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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-002358-57 | EudraCT Number |
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The primary objective is to compare the safety and efficacy of multiple doses of ABT-494 versus placebo in moderately to severely active RA subjects on stable background MTX therapy with inadequate response or intolerance to anti-TNF biologic therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo BID | Placebo Comparator | Placebo twice daily (BID) for 12 weeks. |
|
| ABT-494 3 mg BID | Experimental | ABT-494 3 mg twice daily (BID) for 12 weeks. |
|
| ABT-494 6 mg BID | Experimental | ABT-494 6 mg twice daily (BID) for 12 weeks. |
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| ABT-494 12 mg BID | Experimental | ABT-494 12 mg twice daily (BID) for 12 weeks. |
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| ABT-494 18 mg BID | Experimental | ABT-494 18 mg twice daily (BID) for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-494 | Drug | ABT-494 capsule administered orally twice daily (BID). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hs CRP). Last observation carried forward (LOCF) was used for missing data. | Baseline (Week 0) and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12 | Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used. | Baseline (Week 0) and Week 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| AbbVie Inc | AbbVie | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27389975 | Background | Kremer JM, Emery P, Camp HS, Friedman A, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S, Keystone EC. A Phase IIb Study of ABT-494, a Selective JAK-1 Inhibitor, in Patients With Rheumatoid Arthritis and an Inadequate Response to Anti-Tumor Necrosis Factor Therapy. Arthritis Rheumatol. 2016 Dec;68(12):2867-2877. doi: 10.1002/art.39801. | |
| 34041702 |
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The study included a screening period of 30 days.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo BID | Placebo twice daily (BID) for 12 weeks. |
| FG001 | ABT-494 3 mg BID | ABT-494 3 mg twice daily (BID) for 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | Placebo for ABT-494 capsule administered orally twice daily (BID). |
|
| Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 | Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used. | Baseline (Week 0) and Week 12 |
| Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12 | LDA is defined as DAS28 from 2.6 to < 3.2 at Week 12. CR is defined as DAS28 (CRP) < 2.6 at Week 12. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used. | Baseline (Week 0) and Week 12 |
| Number of Subjects Achieving CR Based on DAS28 at Week 12 | The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used. | Baseline (Week 0) and Week 12 |
| Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27. |
| 31610021 | Derived | Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30. |
| 31194885 | Derived | Mohamed MF, Klunder B, Camp HS, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy in Phase II Trials in Rheumatoid Arthritis and Basis for Phase III Dose Selection. Clin Pharmacol Ther. 2019 Dec;106(6):1319-1327. doi: 10.1002/cpt.1543. Epub 2019 Aug 23. |
| 29076110 | Derived | Klunder B, Mohamed MF, Othman AA. Population Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects with Rheumatoid Arthritis: Analyses of Phase I and II Clinical Trials. Clin Pharmacokinet. 2018 Aug;57(8):977-988. doi: 10.1007/s40262-017-0605-6. |
| FG002 | ABT-494 6 mg BID | ABT-494 6 mg twice daily (BID) for 12 weeks. |
| FG003 | ABT-494 12 mg BID | ABT-494 12 mg twice daily (BID) for 12 weeks. |
| FG004 | ABT-494 18 mg BID | ABT-494 18 mg twice daily (BID) for 12 weeks. |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo BID | Placebo twice daily (BID) for 12 weeks. |
| BG001 | ABT-494 3 mg BID | ABT-494 3 mg twice daily (BID) for 12 weeks. |
| BG002 | ABT-494 6 mg BID | ABT-494 6 mg twice daily (BID) for 12 weeks. |
| BG003 | ABT-494 12 mg BID | ABT-494 12 mg twice daily (BID) for 12 weeks. |
| BG004 | ABT-494 18 mg BID | ABT-494 18 mg twice daily (BID) for 12 weeks. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| 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 | No |
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| 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 | Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12 | Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hs CRP). Last observation carried forward (LOCF) was used for missing data. | Subjects in the modified intent-to-treat (mITT) population with a baseline value and at least 1 post-baseline value | Posted | Count of Participants | Participants | No | Baseline (Week 0) and Week 12 |
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| Secondary | Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12 | Response defined as at least 50% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used. | Subjects in the mITT population with a baseline value and at least 1 post-baseline value. | Posted | Count of Participants | Participants | No | Baseline (Week 0) and Week 12 |
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| Secondary | Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12 | Response defined as at least 70% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, PtGA; PGA, HAQ-DI, and hs CRP. LOCF was used. | Subjects in the mITT population with a baseline value and at least 1 post-baseline value. | Posted | Count of Participants | Participants | No | Baseline (Week 0) and Week 12 |
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| Secondary | Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12 | LDA is defined as DAS28 from 2.6 to < 3.2 at Week 12. CR is defined as DAS28 (CRP) < 2.6 at Week 12. The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used. | Subjects in the mITT population with a baseline value and at least 1 post-baseline value. | Posted | Count of Participants | Participants | No | Baseline (Week 0) and Week 12 |
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| Secondary | Number of Subjects Achieving CR Based on DAS28 at Week 12 | The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, hs CRP, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission. LOCF was used. | Subjects in the mITT population with a baseline value and at least 1 post-baseline value. | Posted | Count of Participants | Participants | No | Baseline (Week 0) and Week 12 |
|
Treatment-emergent AEs (TEAEs) were collected from first dose of study drug until up to 30 days after discontinuation of study drug (up to 16 weeks); SAEs were collected from the time informed consent was obtained (20 weeks).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo BID | Placebo twice daily (BID) for 12 weeks. | 0 | 56 | 1 | 56 | 9 | 56 |
| EG001 | ABT-494 3 mg BID | ABT-494 3 mg twice daily (BID) for 12 weeks. | 0 | 55 | 2 | 55 | 13 | 55 |
| EG002 | ABT-494 6 mg BID | ABT-494 6 mg twice daily (BID) for 12 weeks. | 0 | 55 | 2 | 55 | 9 | 55 |
| EG003 | ABT-494 12 mg BID | ABT-494 12 mg twice daily (BID) for 12 weeks. | 0 | 55 | 0 | 55 | 14 | 55 |
| EG004 | ABT-494 18 mg BID | ABT-494 18 mg twice daily (BID) for 12 weeks. | 0 | 55 | 1 | 55 | 27 | 55 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| PANCREATITIS | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| TRANSIENT ISCHAEMIC ATTACK | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| BENIGN PROSTATIC HYPERPLASIA | Reproductive system and breast disorders | MedDRA (17.1) | Systematic Assessment |
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| ACUTE RESPIRATORY FAILURE | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
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| BRONCHIECTASIS | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
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| PULMONARY EMBOLISM | Respiratory, thoracic and mediastinal disorders | MedDRA (17.1) | Systematic Assessment |
| |
| DEEP VEIN THROMBOSIS | Vascular disorders | MedDRA (17.1) | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| LEUKOPENIA | Blood and lymphatic system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| CONSTIPATION | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA (17.1) | Systematic Assessment |
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| PYREXIA | General disorders | MedDRA (17.1) | Systematic Assessment |
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| GASTROENTERITIS | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| SINUSITIS | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| URINARY TRACT INFECTION | Infections and infestations | MedDRA (17.1) | Systematic Assessment |
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| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA (17.1) | Systematic Assessment |
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| HYPERLIPIDAEMIA | Metabolism and nutrition disorders | MedDRA (17.1) | Systematic Assessment |
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| ARTHRALGIA | Musculoskeletal and connective tissue disorders | MedDRA (17.1) | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA (17.1) | Systematic Assessment |
| |
| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA (17.1) | Systematic Assessment |
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AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Services | AbbVie | 800-633-9110 |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| D007592 | Joint Diseases |
| D001168 | Arthritis |
| D009140 | Musculoskeletal Diseases |
| ID | Term |
|---|---|
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000613732 | upadacitinib |
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| Male |
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| Other |
| Chi-squared | < 0.001 | Other |
| Chi-squared | < 0.001 | Other |
| ABT-494 18 mg BID |
ABT-494 18 mg twice daily (BID) for 12 weeks. |
|
|
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| ABT-494 18 mg BID |
ABT-494 18 mg twice daily (BID) for 12 weeks. |
|
|
|
| ABT-494 12 mg BID |
ABT-494 12 mg twice daily (BID) for 12 weeks. |
| OG004 | ABT-494 18 mg BID | ABT-494 18 mg twice daily (BID) for 12 weeks. |
|
|
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| OG004 | ABT-494 18 mg BID | ABT-494 18 mg twice daily (BID) for 12 weeks. |
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