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

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.

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: tocilizumab [RoActemra/Actemra]

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• Finland
  • Hyvinkää, Finland, 05800
    • Kiljavan Lääketutkimus Oy
  • Hämeenlinna, Finland, 13530
    • Kanta-Hämeen Keskussairaala ; Reumatologia
  • Riihimäki, Finland, 11101
    • Kanta-Hämeen keskussairaala; Riihimäen aluesairaala Reumapoliklinikka

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: tocilizumab [RoActemra/Actemra]; 8mg/kg iv every 4 weeks for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)	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.	Baseline up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Activity Score (DAS28)	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.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving DAS28 Remission (DAS28 <2.6)	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.	Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants Achieving American College of Rheumatology (ACR) 20% (ACR20), ACR50 and ACR70 Response	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).	Weeks 4, 8, 12, 16, 20, and 24
C-Reactive Protein (CRP) Level		Baseline, Weeks 4, 8, 12, 16, 20, and 24
Erythrocyte Sedimentation Rate (ESR)	The erythrocyte sedimentation rate (ESR) is the rate at which red blood cells sediment in a period of one hour.	Baseline, Weeks 4, 8, 12, 16, 20, and 24
Percentage of Participants Who Discontinued the Study		Up to Week 24
Percentage of Participants With Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) Level Elevation More Than 1.5 Times Upper Limit of Normal	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.	Up to Week 24
Percentage of Participants With Lipid Level Elevations	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)'.	Week 24
Neutrophil Count		Baseline, Weeks 4, 8, and 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2008
• Primary Completion (Actual): May 26, 2010
• Study Completion (Actual): May 26, 2010

Study Registration Dates

• First Submitted: December 16, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Actual): August 3, 2017
• Last Update Submitted That Met QC Criteria: June 28, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: ML22012; 2008-004126-16