Clinical Trials List
Protocol NumberM13-545
NCT Number(ClinicalTrials.gov Identfier)NCT02706873
Completed
2016-04-01 - 2020-11-30
Phase III
Terminated3
ICD-10M06.9
Rheumatoid arthritis, unspecified
A Phase 3, Randomized, Double-Blind Study Comparing ABT-494 Once Daily Monotherapy to Methotrexate (MTX) Monotherapy in MTX-Naïve Subjects with Moderately to Severely Active Rheumatoid Arthritis
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Po-Hao Huang 風濕免疫科
- 黃建中 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃光永 Division of Rheumatology
- CHENG-HAN WU Division of Rheumatology
- 許寶寶 Division of Rheumatology
- 童建學 Division of Rheumatology
- 呂明錡 Division of Rheumatology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- CHENG-HAN WU 風濕免疫科
- PING-NING HSU 風濕免疫科
- 郭佑民 風濕免疫科
- CHIEH-YU SHEN 風濕免疫科
- KO-JEN LI 風濕免疫科
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Moderately to Severely Active Rheumatoid Arthritis
Objectives
The objectives of Period 1 were the following:
To compare the safety and efficacy of upadacitinib 7.5 mg once daily (QD) monotherapy (for participants in Japan only), 15 mg QD monotherapy, and 30 mg QD monotherapy versus weekly methotrexate monotherapy for the treatment of signs and symptoms of RA in methotrexate-naïve adults with moderately to severely active RA;
To compare the efficacy of upadacitinib 15 mg QD monotherapy and upadacitinib 30 mg QD monotherapy versus weekly methotrexate monotherapy for prevention of structural progression in methotrexate-naïve adults with moderately to severely active RA.
The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.
Test Drug
ABT-494
Active Ingredient
ABT-494
Dosage Form
Extended-Release Tablet
Dosage
15 mg, 30 mg
Endpoints
Primary Outcome Measures :
1. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis [ Time Frame: Baseline and Week 12 ]
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
a. ≥ 50% improvement in 68-tender joint count;
b. ≥ 50% improvement in 66-swollen joint count; and
c. ≥ 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
2. Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis [ Time Frame: Week 24 ]
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 24.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
3. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis [ Time Frame: Baseline and Week 12 ]
The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
a. ≥ 20% improvement in 68-tender joint count;
b. ≥ 20% improvement in 66-swollen joint count; and
c. ≥ 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
4. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis [ Time Frame: Baseline to Week 24 ]
The 2nd primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24.
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.
1. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis [ Time Frame: Baseline and Week 12 ]
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
a. ≥ 50% improvement in 68-tender joint count;
b. ≥ 50% improvement in 66-swollen joint count; and
c. ≥ 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
2. Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis [ Time Frame: Week 24 ]
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 24.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
3. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis [ Time Frame: Baseline and Week 12 ]
The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
a. ≥ 20% improvement in 68-tender joint count;
b. ≥ 20% improvement in 66-swollen joint count; and
c. ≥ 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
4. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis [ Time Frame: Baseline to Week 24 ]
The 2nd primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24.
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion was assessed in 16 joints in each hand/wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A change from Baseline greater than 0 indicates progression.
Inclution Criteria
Main Inclusion:
1. Adult male or female, at least 18 years old.
2. Diagnosis of RA for ≥ 3 months who also fulfill the 2010 ACR/EULAR classification criteria for
RA.
3. Naïve to MTX or, if already on MTX, have received no more than 3 weekly MTX doses with
requirement to complete a 4-week MTX washout before the first dose of study drug.
4. Subjects with prior exposure to csDMARDs other than MTX may be enrolled if completed the
washout period as specified below or should be at least five times the mean terminal elimination
half-life of a drug:
≥ 4 weeks prior to first dose of study drug for minocycline, penicillamine, sulfasalazine,
hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide,
tacrolimus, cyclosporine, mycophenolate;
≥ 8 weeks prior to first dose of study drug for leflunomide if no elimination procedure was
followed, or adheres to an elimination procedure (i.e., 11 days with colestyramine, or 30 days
washout with activated charcoal or as per local label).
5. Subject meets both of the following disease activity criteria:
a. ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at
Screening and Baseline Visits; and
b. hsCRP ≥ 5 mg/L (central lab, ULN 2.87 mg/L) at Screening Visit.
6. ≥ 1 bone erosion on x-ray (by local reading) OR in the absence of a documented bone erosion, both
positive rheumatoid factor and positive anti-cyclic citrullinated peptide autoantibodies are required at
Screening.
1. Adult male or female, at least 18 years old.
2. Diagnosis of RA for ≥ 3 months who also fulfill the 2010 ACR/EULAR classification criteria for
RA.
3. Naïve to MTX or, if already on MTX, have received no more than 3 weekly MTX doses with
requirement to complete a 4-week MTX washout before the first dose of study drug.
4. Subjects with prior exposure to csDMARDs other than MTX may be enrolled if completed the
washout period as specified below or should be at least five times the mean terminal elimination
half-life of a drug:
≥ 4 weeks prior to first dose of study drug for minocycline, penicillamine, sulfasalazine,
hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide,
tacrolimus, cyclosporine, mycophenolate;
≥ 8 weeks prior to first dose of study drug for leflunomide if no elimination procedure was
followed, or adheres to an elimination procedure (i.e., 11 days with colestyramine, or 30 days
washout with activated charcoal or as per local label).
5. Subject meets both of the following disease activity criteria:
a. ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at
Screening and Baseline Visits; and
b. hsCRP ≥ 5 mg/L (central lab, ULN 2.87 mg/L) at Screening Visit.
6. ≥ 1 bone erosion on x-ray (by local reading) OR in the absence of a documented bone erosion, both
positive rheumatoid factor and positive anti-cyclic citrullinated peptide autoantibodies are required at
Screening.
Exclusion Criteria
Main Exclusion:
1. Intolerant to MTX.
2. Prior exposure to any JAK inhibitor (including but not limited to tofacitinib, baricitinib, and
filgotinib).
3. Prior exposure to any bDMARD(s).
4. History of inflammatory joint disease other than RA (including but not limited to gout, systemic
lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and
non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma,
polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms], or any arthritis with
onset prior to age 17 years). History of secondary Sjogren's Syndrome is permitted.
5. Laboratory values meeting the following criteria within the Screening period prior to the first dose of
study drug: serum aspartate transaminase > 2 × ULN; serum alanine transaminase > 2 × ULN;
estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease
formula < 40 mL/min/1.73 m2
; total white blood cell count < 2,500/µL; absolute neutrophil count
< 1,500/µL; platelet count < 100,000/µL; absolute lymphocyte count < 850/µL; and hemoglobin
< 10 g/dL.
1. Intolerant to MTX.
2. Prior exposure to any JAK inhibitor (including but not limited to tofacitinib, baricitinib, and
filgotinib).
3. Prior exposure to any bDMARD(s).
4. History of inflammatory joint disease other than RA (including but not limited to gout, systemic
lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and
non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma,
polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms], or any arthritis with
onset prior to age 17 years). History of secondary Sjogren's Syndrome is permitted.
5. Laboratory values meeting the following criteria within the Screening period prior to the first dose of
study drug: serum aspartate transaminase > 2 × ULN; serum alanine transaminase > 2 × ULN;
estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease
formula < 40 mL/min/1.73 m2
; total white blood cell count < 2,500/µL; absolute neutrophil count
< 1,500/µL; platelet count < 100,000/µL; absolute lymphocyte count < 850/µL; and hemoglobin
< 10 g/dL.
The Estimated Number of Participants
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Taiwan
12 participants
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Global
975 participants
