Not provided
Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| JapicCTI-050146 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TA-650 3 mg/kg | Experimental |
| |
| TA-650 6 mg/kg | Experimental |
| |
| TA-650 10 mg/kg | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TA-650 3 mg/kg | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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]) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19626391 | Background | 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. | |
| 28865493 | Derived |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | TA-650 3 mg/kg | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. |
| FG001 | TA-650 6 mg/kg | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. |
| FG002 | TA-650 10 mg/kg | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| FG003 | Open-label | 327 patients received TA-650 at 3 mg/kg treatment during the open-label period. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Open-label Period |
|
| ||||||||||||||||||
| Double-blind Period |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | TA-650 3 mg/kg | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. |
| BG001 | TA-650 6 mg/kg | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | percent change | baseline and week 54 |
|
54 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | TA-650 3 mg/kg (Double-blind) | 99 patients received TA-650 at 3mg/kg treatment during the double-blind period starting from week14. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pericardial effusion | Cardiac disorders | 10.0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | 10.0 |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trials, Information Desk | Tanabe Pharma Corporation | cti-inq-ml.JP@ml.tanabe-pharma.com |
Not provided
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069285 | Infliximab |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| TA-650 6 mg/kg | Drug | 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 | Drug | 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. |
|
|
| 54 weeks |
| 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 |
| 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 |
| 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 |
| 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 √(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. | baseline and week 54 |
| 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 |
| 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 |
| 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 |
| Pharmacokinetics Positive- ATI | ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay. | 54 weeks |
| Takeuchi T, Miyasaka N, Inui T, Yano T, Yoshinari T, Abe T, Koike T. High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study. Arthritis Res Ther. 2017 Sep 2;19(1):194. doi: 10.1186/s13075-017-1401-2. |
| Withdrawal by Subject |
|
| not come to a hospital |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| BG002 | TA-650 10 mg/kg | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | TA-650 6 mg/kg | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. |
| OG002 | TA-650 10 mg/kg | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. |
|
|
| 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]) | Posted | Number | percentage of participants | 54 weeks |
|
|
|
| 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. | Posted | Mean | Standard Deviation | count | 54 weeks |
|
|
|
| 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. | Posted | Mean | Standard Deviation | count | 54 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | mg/dl | 54 weeks |
|
|
|
| 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 √(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. | Posted | Mean | Standard Deviation | units on a scale | baseline and week 54 |
|
|
|
| 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. | Posted | Mean | Standard Deviation | units on a scale | 54 weeks |
|
|
|
| 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. | Posted | Median | Inter-Quartile Range | score | baseline and week 54 |
|
|
|
| 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. | Not Posted | 54 weeks | Participants |
| Secondary | Pharmacokinetics Positive- ATI | ATI (antibody to Infliximab) was measured by a modification of an enzyme immunoassay. | Posted | Number | participants | 54 weeks |
|
|
|
| 7 |
| 99 |
| 93 |
| 99 |
| EG001 | TA-650 6 mg/kg (Double-blind) | 104 patients received TA-650 at 6mg/kg treatment during the double-blind period starting from week14. | 5 | 104 | 93 | 104 |
| EG002 | TA-650 10 mg/kg (Double-blind) | 104 patients received TA-650 at 10mg/kg treatment during the double-blind period starting from week14. | 9 | 104 | 96 | 104 |
| EG003 | Open-label | 327 patients received TA-650 at 3 mg/kg treatment during the open-label period. | 17 | 327 | 153 | 327 |
| Pericarditis | Cardiac disorders | 10.0 |
|
| Ascites | Gastrointestinal disorders | 10.0 |
|
| Enterocolitis | Gastrointestinal disorders | 10.0 |
|
| Gastric ulcer perforation | Gastrointestinal disorders | 10.0 |
|
| Inguinal hernia | Gastrointestinal disorders | 10.0 |
|
| Mallory-Weiss syndrome | Gastrointestinal disorders | 10.0 |
|
| Pancreatitis acute | Gastrointestinal disorders | 10.0 |
|
| Peritonitis | Gastrointestinal disorders | 10.0 |
|
| Bile duct obstruction | Hepatobiliary disorders | 10.0 |
|
| Cryptococcosis | Infections and infestations | 10.0 |
|
| Gastroenteritis | Infections and infestations | 10.0 |
|
| Osteomyelitis | Infections and infestations | 10.0 |
|
| Pneumonia legionella | Infections and infestations | 10.0 |
|
| Pyelonephritis | Infections and infestations | 10.0 |
|
| Sepsis | Infections and infestations | 10.0 |
|
| Tonsillitis | Infections and infestations | 10.0 |
|
| Pneumonia bacterial | Infections and infestations | 10.0 |
|
| Anastomotic ulcer | Injury, poisoning and procedural complications | 10.0 |
|
| Ulna fracture | Injury, poisoning and procedural complications | 10.0 |
|
| Osteonecrosis | Musculoskeletal and connective tissue disorders | 10.0 |
|
| Bile duct cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10.0 |
|
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10.0 |
|
| Tongue neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10.0 |
|
| Uterine cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10.0 |
|
| Carpal tunnel syndrome | Nervous system disorders | 10.0 |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Cataract | Eye disorders | 10.0 |
|
| Retinal vein occlusion | Eye disorders | 10.0 |
|
| Gait disturbance | General disorders | 10.0 |
|
| Anaphylactoid reaction | Immune system disorders | 10.0 |
|
| Bronchiolitis | Infections and infestations | 10.0 |
|
| Pneumocystis jiroveci pneumonia | Infections and infestations | 10.0 |
|
| Hand fracture | Injury, poisoning and procedural complications | 10.0 |
|
| Joint dislocation | Injury, poisoning and procedural complications | 10.0 |
|
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 10.0 |
|
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 10.0 |
|
| Loss of consciousness | Nervous system disorders | 10.0 |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 10.0 |
|
| Vertigo | Ear and labyrinth disorders | 10.0 |
|
| Conjunctivitis | Eye disorders | 10.0 |
|
| Abdominal pain upper | Gastrointestinal disorders | 10.0 |
|
| Constipation | Gastrointestinal disorders | 10.0 |
|
| Dental caries | Gastrointestinal disorders | 10.0 |
|
| Diarrhoea | Gastrointestinal disorders | 10.0 |
|
| Dyspepsia | Gastrointestinal disorders | 10.0 |
|
| Nausea | Gastrointestinal disorders | 10.0 |
|
| Stomach discomfort | Gastrointestinal disorders | 10.0 |
|
| Stomatitis | Gastrointestinal disorders | 10.0 |
|
| Chest discomfort | General disorders | 10.0 |
|
| Chest pain | General disorders | 10.0 |
|
| Malaise | General disorders | 10.0 |
|
| Pyrexia | General disorders | 10.0 |
|
| Hepatic function abnormal | Hepatobiliary disorders | 10.0 |
|
| Bronchitis | Infections and infestations | 10.0 |
|
| Gastroenteritis | Infections and infestations | 10.0 |
|
| Herpes zoster | Infections and infestations | 10.0 |
|
| Nasopharyngitis | Infections and infestations | 10.0 |
|
| Oral candidiasis | Infections and infestations | 10.0 |
|
| Paronychia | Infections and infestations | 10.0 |
|
| Pharyngitis | Infections and infestations | 10.0 |
|
| Pneumonia | Infections and infestations | 10.0 |
|
| Sinusitis | Infections and infestations | 10.0 |
|
| Tinea infection | Infections and infestations | 10.0 |
|
| Contusion | Injury, poisoning and procedural complications | 10.0 |
|
| Alanine aminotransferase increased | Investigations | 10.0 |
|
| Aspartate aminotransferase increased | Investigations | 10.0 |
|
| Blood pressure increased | Investigations | 10.0 |
|
| Gamma-glutamyltransferase increased | Investigations | 10.0 |
|
| Blood urine present | Investigations | 10.0 |
|
| Heart rate increased | Investigations | 10.0 |
|
| Liver function test abnormal | Investigations | 10.0 |
|
| White blood cell count decreased | Investigations | 10.0 |
|
| White blood cell count increased | Investigations | 10.0 |
|
| Protein urine present | Investigations | 10.0 |
|
| Blood alkaline phosphatase increased | Investigations | 10.0 |
|
| Antinuclear antibody positive | Investigations | 10.0 |
|
| DNA antibody positive | Investigations | 10.0 |
|
| Cell marker increased | Investigations | 10.0 |
|
| Back pain | Musculoskeletal and connective tissue disorders | 10.0 |
|
| Dizziness | Nervous system disorders | 10.0 |
|
| Headache | Nervous system disorders | 10.0 |
|
| Choking sensation | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Upper respiratory tract inflammation | Respiratory, thoracic and mediastinal disorders | 10.0 |
|
| Acne | Skin and subcutaneous tissue disorders | 10.0 |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | 10.0 |
|
| Eczema | Skin and subcutaneous tissue disorders | 10.0 |
|
| Heat rash | Skin and subcutaneous tissue disorders | 10.0 |
|
| Pruritus | Skin and subcutaneous tissue disorders | 10.0 |
|
| Rash | Skin and subcutaneous tissue disorders | 10.0 |
|
| Urticaria | Skin and subcutaneous tissue disorders | 10.0 |
|
Not provided
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
|
| ACR70% improvement (percentage) |
|
|
|
|