 4
• First received: March 8, 2010
• Last updated: June 23, 2014
• Start date: January 2010
• Est. completion date: December 2011

Study information

• Verified date: June 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: Qatar: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• tocilizumab [RoActemra/Actemra]
8 mg/kg iv infusion, every 4 weeks for a total of 6 infusions

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Bahrain,  Iran, Islamic Republic of,  Kuwait,  Qatar,  United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No