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

• ClinicalTrials.gov Identifier: NCT01258712
• Recruitment Status: Completed
• First Posted: December 13, 2010
• Last Update Posted: December 13, 2012
• Sponsor: Chugai Pharma Taiwan
• Information provided by (Responsible Party): Chugai Pharma Taiwan

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Rheumatoid Arthritis (RA)	Drug: Tocilizumab + methotrexate(MTX); Drug: Tocilizumab placebo + methotrexate(MTX)	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 86 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Placebo-controlled Study of Tocilizumab in Combination With Methotrexate for Treatment of Moderate to Severe Rheumatoid Arthritis Patients
• Study Start Date: December 2010
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients with an American College of Rheumatology 20(ACR20) response [ Time Frame: at baseline and week 24 ]

Secondary Outcome Measures :

1. Proportion of patients with ACR50 response [ Time Frame: at baseline and week 24 ]
2. Proportion of patients with ACR70 response [ Time Frame: at baseline and week 24 ]
3. Mean change from baseline of Swollen joint count(SJC) and Tender joint count(TJC) respectively [ Time Frame: at baseline and week 24 ]
4. Mean change from baseline in disease activity using 28-joint modified disease activity score (DAS28) [ Time Frame: at baseline and week 24 ]
5. Proportion of patients achieving DAS28 remission (DAS28 < 2.6) [ Time Frame: at week 24 ]
6. Adverse event incidence [ Time Frame: from baseline to week 24 ]
7. Mean change from baseline to evaluation visits in vital signs [ Time Frame: from baseline to week 24 ]
8. Result of Electrocardiogram. From baseline to evaluation visits [ Time Frame: from baseline to week 24 ]
9. Mean change from baseline visit to evaluation visits in quantitative hematological exam results (including Hb, Ht, RBC, WBC & differential, platelet counts). [ Time Frame: from baseline to week 24 ]
10. 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.). [ Time Frame: from baseline to week 24 ]
11. Mean change from baseline visit to evaluation visits in quantitative serum lipid exam results. [ Time Frame: from baseline to week 24 ]
12. Mean change from baseline visit to evaluation visits in quantitative urinalysis results. [ Time Frame: from baseline to week 24 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Taiwan

Buddhist Dalin Tzu Chi General Hospital

Chiayi, Taiwan

Chang Gung Memorial Hospital -Kaohsiung

Kaohsiung, Taiwan

Kaohsiung Medical University Hospital

Kaohsiung, Taiwan

Kaohsiung Veterans General Hospital

Kaohsiung, Taiwan

Chung Shan Medical University Hospital

Taichung, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan

Cathay General Hospital

Taipei, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Tri-Service General Hospital

Taipei, Taiwan

Chang Gung Memorial Hospital - Linkou

Taoyuan, Taiwan

Sponsors and Collaborators

Chugai Pharma Taiwan

Investigators

• Study Chair: Yoshiaki Someya; Chugai Pharma Taiwan

More Information

• Responsible Party: Chugai Pharma Taiwan
• ClinicalTrials.gov Identifier: NCT01258712
• Other Study ID Numbers: MRA230TW
• First Posted: December 13, 2010
• Last Update Posted: December 13, 2012
• Last Verified: December 2012

Additional relevant MeSH terms:

Arthritis; Arthritis, Rheumatoid; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Methotrexate; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Dermatologic Agents; Enzyme Inhibitors; Folic Acid Antagonists; Immunosuppressive Agents; Immunologic Factors; Antirheumatic Agents; Nucleic Acid Synthesis Inhibitors