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| Name | Class |
|---|---|
| Eisai Co., Ltd. | INDUSTRY |
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This study will be conducted in Japan, South Korea and Taiwan to evaluate the optimal dosage of methotrexate (MTX) as an add-on therapy to adalimumab (ADA) in participants with rheumatoid arthritis (RA) who have not achieved remission by MTX monotherapy.
The erythrocyte MTX-polyglutamates (MTX-PG) concentration will be measured to evaluate its relationship to the efficacy and safety of MTX therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MTX-Monotherapy Group | Experimental | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48. |
|
| ADA/MTX-Maximum Tolerated Dose Group | Experimental | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48. |
|
| ADA/MTX-Reduced Dose Group | Experimental | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methotrexate | Drug | Route of Administration: Oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS | SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. | Week 48 |
| Measure | Description | Time Frame |
|---|---|---|
| Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS | SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Yuko Kaneko, MD, PhD | Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fujita Health University Hospital | Aichi | Japan | ||||
| Chiba University Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39874232 | Derived | Tamai H, Ikeda K, Miyamoto T, Taguchi H, Kuo CF, Shin K, Hirata S, Okano Y, Sato S, Yasuoka H, Kuwana M, Ishii T, Kameda H, Kojima T, Nishi Y, Mori M, Miyagishi H, Toshima G, Sato Y, Tsai WC, Takeuchi T, Kaneko Y; MIRACLE Study Group. Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial. Ann Rheum Dis. 2025 Jan;84(1):41-48. doi: 10.1136/ard-2024-226350. Epub 2025 Jan 2. | |
| 38251524 |
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| ID | Title | Description |
|---|---|---|
| FG000 | MTX-Monotherapy Before Week 24 Randomization | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. Methotrexate: Route of Administration: Oral |
| FG001 |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Before Week 24 Randomization |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 15, 2019 | Apr 10, 2023 |
Not provided
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|
| Adalimumab | Drug | Route of Administration: Subcutaneous |
|
|
| Week 48 |
| American College of Rheumatology (ACR) 20 Response Rate at Week 48 | ACR 20 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 20 response will be referred to as ACR 20 response rate.
| Week 48 |
| American College of Rheumatology (ACR) 50 Response Rate at Week 48 | ACR 50 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 50 response will be referred to as ACR 50 response rate.
| Week 48 |
| American College of Rheumatology (ACR) 70 Response Rate at Week 48 | ACR 70 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 70 response will be referred to as ACR 70 response rate.
| Week 48 |
| Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48 | HAQ-DI is a patient-reported questionnaire, consists of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week as: without any difficulty (0); with some difficulty (1); with much difficulty (2); unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0=no disability and 3=very severe, high-dependency disability. Normal physical function is defined by HAQ-DI score of < 0.5. | Week 48 |
| Change in Modified Total Sharp Score ≤ 0.5 at Week 48 | Bone erosions will be evaluated for each region from a scale of 0 (no damage) to 5 (complete collapse of the joint). The score will be 0 to 5 for each hand joint, and 0 to 10 for each foot joint. The maximum total erosion score of both hands will be 160 points, and that of both feet will be 120 points. Joint space narrowing will be evaluated for each region from a scale of 0 (no damage) to 4 (ankylosis or luxation). The maximum total joint space narrowing score of both hands will be 120 points, and that of both feet will be 48 points. Erosion scores and joint space narrowing scores were added to obtain the mTSS (range from 0 to 448). | Week 48 |
| Chiba |
| Japan |
| Hiroshima University Hospital | Hiroshima | Japan |
| Kawasaki Municipal Hospital | Kanagawa | Japan |
| Tokai University Hospital | Kanagawa | Japan |
| Tohoku University Hospital | Miyagi | Japan |
| Nagoya University Hospital | Nagoya | Japan |
| Seirei Hamamatsu General Hospital | Shizuoka | Japan |
| Keio University Hospital | Tokyo | Japan |
| National Hospital Organization Tokyo Medical Center | Tokyo | Japan |
| Nippon Medical School Hospital | Tokyo | Japan |
| Toho University Ohashi Medical Center | Tokyo | Japan |
| Chungbuk National University Hospital | Cheongju-si | South Korea |
| Chungnam National University Hospital | Daejeon | South Korea |
| Gachon University Gil Medical Center | Incheon | South Korea |
| Seoul National University Bundang Hospital | Seongnam | South Korea |
| Seoul Metropolitan Government Seoul National University Boramae Medical Center | Seoul | South Korea |
| The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | South Korea |
| Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital | Kaohsiung City | Taiwan |
| Kaohsiung Medical University Chung-Ho Memorial Hospital | Kaohsiung City | Taiwan |
| China Medical University Hospital | Taichung | Taiwan |
| National Cheng Kung University Hospital | Tainan | Taiwan |
| National Taiwan University Hospital | Taipei | Taiwan |
| Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital | Taoyuan | Taiwan |
| Derived |
| Tamai H, Ikeda K, Miyamoto T, Taguchi H, Kuo CF, Shin K, Hirata S, Okano Y, Sato S, Yasuoka H, Kuwana M, Ishii T, Kameda H, Kojima T, Taninaga T, Mori M, Miyagishi H, Sato Y, Tsai WC, Takeuchi T, Kaneko Y; MIRACLE study collaborators. Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): a randomised, open-label, non-inferiority trial. Lancet Rheumatol. 2023 Apr;5(4):e215-e224. doi: 10.1016/S2665-9913(23)00070-X. |
| MTX-Monotherapy Group After Week 24 |
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48. Methotrexate: Route of Administration: Oral |
| FG002 | ADA/MTX-Maximum Tolerated Dose Group After Week 24 | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
| FG003 | ADA/MTX-Reduced Dose Group After Week 24 | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
| COMPLETED | FAS at week 24 |
|
| NOT COMPLETED |
|
|
| After Week 24 Randomization |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Full-analysis Set | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. Methotrexate: Route of Administration: Oral |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||||
| Duration from the Diagnosis of Rheumatoid Arthritis | Mean | Standard Deviation | days |
| |||||||||||||||||
| Bodyweight | Mean | Standard Deviation | kg |
| |||||||||||||||||
| Estimated Glomerular Filtration Rate (eGFR) | Mean | Standard Deviation | mL/min/1.73m² |
| |||||||||||||||||
| Current or Past Smoker | Count of Participants | Participants |
| ||||||||||||||||||
| Simplified Disease Activity Index (SDAI) | SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL, 0- with no maximum limit). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.3 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. | Mean | Standard Deviation | scores on a scale |
| ||||||||||||||||
| 28-Joint Disease Activity Score of Erythrocyte Sedimentation Rate (DAS28-ESR) | DAS28-ESR is a validated combined index of rheumatoid arthritis disease activity calculated as 0.56*√(Tender Joint Count, 0-28) + 0.28*√(Swollen Joint Count, 0-28) + 0.7*ln(Erythrocyte Sedimentation Rate, mm/hr) + 0.014*(Patient's global assessment, 0-100 mm on visual analogue scale). Scores on the DAS28-ESR range from 0 to 10, where higher scores represent higher disease activity. DAS28-ESR < 2.6 indicates disease remission, ≥ 2.6 to 3.2 = low disease activity, > 3.2 to 5.1 = moderate disease activity, and > 5.1 = high disease activity. | Mean | Standard Deviation | scores on a scale |
| ||||||||||||||||
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | HAQ-DI is a patient-reported questionnaire, consists of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week as: without any difficulty (0); with some difficulty (1); with much difficulty (2); unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0=no disability and 3=very severe, high-dependency disability. Normal physical function is defined by HAQ-DI score of < 0.5. | Mean | Standard Deviation | scores on a scale |
| ||||||||||||||||
| Rheumatoid Factor Positive | One person was not tested. | Count of Participants | Participants |
| |||||||||||||||||
| Anti-cyclic Citrullinated Peptide Antibody Positive | Two people were not tested. | Count of Participants | Participants |
| |||||||||||||||||
| Comorbidities | Count of Participants | 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 | Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in mFAS | SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. | In the modified Full Analysis Set based on non-responder imputation. The modified Full Analysis Set was defined as those with evaluable data set at one or more timepoints after randomization including 66 of 68 subjects in ADA/MTX-Maximum Tolerated Dose Group and 61 of 66 subjects in ADA/MTX-Reduced Dose Group. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Simple Disease Activity Index (SDAI) Remission Rate at Week 48 in PPS | SDAI is a validated combined index of rheumatoid arthritis disease activity, defined as the sum of Swollen Joint Count (0-28), Tender Joint Count (0-28), Patient's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), Physician's Global Assessment of Disease Activity (measured on a visual analogue scale with a range of 0 [none] to 10 [most severe]), and C-reactive protein (mg/dL). Higher scores represent higher disease activity. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity. | In the Per Protocol Set based on non-responder imputation. The Per Protocol Set is defined as a group of subjects among modified Full Analysis Set who adequately complied with the protocol including 58 of 66 subjects in ADA/MTX-Maximum Tolerated Dose Group and 61 of 61 subjects in ADA/MTX-Reduced Dose Group. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | American College of Rheumatology (ACR) 20 Response Rate at Week 48 | ACR 20 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 20 response will be referred to as ACR 20 response rate.
| In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | American College of Rheumatology (ACR) 50 Response Rate at Week 48 | ACR 50 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 50 response will be referred to as ACR 50 response rate.
| In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | American College of Rheumatology (ACR) 70 Response Rate at Week 48 | ACR 70 response is defined as a subject meeting all of the following 3 criteria based on the evaluation results of tender joint count, swollen joint count, VAS (physician- and patient reported), HAQ, and CRP. Also, the proportion of ACR 70 response will be referred to as ACR 70 response rate.
| In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Health Assessment Questionnaire - Disability Index ≤0.5 at Week 48 | HAQ-DI is a patient-reported questionnaire, consists of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week as: without any difficulty (0); with some difficulty (1); with much difficulty (2); unable to do (3). Scores on each task were summed and averaged to provide an overall score from 0 to 3, where 0=no disability and 3=very severe, high-dependency disability. Normal physical function is defined by HAQ-DI score of < 0.5. | In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change in Modified Total Sharp Score ≤ 0.5 at Week 48 | Bone erosions will be evaluated for each region from a scale of 0 (no damage) to 5 (complete collapse of the joint). The score will be 0 to 5 for each hand joint, and 0 to 10 for each foot joint. The maximum total erosion score of both hands will be 160 points, and that of both feet will be 120 points. Joint space narrowing will be evaluated for each region from a scale of 0 (no damage) to 4 (ankylosis or luxation). The maximum total joint space narrowing score of both hands will be 120 points, and that of both feet will be 48 points. Erosion scores and joint space narrowing scores were added to obtain the mTSS (range from 0 to 448). | In the Full Analysis Set based on non-responder imputation. Primary and secondary analysis were performed in subjects randomized at week 24 and planed to receive ADA, not including MTX-Monotherapy Group. | Posted | Count of Participants | Participants | Week 48 |
|
48 weeks
All adverse events were followed up for 70 days from the final dose of study drug or until recovery, whichever comes first.
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 | All From Week 0 to Week 48 | Participants in Safety Analysis Set | 0 | 291 | 23 | 291 | 122 | 291 |
| EG001 | MTX-Monotherapy Before Week 24 Randomization | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. Methotrexate: Route of Administration: Oral | 0 | 291 | 9 | 291 | 94 | 291 |
| EG002 | MTX-Monotherapy Group After Week 24 | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the maximum tolerated dose (MTD) of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and simple disease activity index (SDAI) remission is achieved at Week 24, the MTX therapy will continue until Week 48. Methotrexate: Route of Administration: Oral | 0 | 105 | 6 | 105 | 25 | 105 |
| EG003 | ADA/MTX-Maximum Tolerated Dose Group After Week 24 | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to the MTX therapy until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous | 0 | 68 | 5 | 68 | 14 | 68 |
| EG004 | ADA/MTX-Reduced Dose Group After Week 24 | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous | 0 | 66 | 3 | 66 | 6 | 66 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ankle fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Bronchiectasis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Cardiac failure acute | Cardiac disorders | Systematic Assessment |
| ||
| Cholecystitis acute | Hepatobiliary disorders | Systematic Assessment |
| ||
| Cholecystitis chronic | Hepatobiliary disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Gastric ulcer haemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastroenteritis | Infections and infestations | Systematic Assessment |
| ||
| Humerus fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Inguinal hernia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Lymphoproliferative disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Multiple fractures | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Pleurisy | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumocystis jirovecii pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Pyelonephritis | Infections and infestations | Systematic Assessment |
| ||
| Radius fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Spondylolisthesis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Thyroid cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Wrist fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Liver function test abnormal | Investigations | Systematic Assessment |
| ||
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Nasopharyngitis | Infections and infestations | Systematic Assessment |
| ||
| Upper respiratory tract infection | Infections and infestations | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Abdominal pain upper | Gastrointestinal disorders | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Herpes zoster | Infections and infestations | Systematic Assessment |
| ||
| Influenza | Infections and infestations | Systematic Assessment |
| ||
| Stomatitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
| ||
| Epigastric discomfort | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastroesophageal reflux disease | Gastrointestinal disorders | Systematic Assessment |
| ||
| Mouth ulceration | Gastrointestinal disorders | Systematic Assessment |
| ||
| Pharyngitis | Infections and infestations | Systematic Assessment |
| ||
| Transaminases increased | Investigations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Urticaria | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Y Kaneko | Keio University School of Medicine | +81-3-5363-3786 | ykaneko@z6.keio.jp |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 27, 2021 | Apr 10, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D001327 | Autoimmune Diseases |
| D003240 | Connective Tissue Diseases |
| D012216 | Rheumatic Diseases |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D008727 | Methotrexate |
| D000068879 | Adalimumab |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Lack of Efficacy |
|
| Adverse Event |
|
| Lost to Follow-up |
|
| Protocol Violation |
|
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Taiwan |
|
|
| OG001 | ADA/MTX-Reduced Dose Group | Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
|
| ADA/MTX-Reduced Dose Group |
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
|
| ADA/MTX-Reduced Dose Group |
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
|
| ADA/MTX-Reduced Dose Group |
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
|
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48.
Methotrexate: Route of Administration: Oral
Adalimumab: Route of Administration: Subcutaneous
|
|
Participants will receive Methotrexate (MTX) at a starting dose of 6 to 8 mg/week, which will be promptly escalated to the MTD of ≤25 mg/week up to Week 12, and maintained until Week 24. If the dosage of MTX is maintained ≥ 10 mg/week and SDAI remission is not achieved at Week 24, Adalimumab (ADA) 40 mg will be administered subcutaneously every other week in addition to low-dose MTX (6 to 8 mg/week) treatment until Week 48. Methotrexate: Route of Administration: Oral Adalimumab: Route of Administration: Subcutaneous |
|
|