A Study Investigating the Efficacy and Safety of ABT-494 Given With Methotrexate (MTX) in Subjects With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone



Status:Completed
Conditions:Arthritis, Rheumatoid Arthritis
Therapuetic Areas:Rheumatology
Healthy:No
Age Range:18 - 100
Updated:6/17/2016
Start Date:March 2014
End Date:June 2015

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A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 With Background Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone

This is a randomized, double-blind, parallel-group, placebo controlled, multicenter study to
assess the safety and efficacy of ABT-494 in subjects with active rheumatoid arthritis who
have failed Methotrexate alone.


Inclusion Criteria:

1. Diagnosed with RA based on either the 1987-revised ACR classification criteria or the
2010 American College of Rheumatology (ACR)/European League against Rheumatism
(EULAR) criteria for ≥ 3 months.

2. 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.

- hsCRP > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and
anti-Cyclic Citrullinated Peptide (CCP) at Screening.

3. 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.

4. 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)

5. 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.

6. 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 PRN are allowed but may not be taken 24 hours prior to any
study visit.

7. 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:

1. Female who is pregnant or breastfeeding.

2. Prior exposure to Janus Activated Kinase (JAK) inhibitor (e.g., tofacitinib,
baricitinib).

3. Prior exposure to any investigational or approved biologic RA therapy.

4. 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.

5. 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).

6. Subject has been treated with intra-articular or parenteral administration of
corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.

7. 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
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