Study of Tocilizumab in Combination With Methotrexate for Treatment of Moderate to Severe Rheumatoid Arthritis Patients

Randomized, Placebo-controlled Study of Tocilizumab in Combination With Methotrexate for Treatment of Moderate to Severe Rheumatoid Arthritis Patients

This is a Phase III study to evaluate efficacy and safety of Tocilizumab in patients with Rheumatoid Arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)
• Intervention / Treatment: Drug: Tocilizumab + methotrexate(MTX); Drug: Tocilizumab placebo + methotrexate(MTX)

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 3

Contacts and Locations

Study Locations

• Taiwan
  • Chiayi, Taiwan
    • Buddhist Dalin Tzu Chi General Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Veterans General Hospital
  • Kaohsiung, Taiwan
    • Chang Gung Memorial Hospital -Kaohsiung
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taipei, Taiwan
    • Cathay General Hospital
  • Taoyuan, Taiwan
    • Chang Gung Memorial Hospital - Linkou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with history of moderate-to- severe rheumatoid arthritis for more than 6 months according to the American College of Rheumatology (ACR) 1987 revised criteria for the classification of RA.
• Patients who failed to achieve clinical response to treatment of at least 2 DMARDs(disease modifying anti-rheumatic drug) (including MTX) for at least 12 weeks within 12 months prior to screening, of which MTX must have been at a stable dose of 10-20 mg/wk for at least 12 weeks prior to screening. All other DMARDs should be given at standard therapeutic dose.
• Patients who satisfy swollen joint count (SJC) ≥ 6 (66 joint count) and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.
• C-reactive protein (CRP) level ≥ 1 mg/dl or an erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour at screening and at baseline.

Exclusion Criteria:

• Patients who have received a major surgery including joint surgery 8 weeks prior to the screening or are scheduled to be operated within 6 months after the enrolment.
• Patients with rheumatoid autoimmune disease other than RA, including but not limited to SLE(system lupus erythematosus), or significant systemic involvement secondary to RA.
• Patients who belong to the Class IV of the ACR classification criteria for functional status of RA. (ACR Amended Criteria for the Classification of Functional Capacity in Rheumatoid Arthritis; Class IV: Largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care).
• Patients with a history of hypersensitivity to human, humanized or murine monoclonal antibodies or patients with contraindication for them.
• Patients who currently have or have a history of recurrence of bacterial, viral,fungal, or mycobacterial infections or other infectious diseases; tuberculosis(TB),atypical mycobacterial disease, clinically significant granulomatous disease on chest radiograph, hepatitis B, hepatitis C, or herpes zoster and etc. However, a patient with hand & foot fungal infections can participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: Tocilizumab + methotrexate(MTX); Tocilizumab:8 mg/kg every4weeks,IV infusion methotrexate:10-20 mg/week
Placebo Comparator: 2	Drug: Tocilizumab placebo + methotrexate(MTX); Tocilizumab placebo:8 mg/kg every 4 weeks,IV infusion methotrexate:10-20 mg/week

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with an American College of Rheumatology 20(ACR20) response	at baseline and week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean change from baseline of Swollen joint count(SJC) and Tender joint count(TJC) respectively	at baseline and week 24
Mean change from baseline in disease activity using 28-joint modified disease activity score (DAS28)	at baseline and week 24
Proportion of patients achieving DAS28 remission (DAS28 < 2.6)	at week 24
Adverse event incidence	from baseline to week 24
Mean change from baseline to evaluation visits in vital signs	from baseline to week 24
Mean change from baseline visit to evaluation visits in quantitative serum lipid exam results.	from baseline to week 24
Mean change from baseline visit to evaluation visits in quantitative urinalysis results.	from baseline to week 24
Proportion of patients with ACR50 response	at baseline and week 24
Proportion of patients with ACR70 response	at baseline and week 24
Result of Electrocardiogram. From baseline to evaluation visits	from baseline to week 24
Mean change from baseline visit to evaluation visits in quantitative hematological exam results (including Hb, Ht, RBC, WBC & differential, platelet counts).	from baseline to week 24
Mean change from baseline visit to evaluation visits in quantitative Biochemical exam of blood results (including AST, ALT, Alk-p, γ-GTP, LDH, total protein, albumin, total bilirubin, BUN, uric acid, creatinine, glucose, ferritin, K, Na, Cl, Ca, P.).	from baseline to week 24

Collaborators and Investigators

• Sponsor: Chugai Pharma Taiwan
• Investigators: Study Chair: Yoshiaki Someya, Chugai Pharma Taiwan

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: December 8, 2010
• First Submitted That Met QC Criteria: December 10, 2010
• First Posted (Estimate): December 13, 2010

Study Record Updates

• Last Update Posted (Estimate): December 13, 2012
• Last Update Submitted That Met QC Criteria: December 12, 2012
• Last Verified: December 1, 2012

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate
• Other Study ID Numbers: MRA230TW