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A Study of Tocilizumab in Patients With Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic DMARDs

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00810277
First received: December 16, 2008
Last updated: March 1, 2016
Last verified: March 2016
  Purpose
This single arm study will assess the safety and efficacy of tocilizumab in patients with moderate to severe active rheumatoid arthritis who have an inadequate response to current non-biologic DMARDs. Patients will receive iv infusions of tocilizumab 8mg/kg every 4 weeks for a total of 6 infusions, either as monotherapy or in combination with their current non-biologic DMARDs.

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Study to Evaluate the Safety and 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 DMARDs.

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 Adverse Events (SAEs) [ Time Frame: Baseline up to Week 24 ] [ Designated as safety issue: No ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious as well as non-serious AEs.


Secondary Outcome Measures:
  • Disease Activity Score (DAS28) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from swollen joint count (SJC) and tender joint count (TJC) using 28 joints count, erythrocyte sedimentation rate (ESR) (mm/hour) or C-reactive protein (CRP) (mg/dL), and general health (GH) status (measured on a 0 to 100 mm Visual Analogue Scale [VAS] where 0=no disease activity and 100=worst disease activity). DAS28 was calculated using following formulas: DAS28-ESR = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*GH of disease activity; DAS28-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(10*CRP+1) + 0.014*GH of disease activity. DAS28-ESR was adopted to calculate DAS28 if effective ESR data was available; otherwise DAS28-CRP was adopted to calculate DAS28. Total score range: 0-10, higher score=more disease activity. DAS28 <=3.2 implied low disease activity, DAS >3.2 to 5.1 implied moderate disease activity and DAS >5.1 implied high disease activity, and DAS28 <2.6 = clinical remission.

  • Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6) [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from SJC and TJC using 28 joints count, ESR (mm/hour) or CRP (mg/dL), and general health (GH) status (measured on a 0 to 100 mm Visual Analogue Scale [VAS] where 0=no disease activity and 100=worst disease activity). DAS28 was calculated using following formulas: DAS28-ESR = 0.56*square root (sqrt) (TJC28) + 0.28*sqrt(SJC28) + 0.70*natural logarithm (ln) (ESR) + 0.014*GH of disease activity; DAS28-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(10*CRP+1) + 0.014*GH of disease activity. DAS28-ESR was adopted to calculate DAS28 if effective ESR data was available; otherwise DAS28-CRP was adopted to calculate DAS28. Total score range: 0-10, higher score=more disease activity. DAS28 <=3.2 implied low disease activity, DAS >3.2 to 5.1 implied moderate disease activity and DAS >5.1 implied high disease activity, and DAS28 <2.6 = clinical remission.

  • Percentage of Participants Achieving American College of Rheumatology (ACR) 20% (ACR20), ACR50 and ACR70 Response [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    ACR20, ACR50, and ACR70 response: greater than or equal to (>=) 20 percent (%), 50%, and 70% improvement respectively, in tender or swollen joint counts and in 3 of the following criteria: (1) Participant's assessment of pain (measured on a 0 to 100 mm VAS where 0=no pain and 100=unbearable pain); (2) Participant's assessment of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity); (3) Investigator's global assessment of disease activity (measured on a 0 to 100 mm VAS where 0=no disease activity and 100=worst disease activity); (4) Participant's assessment of functional disability via health assessment questionnaire (HAQ) (measured using 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do).

  • C-Reactive Protein (CRP) Level [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
  • Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells sediment in a period of one hour.

  • Percentage of Participants Who Discontinued the Study [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Level Elevation More Than 1.5 Times Upper Limit of Normal [ Time Frame: Up to Week 24 ] [ Designated as safety issue: No ]
    Normal range of ALT is 7 to 56 units per liter (U/L) of serum. Normal range of AST is 5 to 40 units per liter (U/L) of serum.

  • Percentage of Participants With Lipid Level Elevations [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Low density lipoprotein (LDL) level was categorized as 'Optimal (less than [<] 100 milligram per deciliter [mg/dL])', 'Near Optimal/Above Optimal (100-129 mg/dL)', 'Borderline High (130-159 mg/dL)', 'High (160-189 mg/dL)', and 'Very high (190 mg/dL)'. High density lipoprotein (HDL) level was categorized as 'Acceptable (40-59 mg/dL)', 'High (>=60 mg/dL)'. Total cholesterol (TC) level was categorized as 'Desirable (<200 mg/dL)', 'Borderline High (200-239 mg/dL)', 'High (>=240 mg/dL)'.

  • Neutrophil Count [ Time Frame: Baseline, Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]

Enrollment: 14
Study Start Date: November 2008
Study Completion Date: May 2010
Primary Completion Date: May 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

  Eligibility

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

Inclusion Criteria:

  • adult patients, >=18 years of age;
  • moderate to severe rheumatoid arthritis;
  • inadequate response to current non-biologic DMARDs

Exclusion Criteria:

  • rheumatic autoimmune disease or inflammatory joint disease other than rheumatoid arthritis;
  • previous treatment with other biologics.
  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: NCT00810277

Locations
Finland
Helsinki, Finland, 00130
Hyvinkää, Finland, 05800
Hämeenlinna, Finland, 13530
Riihimäki, Finland, 11101
Tampere, Finland, 33100
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00810277     History of Changes
Other Study ID Numbers: ML22012  2008-004126-16 
Study First Received: December 16, 2008
Results First Received: March 1, 2016
Last Updated: March 1, 2016
Health Authority: Finland: Finnish Medicines Agency

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

ClinicalTrials.gov processed this record on December 07, 2016