A Study Investigating the Efficacy and Safety of Upadacit... | NCT02066389

NCT02066389

ID	Type	Description	Link
2013-003984-72	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Participants received placebo capsules twice daily for 12 weeks.	Drug: Placebo
Upadacitinib 3 mg BID	Experimental	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib
Upadacitinib 6 mg BID	Experimental	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib
Upadacitinib 12 mg BID	Experimental	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib
Upadacitinib 18 mg BID	Experimental	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib
Upadacitinib 24 mg QD	Experimental	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Tablets for oral administration	Placebo
Upadacitinib

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 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).	Baseline and Week 12

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 50% improvement in 68-tender joint count; ≥ 50% improvement in 66-swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician's global assessment of disease activity Patient's global assessment of disease activity Patient's assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High sensitivity C-reactive protein (hsCRP).

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria for ≥ 3 months.
Have active RA as defined by the following minimum disease activity criteria:
- ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
- ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
- high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.
Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.
Except for MTX, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:
- ≥ 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide
- ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)
Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.
Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken as needed are allowed but may not be taken 24 hours prior to any study visit.
Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit.

Exclusion Criteria:

Female who is pregnant or breastfeeding.
Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).
Prior exposure to any investigational or approved biologic RA therapy.
Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit.
Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).
Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.
Screening laboratory values meeting the following criteria:
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN
- Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m²
- Total white blood cell count (WBC) < 3,000/µL
- Absolute neutrophil count (ANC) < 1,200/µL
- Platelet count < 100,000/µL
- Absolute lymphocytes count < 750/ µL
- Hemoglobin < 9 gm/dL

Name	Affiliation	Role
AbbVie Inc.	AbbVie	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
C.V. Mehta MD, Med Corporation /ID# 126380		Hemet	California	92543	United States
Omega Research Consultants, LLC /ID# 125780

PubMed Identifier	Type	Citation	Retractions
27390150	Background	Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S. Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016 Dec;68(12):2857-2866. doi: 10.1002/art.39808.
34041702

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
FG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:

≥ 20% improvement in 68-tender joint count;
≥ 20% improvement in 66-swollen joint count; and
≥ 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).

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Posted

Number

percentage of participants

Baseline and Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.
OG003	Upadacitinib 12 mg BID	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.
OG004	Upadacitinib 18 mg BID	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.
OG005	Upadacitinib 24 mg QD	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.

Units	Counts
Participants	OG00046 OG00148 OG00249 OG003

Title

Denominators

Categories

Title	Measurements
	OG00050.0 OG00164.6 OG00273.5 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Chi-squared		0.153	Statistical tests were 1-sided at a significance level of 0.05.													Superiority
OG000 OG002		Chi-squared		0.018

Secondary

Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

A participant was a responder if the following 3 criteria for improvement from baseline were met:

≥ 50% improvement in 68-tender joint count;
≥ 50% improvement in 66-swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
- Physician's global assessment of disease activity
- Patient's global assessment of disease activity
- Patient's assessment of pain
- Health Assessment Questionnaire - Disability Index (HAQ-DI)
- High sensitivity C-reactive protein (hsCRP).

Posted

Number

percentage of participants

Baseline and Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Secondary

Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

A participant was a responder if the following 3 criteria for improvement from baseline were met:

≥ 70% improvement in tender joint count;
≥ 70% improvement in swollen joint count; and
≥ 70% 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).

Posted

Number

percentage of participants

Baseline and Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Secondary

Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12

The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale (VAS) from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity.

LDA is defined as a DAS28(CRP) score < 3.2.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Secondary

Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12

The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to 10 where higher scores indicate more disease activity.

CR is defined as a DAS28(CRP) score < 2.6.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Secondary

Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12

The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

LDA is defined as a CDAI score ≤ 10.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Secondary

Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12

CR is defined as a CDAI score ≤ 2.8.

Posted

Number

percentage of participants

Week 12

ID	Title	Description
OG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
OG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
OG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.	50	0	50	2	50
EG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	50	0	50	5	50
EG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	50	2	50	7	50
EG003	Upadacitinib 12 mg BID	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	50	1	50	17	50
EG004	Upadacitinib 18 mg BID	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	50	3	50	6	50
EG005	Upadacitinib 24 mg QD	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.	49	2	49	6	49

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
PYREXIA	General disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG0030 events0 affected50 at risk EG0041 events1 affected50 at risk EG0050 events0 affected49 at risk
PNEUMONIA	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
FOREARM FRACTURE	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
HEAD INJURY	Injury, poisoning and procedural complications	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
OSTEONECROSIS	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0021 events1 affected50 at risk EG003
LUNG NEOPLASM MALIGNANT	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0021 events1 affected50 at risk EG003
SCIATICA	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
SYNCOPE	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
OVARIAN CYST	Reproductive system and breast disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
LEUKOPENIA	Blood and lymphatic system disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG0033 events3 affected50 at risk EG0041 events1 affected50 at risk EG0050 events0 affected49 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0021 events1 affected50 at risk EG003
INFLUENZA	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
NASOPHARYNGITIS	Infections and infestations	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected50 at risk EG0011 events1 affected50 at risk EG0022 events2 affected50 at risk EG003
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0010 events0 affected50 at risk EG0020 events0 affected50 at risk EG003
DYSLIPIDAEMIA	Metabolism and nutrition disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0011 events1 affected50 at risk EG0020 events0 affected50 at risk EG003
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0011 events1 affected50 at risk EG0023 events3 affected50 at risk EG003
HEADACHE	Nervous system disorders	MedDRA 17.1	Systematic Assessment	EG0001 events1 affected50 at risk EG0012 events2 affected50 at risk EG0021 events1 affected50 at risk EG003
COUGH	Respiratory, thoracic and mediastinal disorders	MedDRA 17.1	Systematic Assessment	EG0000 events0 affected50 at risk EG0011 events1 affected50 at risk EG0021 events1 affected50 at risk EG003

ID	Term
D001172	Arthritis, Rheumatoid
D009140	Musculoskeletal Diseases
D001168	Arthritis
D007592	Joint Diseases

ID	Term
D012216	Rheumatic Diseases
D003240	Connective Tissue Diseases
D017437	Skin and Connective Tissue Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Title	Description
BG000	Placebo	Participants received placebo capsules twice daily for 12 weeks.
BG001	Upadacitinib 3 mg BID	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.
BG002	Upadacitinib 6 mg BID	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.
BG003	Upadacitinib 12 mg BID	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.
BG004	Upadacitinib 18 mg BID	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.
BG005	Upadacitinib 24 mg QD	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
BG006	Total	Total of all reporting groups