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Study to Evaluate the Safety, Tolerability and Efficacy of Tocilizumab in Participants With Rheumatoid Arthritis (RA) Who Have an Inadequate Response to Non-Biologic Disease Modifying Anti-rheumatic Drugs (DMARDs) and/or Anti-tumor Necrosis Factor (Anti-TNF) Therapy

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01362062
First Posted: May 27, 2011
Last Update Posted: August 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This observational study will evaluate the safety, tolerability and efficacy of tocilizumab in participants with moderate to severe RA who have an inadequate response to current non-biologic DMARD and/or anti-TNF therapy. Data will be collected from each participant during tocilizumab therapy and on follow-up for a total of 12 months.

Condition Intervention
Rheumatoid Arthritis Drug: Tocilizumab

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Study to Observe the Safety, Tolerability and Efficacy of Tocilizumab in Patients With Moderate to Severe Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-biologic DMARD and/or Anti TNF Therapy.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: Up to 12 months ]
    An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal product. An AE is considered as an SAE if it fulfills one of the following criteria: a) fatal or life-threatening, b) requires in-patient hospitalization or prolongation of existing hospitalization, c) results in a persistent or significant disability, d) results in a congenital abnormality/birth defect, e) is medically significant. AEs included serious as well as non-serious AEs.


Secondary Outcome Measures:
  • Percentage of Participants Achieving a Clinically Meaningful Improvement in Disease Activity Score 28 (DAS28) (Reduction of At Least 1.2 Units) at Every Visit [ Time Frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    DAS28 was calculated from the tender joint count (TJC) of 28 joints, swollen joint count (SJC) of 28 joints, erythrocyte sedimentation rate (ESR) (in millimeters [mm]/hour), and the participant's global assessment of disease activity (100 mm visual analog scale [VAS]: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*square root (√) of TJC + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement.

  • Time Required to Achieve Clinically Meaningful Improvement in DAS28 (Reduction of At Least 1.2 Units) [ Time Frame: Up to 12 months ]
    DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*√(TJC) + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. A reduction of at least 1.2 units of DAS28 score from previous visit is considered as clinically meaningful improvement. Time taken to achieve clinically meaningful improvement in DAS28 was reported.

  • Percentage of Participants Achieving Low Disease Activity (DAS28 Less Than [<] 3.2 Units) at Every Visit [ Time Frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*√(TJC) + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low Disease Activity is defined as DAS28 value of <3.2 Units at the time of assessment.

  • Time Required to Achieve Low Disease Activity (DAS28 <3.2 Units) [ Time Frame: Up to 12 months ]
    DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*√(TJC) + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). The DAS28 scale ranges from 0 to 10, where higher scores represent higher disease activity. Low disease activity is defined as decrease in DAS28 to a value <3.2 Units at the time of assessment. Time taken to achieve low disease activity was reported.

  • Percentage of Participants Achieving Remission (DAS28 <2.6 Units) at Every Visit [ Time Frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*√(TJC) + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). Remission is defined as DAS28 value of <2.6 units at the time of assessment.

  • Time Taken to Achieve Remission (DAS28 <2.6 Units) [ Time Frame: Up to 12 months ]
    DAS28 was calculated from the TJC of 28 joints, SJC of 28 joints, ESR (in mm/hour), and the participant's global assessment of disease activity (100 mm VAS: 0 mm=no disease activity to 100 mm=maximum disease activity). The formula for calculating DAS28 score using ESR value is: 0.56*√(TJC) + 0.28*√(SJC) + 0.70*log natural (ESR) + 0.014*global assessment of disease activity (100 mm VAS). Remission is defined as DAS28 value of <2.6 units at the time of assessment. Time taken to achieve remission is reported.

  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50, ACR70 and ACR90 Responses at Every Visit [ Time Frame: Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 42), Visit 13 (Week 44) ]
    ACR20/ACR50/ACR70/ACR 90 response: greater than or equal to (≥) 20%/50%/70%/90% improvement in tender and swollen joint counts and 20%/50%/70%/90% improvement in 3 of the following 5 criteria: 1) Physician's global assessment of disease activity, 2) Participant assessment of disease activity, 3) Participant assessment of pain (VAS), 4) participant assessment of functional disability via a Health Assessment Questionnaire (HAQ), and 5) ESR at each visit.

  • Change From Baseline (CFB) in ESR Values at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
  • Change From Baseline in C-Reactive Protein (CRP) Levels at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
  • Participant's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    The participant's global assessment of disease activity is assessed on a 0 to 100 mm horizontal 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, and is described as "maximum disease activity" (maximum arthritis disease activity). A negative change from baseline indicated improvement.

  • Physician's Global Assessment of Disease Activity Using VAS: Mean Change From Baseline at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    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, and is described as "maximum disease activity" (maximum arthritis disease activity).

  • Participant's Assessment of Pain Using VAS: Mean Change From Baseline at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    The participant assessed their pain on a 0 to 100 mm horizontal 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, and is described as "unbearable pain". A negative change indicated improvement.

  • Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Every Visit [ Time Frame: Visit 2 (Baseline), Visit 3 (Week 4), Visit 4 (Week 8), Visit 5 (Week 12), Visit 6 (Week 16), Visit 7 (Week 20), Visit 8 (Week 24), Visit 9 (Week 28), Visit 10 (Week 32), Visit 11 (Week 36), Visit 12 (Week 40), Visit 13 (Week 44) ]
    HAQ-DI is a self-completed patient questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and 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. The HAQ-DI is the sum of the scores from all domains and ranged from 0 (best) to 24 (worst). A negative change from baseline indicated improvement.


Enrollment: 110
Actual Study Start Date: October 26, 2010
Study Completion Date: January 1, 2015
Primary Completion Date: January 1, 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
RA Cohort
Participants with active RA who had an inadequate clinical response to current non-biologic disease modifying anti-rheumatoid drug (DMARD) and/or anti-tumor necrosis factor (anti-TNF) therapy being treated with tocilizumab according to the routine clinical practice and in line with prescribing information will be observed for a total duration of 12 months.
Drug: Tocilizumab
Other Name: Actemra

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Rheumatoid arthritis patients with inadequate response to DMARD and/or anti-TNF therapy
Criteria

Inclusion Criteria:

  • Moderate to severe active RA with an inadequate response to existing therapies (DMARDs and/or anti-TNFs)
  • Considered eligible for tocilizumab therapy by the treating physician as per routine clinical practice

Exclusion Criteria:

  • Pregnant or breastfeeding females
  • Immunization with live/attenuated vaccine within 4 weeks prior to baseline
  • Participants with clinically significant raised liver enzyme, abnormal lipid profile, platelet count, hemoglobin, white blood cell and neutrophil count
  • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies
  • Participants with active tuberculosis (TB). Participants with latent TB should be treated with standard anti-mycobacterial therapy before initiating tocilizumab and have a negative chest x ray for active TB at enrolment
  • History of diverticulitis, chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis or other symptomatic lower GI conditions that might predispose to perforations then the benefit risk ratio should be considered by treating physician
  • Know active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infection
  • History of or currently active primary or secondary immunodeficiency or known human immunodeficiency virus (HIV) positive status
  • Any other condition which puts the participant to undue risk for tocilizumab therapy as per local prescribing information or Investigator's judgement
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01362062


Locations
India
Sir Gangaram Hospital
New Delhi, Delhi, India, 110060
Healing Touch City Clinic
Chandigarh, India, 160015
Excel Center
Guwahati, India, 781007
Arthritis Superspeciality Centre
Hubli, India, 580020
Centre for Rheumatic Diseases - Mumbai
Mumbai, India, 400007
Jivdaya Clinic
Mumbai, India, 400086
Fortis Hospital
Noida, India, 201 301
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01362062     History of Changes
Other Study ID Numbers: ML22835
First Submitted: May 26, 2011
First Posted: May 27, 2011
Results First Submitted: March 3, 2016
Results First Posted: April 4, 2016
Last Update Posted: August 2, 2017
Last Verified: June 2017

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