Efficacy and Safety of Increased Dose of TA-650(Infliximab) in Patients With Rheumatoid Arthritis

Rheumatoid Arthritis Clinical Trial

Official title:

Clinical Study to Assess the Efficacy and Safety of Increased Dose of TA-650(Infliximab) in Patients With Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00691028
• Other study ID #: TA-650-13
• Secondary ID: JapicCTI-050146
• Status: Completed
• Phase: Phase 3
• First received: June 3, 2008
• Last updated: January 30, 2014
• Start date: September 2005
• Est. completion date: May 2007

Study information

• Verified date: January 2014
• Source: Mitsubishi Tanabe Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy, safety and pharmacokinetics of maintenance treatment with 3mg/kg, 6mg/kg or 10mg/kg of TA-650 in combination with methotrexate (MTX) after three infusions (weeks-0, 2, 6) of 3mg/kg in Rheumatoid Arthritis (RA) showing an insufficient response to MTX.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 327
• Est. completion date: May 2007
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with active RA in spite of stable dose of MTX

Exclusion Criteria:

• Having received infliximab in the past

• Having a history of serious infection which caused hospitalization within 6 months before the registration

• Having an active tuberculosis

• Having a complication or a history of malignancy within 5 years before the registration

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• TA-650 3 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6. Then 3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.
• TA-650 6 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6 weeks. Then 6 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.
• TA-650 10 mg/kg
3 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 0, 2 and 6. Then 10 mg/kg of TA-650 will be intravenously infused over a period of more than 2 hours at weeks 14, 22, 30, 38 and 46.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mitsubishi Tanabe Pharma Corporation

References & Publications (1)

Takeuchi T, Miyasaka N, Inoue K, Abe T, Koike T; RISING study. Impact of trough serum level on radiographic and clinical response to infliximab plus methotrexate in patients with rheumatoid arthritis: results from the RISING study. Mod Rheumatol. 2009;19(5):478-87. doi: 10.1007/s10165-009-0195-8. Epub 2009 Jul 22. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Numeric Index of American College of Rheumatology Response (ACR-N, N Shows the Percent Improvement)	The ACR-N index of improvement is the minimum of the following: (1) the percent decrease from baseline in tender joint counts(TJC) or (2) the percent decrease from baseline in swollen joint counts(SJC) or (3) the median percent decrease from baseline for the following: a. Patient's assessment of pain (visual analog scale (VAS) 0-100, 100 worst pain); b. Patient's global assessment of disease activity (VAS 0-100); c. Physician's global assessment of disease activity (VAS 0-100); d. Physical function as measured by the Health Assessment Questionnaire(HAQ)(0-3); e. C-Reactive Protein(CRP) measurement. Higher numbers (maximum:100) indicate more improvement.	baseline and week 54	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 20, 50 and 70% Response (ACR20, 50, 70)	ACR 20 (50 or 70) response is a decrease of at least 20% (50% or 70%) in both TJC and SJC and in 3 to 5 assessments (patient's assessment of pain [VAS] with 0, no pain to 100, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 100, very poor and 0, no arthritis activity to 100, extremely active, respectively]; [HAQ]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; [CRP])	54 weeks	No
Secondary	Tender Joint Counts (TJC)	The TJC was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The TJC was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1.	54 weeks	No
Secondary	Swollen Joint Count (SJC)	The SJC was determined by examination of 66 joints and identifying when swelling was present. The SJC was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1.	54 weeks	No
Secondary	CRP Level	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation. Normal range of CRP is 0 mg/dL to 0.3 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.	54 weeks	No
Secondary	Change From Baseline in DAS28	DAS28 is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x v(TJC) + 0.28 x v(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Total score range:0 to 9.4, higher score indicated more disease activity. DAS28 =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 to 9.4 implied high disease activity and <2.6 implied remission.	baseline and week 54	No
Secondary	Change From Baseline to Week 54 in HAQ	HAQ: patient's assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.	54 weeks	No
Secondary	Change in Modified Total Sharp Score (mTSS) at week54 From Baseline	The mTSS is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 54 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 and joint space narrowing on a scale of 0 (no damage) to 4. Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 390 [maximal disease]). An increase in mTSS from baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.	baseline and week 54	No
Secondary	Pharmacokinetics- Serum Concentration of Infliximab	Serum level of infliximab was measured by enzyme-linked immunosorbent assay (ELISA), using a monoclonal antibody against infliximab. The lowest level of infliximab that could be reliably detected was 0.1 ug/ml.	54 weeks	No
Secondary	Pharmacokinetics Positive- ATI	ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay.	54 weeks	No