A Study of Tocilizumab in Combination With DMARD Therapy in Patients With Active Rheumatoid Arthritis.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00773461
First received: October 15, 2008
Last updated: June 9, 2016
Last verified: June 2016
  Purpose
This 2 arm study will compare the safety and efficacy, with regard to reduction of signs and symptoms, of tocilizumab versus placebo, both in combination with DMARDs, in patients with active rheumatoid arthritis who currently have an inadequate response to DMARD therapy. Patients will be randomized 2:1 to receive tocilizumab 8mg/kg iv or placebo iv every 4 weeks, in conjunction with stable DMARD therapy. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind Study of Safety and Reduction in Signs and Symptoms During Treatment With Tocilizumab Versus Placebo, in Combination With DMARD Therapy, in Patients With Active Rheumatoid Arthritis and Inadequate Response to Current DMARD Therapy

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With an American College of Rheumatology (ACR)20 Response at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    To achieve an ACR20 response required at least a 20% improvement, compared with baseline, in both (tender joints count)TJC and (swollen joints count) SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, health assessment questionnaire disease index (HAQ-DI) and C-reactive protein (CRP). CRP was used primarily for the calculation of the ACR response; if missing, Erythrocyte Sedimentation Rate (ESR) was substituted. ITT sensitivity analysis was carried out using an alternative imputation method (last observation carried forward [LOCF]).


Secondary Outcome Measures:
  • Percentage of Participants With ACR50 and ACR70 Responses at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    To achieve an ACR50 or ACR 70 response required at least a 50% or 70% improvement, compared with baseline in both TJC and SJC, as well as in 3 out of 5 additional ACR core set variables: physician's global assessment of disease activity, participant's global assessment of disease activity, participant's assessment of pain, HAQ-DI and CRP. CRP was used primarily for the calculation of the ACR response; if missing, ESR was substituted.

  • Number of Participants Who Received Escape Therapy [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
    Participants who did not achieve a 20% improvement from baseline in both SJC and TJC at week 16 could, if requested and deemed necessary by the investigator, receive escape therapy, comprising adjustment of the background DMARD dose and/or treatment with a different traditional DMARD.

  • Change in Tender and Swollen Joint Counts From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]

    68 joints were assessed for tenderness and joints were classified as tender/not tender giving a total possible tender joint count score of 0 to 68.

    66 joints were assessed for swelling and joints were classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.


  • Change in Participant's Global Assessment of Disease Activity From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the participant. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.

  • Change in Physician's Global Assessment of Disease Activity From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal VAS by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).

  • Change in Participant's Global Assessment of Pain From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The participants assessed their pain on a 0 to 100 mm VAS. The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.

  • Change in C-Reactive Protein From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The serum concentration of CRP an acute phase inflammatory marker, is measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.

  • Change in ESR From Baseline to Week 24 [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    The ESR was measured in mm/hour. A reduction in the level is considered an improvement.

  • Percentage of Participants With Low Disease Activity and in Clinical Remission [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, 20 and 24 ] [ Designated as safety issue: No ]
    DAS28 calculated from the number of swollen joints and tender joints using the 28-joint count, ESR 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. DAS28 less than or equal to (≤3.2) = low disease activity, DAS28 greater than (>)3.2 to 5.1 = moderate to high disease activity.

  • Change From Baseline to Week 24 in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score [ Time Frame: Baseline and Week 24 ] [ Designated as safety issue: No ]
    FACIT-F is a 13-item questionnaire. Patients 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 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). A higher score reflects an improvement in health status.

  • Mean Rheumatoid Factor at Baseline and Week 24 [ Time Frame: Baseline and 24 Weeks ] [ Designated as safety issue: No ]
    Rheumatoid factor (RF) is a disease characteristic and more than 85% of the participants studied were positive for the factor. These data are from patients who were RF positive. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL.

  • Change in Hemoglobin From Baseline to Week 24 [ Time Frame: Baseline and 24 Weeks ] [ Designated as safety issue: No ]
    Levels of hemoglobin were determined in grams/liter (g/L)as a measure of anemia in participants

  • Change in Health Assessment Questionnaire - Disease Index (HAQ-DI) From Baseline to Week 24 [ Time Frame: Baseline and 24 Weeks ] [ Designated as safety issue: No ]
    HAQ-DI is a self-completed participant questionnaire specific for RA. 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 3=unable to do. The HAQ-DI 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.

  • Percentage of Participants With ACR20 Response by First Week of Onset [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ACR 20 responses are summarized by first onset as a percentage of the total number of responders at week 24. The number of participants first achieving an ACR20 response at each time point is represented by treatment arm as a proportion of the total number of participants that had an ACR20 response at Week 24 using n as the denominator.

  • Time to First Low Disease Activity [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Time to Low disease activity was calculated as the number of days from the first dose of drug administration to the date of first achievement of DAS28≤3.2.

  • Time to First Remission [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Time to first Remission was calculated as the number of days from the date of first dose of study drug administration to the date of first achievement of DAS<2.6


Enrollment: 209
Study Start Date: October 2008
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg iv every 4 weeks for 24 weeks
Placebo Comparator: 2 Drug: Placebo
iv every 4 weeks for 24 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, 18-70 years of age;
  • rheumatoid arthritis for >= 6 months;
  • receiving permitted DMARDs, at a stable dose, for >= 8 weeks prior to baseline;
  • current inadequate clinical response to DMARDs.

Exclusion Criteria:

  • major surgery, including joint surgery, within 8 weeks before entering study, or planned major surgery within 6 months following randomization;
  • rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
  • unsuccessful treatment with an anti-TNF agent;
  • previous treatment with tocilizumab.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00773461

Locations
China
Beijing, China, 100032
Beijing, China, 100044
Beijing, China, 100853
Guangzhou, China, 510630
Harbin, China, 150001
Jinan, China, 250012
Shanghai, China, 200001
Shanghai, China, 200433
Xi'an, China, 710032
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00773461     History of Changes
Other Study ID Numbers: ML21753 
Study First Received: October 15, 2008
Results First Received: December 29, 2015
Last Updated: June 9, 2016
Health Authority: China: Ministry of Health

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2016