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

Purpose

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.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: TA-650 3 mg/kg Drug: TA-650 6 mg/kg Drug: TA-650 10 mg/kg	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Clinical Study to Assess the Efficacy and Safety of Increased Dose of TA-650(Infliximab) in Patients With Rheumatoid Arthritis

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis

Drug Information available for: Infliximab

U.S. FDA Resources

Further study details as provided by Mitsubishi Tanabe Pharma Corporation:

Primary Outcome Measures:

Numeric Index of American College of Rheumatology Response (ACR-N, N Shows the Percent Improvement) [ Time Frame: baseline and week 54 ] [ Designated as safety issue: No ]
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.

Secondary Outcome Measures:

Percentage of Participants Achieving American College of Rheumatology 20, 50 and 70% Response (ACR20, 50, 70) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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])
Tender Joint Counts (TJC) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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.
Swollen Joint Count (SJC) [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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.
CRP Level [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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.
Change From Baseline in DAS28 [ Time Frame: baseline and week 54 ] [ Designated as safety issue: No ]
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 √(TJC) + 0.28 x √(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.
Change From Baseline to Week 54 in HAQ [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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.
Change in Modified Total Sharp Score (mTSS) at week54 From Baseline [ Time Frame: baseline and week 54 ] [ Designated as safety issue: No ]
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.
Pharmacokinetics- Serum Concentration of Infliximab [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
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.
Pharmacokinetics Positive- ATI [ Time Frame: 54 weeks ] [ Designated as safety issue: No ]
ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay.

Enrollment:	327
Study Start Date:	September 2005
Study Completion Date:	May 2007
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: TA-650 3 mg/kg	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. Other Names: Infliximab REMICADE
Experimental: TA-650 6 mg/kg	Drug: 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. Other Names: Infliximab REMICADE
Experimental: TA-650 10 mg/kg	Drug: 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. Other Names: Infliximab REMICADE

Eligibility

Ages Eligible for Study:	20 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	General Manager, Clinical Research Department III, Mitsubishi Tanabe Pharma Corporation
ClinicalTrials.gov Identifier:	NCT00691028 History of Changes
Other Study ID Numbers:	TA-650-13, JapicCTI-050146
Study First Received:	June 3, 2008
Results First Received:	January 29, 2013
Last Updated:	May 19, 2013
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Mitsubishi Tanabe Pharma Corporation:

Rheumatoid Arthritis
RA
Infliximab
TA-650
Remicade

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

Infliximab
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Gastrointestinal Agents
Antirheumatic Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 23, 2013