A Study of RoActemra/Actemra (Tocilizumab) in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to DMARDs or Anti-TNF

NCT01326962 | Completed Phase 3 Results

• 1 other identifier: ML22726
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 4

Brief Summary

This open-label, single arm study will evaluate the safety and efficacy of RoActemra/Actemra (tocilizumab) in patients with active, moderate to severe rheumatoid arthritis who have an inadequate response to disease-modifying antirheumatic drugs (DMARDs) or anti-TNF. Patients will receive RoActemra/Actemra at a dose of 8 mg/kg (max 800 mg) intravenously every 4 weeks for a total of 6 infusions. Non-biologic DMARD therapy may be continued throughout the study. Anticipated time on study treatment is 24 weeks.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (8)

• Disease Activity as Measured by Disease Activity Score 28 (DAS28)

  The DAS28 is a combined index for measuring disease activity in rheumatoid arthritis (RA). The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (erythrocyte sedimentation rate \[ESR\] in millimeters per hour \[mm/hr\]), and general health status (participant global assessment of disease activity using visual analog scale \[VAS\], range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

  Up to 1 year

• Number of Participants Who Achieved Remission (DAS28 < 2.6)

  The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

  Up to 1 year

• Time to Das28 Remission

  Time to DAS28 Remission was the Time in days from the first infusion of study drug to the achievement of a DAS28 score \< 2.6 units. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

  Up to 1 year

• Number of Participants Who Achieved a Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units)

  DAS28 Clinically Significant Improvement was defined as a DAS28 score reduction of at least 1.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

  Up to 1 year

• Number of Participants Who Achieved Low Disease Activity (DAS28 < 3.2)

  DAS28 low disease activity was defined as a DAS28 score reduction of at least 3.2 units from Baseline. The DAS28 is a combined index for measuring disease activity in RA. The index includes swollen (range 0-28) and tender (range 0-28) joint counts, acute phase response (ESR in mm/hr), and general health status (participant global assessment of disease activity using VAS, range 1-100 mm). DAS28, which uses a 28-joint count, is derived from the original DAS, which includes a 44-swollen joint count. The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity.

  Up to 1 year

• Number of Participants Who Achieved Clinically Meaningful Health Assessment Questionnaire Response

  Health Assessment Questionnaire (HAQ) is a self-completed participant questionnaire specific for Rheumatoid Arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. To calculate HAQ, the participant must have a domain score for at least 6 out of 8 domains. The HAQ is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement. Clinically meaningful HAQ response was defined as an improvement of at least 0.22 units from baseline in the HAQ Disability Index.

  Up to 1 year

• Changes in Participant's Fatigue Assessed Using the Mean FACIT-Fatigue Score

  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. 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).

  Up to 1 year

• Change in Fatigue as Measured Using the Fatigue Visual Analog Scale

  The VAS for Fatigue (VAS-F) consists of a 100 mm line, with 0 (No Fatigue) on one end, and 100 (Extreme Fatigue) on the other end, which a participant marks to indicate how much fatigue he or she feels. The marked point in mm is converted into a numeric value from 0 to 100, where 0=no fatigue and 100=maximum fatigue. Increasing numbers=increasing fatigue.

  Up to 1 year

Secondary Outcomes (5)

• Number of Participants With Any Adverse Event and Serious Adverse Event

  Up to 1 year

• Number of Participants With AE or SAE Related Discontinuation of Tocilizumab

  Up to 1 year

• Number of Participants Who Achieved ACR20, ACR50, ACR70 and ACR90 Response

  Up to 1 year

• Number of Participants With C-Reactive Protein Abnormality

  Up to 1 year

• Number of Participants With Erythrocyte Sedimentation Rate Abnormality

  Up to 1 year

Study Arms (1)

Single Arm

EXPERIMENTAL

Drug: tocilizumab [RoActemra/Actemra]

Interventions

tocilizumab [RoActemra/Actemra] DRUG

8 mg/kg (max. 800 mg) iv every 4 weeks, 6 infusions

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients, \>/= 18 years of age
• Active moderate to severe rheumatoid arthritis of \>/= 6 months duration
• \>/=1 non-biologic DMARD and/or anti-TNF therapy at stable dose for \>/=8 weeks at any time prior to study treatment
• Inadequate clinical response to non-biologic DMARD or anti-TNF therapy
• Oral corticosteroids must be at stable dose for at least 25 out of 28 days prior to first dose of study drug

You may not qualify if:

• Pregnant or lactating women
• Major surgery (including joint surgery) within 8 weeks prior to screening or major surgery planned within 6 months of enrolment
• Rheumatic autoimmune disease other than RA
• Functional class IV (ACR classification)
• Prior history of or current joint disease other than RA
• Intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
• Previous treatment with RoActemra/Actemra
• Known active current or history of recurrent infection
• History of or currently active primary or secondary immunodeficiency
• Active tuberculosis requiring treatment within the previous 3 years
• Positive for HIV

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (4)

King Fahad Specialist Hospital; Oncology

Dammam, 31444, Saudi Arabia

Location

King Abdulaziz University Hospital

Jeddah, 21589, Saudi Arabia

Location

Heraa General Hospital; Rheumatology

Mecca, Saudi Arabia

Location

King Fahad Medical City; Gastroentrology

Riyadh, 11525, Saudi Arabia

Location

Related Publications (1)

• Abdulkader OAF, Qushmaq K, Aljishi F. Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor. Ann Saudi Med. 2016 May-Jun;36(3):190-6. doi: 10.5144/0256-4947.2016.190.

  PMID: 27236390 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Roche Trial Information Hotline
• Organization: F. Hoffmann-La Roche AG

global.trial_information@roche.com

+41 616878333

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 31, 2011
• Study Start: November 30, 2011
• Primary Completion: May 12, 2013
• Study Completion: May 12, 2013
• Last Updated: August 16, 2017
• Results First Posted: March 28, 2016

Record last verified: 2017-07

Locations

SA (4)