A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of ABT-494 for the Induction of Symptomatic and Endoscopic Remission in Subjects with Moderately to Severely Active Crohn's Disease who have Inadequately Responded to or are Intolerant to Immunomodulators or Anti-TNF Therapy

1. Male or female >= 18 and <= 75 years of age at Baseline.
2. Diagnosis of ileal, colonic, or ileocolonic Crohn's disease for >= 3 months prior to Baseline and confirmed by endoscopy during the Screening Period or endoscopy performed within 15 days of the Screening Visit. Appropriate documentation of biopsy results consistent with the diagnosis of CD, in the assessment of the Investigator, must be available.
3. Average daily liquid/very soft stool frequency score >= 2.5 or average daily abdominal pain score >= 2.0.
4. CDAI >= 220 and <= 450.
5. Simplified Endoscopic Score for Crohn's disease (SES-CD) >= 6 (or >= 4 for subjects with disease limited to the ileum), confirmed by a central reader.
• A video-recorded ileocolonoscopy performed within 15 days prior to Screening can be used for the local and central reader assessment.
6. Subject has inadequately responded to or experienced intolerance to previous treatment with immunomodulators (e.g., azathioprine, 6-mercaptopurine, or methotrexate) and/or an anti-TNF agent (e.g., infliximab, adalimumab, or certolizumab pegol). The clinical measures that defined inadequate response should be based on the physician/investigator clinical assessment.
Note: Criteria for inadequate response to or experienced intolerance to previous treatment with immunomodulator or an anti-TNF agent defined as:
• Signs and symptoms of persistently active disease despite a history induction regimen with one of the following agents:
o At least a consecutive 90-day course of azathioprine, 6-mercaptopurine or injectable MTX prior to Baseline, with a stable dose for at least 28 days prior to Baseline of azathioprine >= 1.5 mg/kg/day or 6-MP >= 1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation or a documented 6-TGN level of at least 230 pmol/8 × 108 RBC or higher on the current dosing regimen) or MTX >= 15 mg/week (subcutaneous [SC]/Intramuscular [IM]), or a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time.
At least one 6-week induction with Infliximab: 5 mg/kg IV, 3 doses at least 2 weeks apart
o At least one 4-week induction with Adalimumab: one 160 mg SC dose (or 80 mg SC dose in approved countries) followed by one 80 mg SC dose (or 40 mg SC dose in approved countries) followed by one 40 mg dose at least 2 weeks apart
o At least one 4-week induction with Certolizumab pegol: 400 mg SC, 2 doses at least 2 weeks apart OR
• Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify) OR
• History of intolerance of at least one TNF antagonist (including, but not limited to infusion related reaction, demyelination, congestive heart failure and infection)
7. 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 anti-TB prophylaxis, prior to Baseline.

colitis.
2. Subject with previous exposure to JAK inhibitor (e.g., tofacitinib, baricitinib).
3. Subjects who discontinued biologic therapy such as Infliximab (REMICADE), Certolizumab pegol (CIMZIA), Adalimumab (HUMIRA), Vedolizumab (ENTYVIO), Natalizumab (TYSABRI) < 8 weeks prior to Baseline. Subjects who discontinued Ustekinumab (Stelara®) less than 12 weeks prior to Baseline.
4. Subject received azathioprine or 6-mercaptopurine (6-MP) within 10 days of Baseline.
5. Subject who previously or currently use oral aminosalicylates or MTX and meets one of the following criteria:
• Has not been on stable doses for at least 14 days prior to Baseline; or
• Has discontinued use of aminosalicylates or MTX within 14 days of Baseline.
6. Subject who previously or currently use oral corticosteroid and meets one of the following criteria:
• Is receiving prednisone or prednisone equivalent > 30 mg/day within 7 days of Baseline;
• Is receiving budesonide > 9 mg/day within 7 days of Baseline;
• Has discontinued use of corticosteroid within 7 days of Baseline;
• Has not been on stable doses of corticosteroid for at least 7 days prior to Baseline; or
• Has been taking both oral budesonide and prednisone (or equivalent) simultaneously.
7. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.
8. Subject on probiotics who has not been on stable dose for at least 14 days prior to Baseline.
9. Subject who previously or currently use Crohn's disease related antibiotics and meets one of the following criteria:
• Has not been on stable doses for at least 14 days prior to Baseline;
• Has discontinued Crohn's disease related antibiotics within 14 days of Baseline.
10. Subject received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline.
11. Subject has received therapeutic enema or suppository, other than required for endoscopy, within 7 days prior to Screening and/or during the Screening Period.
12. Subject who has had surgical bowel resection within the past 6 months or is planning any resection while enrolled in the study.
13. Subject with an ostomy, ileoanal pouch or symptomatic bowel stricture.
14. Subject with an abdominal or peri-anal abscess.
15. Subject who has short bowel syndrome.
16. Subject who previously received stem cell transplantation or Subject who previously received fecal microbial transplantation in the past 1 month.
17. Subject who received non-steroidal anti-inflammatory drugs (NSAIDs) (except topical NSAIDs and the use of low dose aspirin for cardiovascular (CV) protection) within 14 days prior to Screening and during the Screening Visit.
18. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit.
19. Subject currently receiving total parenteral nutrition (TPN) or plan to receive TPN at any time during the course of the study.
20. Subject with positive Clostridium difficile (C. difficile) toxin stool assay during the Screening Period.
21. Screening laboratory and other analyses show any of the following abnormal results:
• Serum Aspartate Transaminase (AST) or Alanine transaminase (ALT) > 21.5 × upper limit of the reference range (ULN);
• Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m2;
• Total White Blood Cell (WBC) count < 3,000/µL;
• Absolute neutrophil count (ANC) < 1,200/µL;
• Platelet count < 100,000/µL;
• Absolute lymphocytes count < 750/µL;
• Hemoglobin < 9 g/dL.
22. Any active or recurrent viral infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study, including recurrent/disseminated herpes zoster or known history of human immunodeficiency virus (HIV).
22. Any active or recurrent viral infection that based on the investigator's clinical assessment makes the subject an unsuitable candidate for the study, including recurrent/disseminated herpes zoster or known history of human immunodeficiency virus (HIV).
23. Hepatitis B (HBs Ag positive [+] or detected sensitivity on the HBV DNA PCR qualitative test for HBc Ab positive subjects) or hepatitis C (HCV RNA detectable in any subject with anti-HCV Ab).
24. Subject with any active or chronic recurring infections or untreated latent TB.
25. History of moderate to severe congestive heart failure (NYHA class III or IV), cerebrovascular accident and any other condition within 6 months, which in the opinion of the Investigator, would put the subject at risk by participation in the study.
26. Use of known strong CYP3A inhibitors (e.g., clarithromycin, conivaptan, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole, grapefruit juice) or strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort) from Screening through the end of the study.
27. Receipt of any live vaccine within 1 month prior to the Screening Visit, or will require live vaccination during study participation including up to 1 month after the last dose of study drug.
28. Evidence of current colonic dysplasia, history of high grade colonic dysplasia, or history of malignancy (including of the gastrointestinal tract) other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
29. Has had any uncontrolled and/or clinically significant (per Investigator's judgment) illness or has had any surgical procedure within 30 days prior to Screening.
30. Positive pregnancy test at Screening (serum) or Baseline (urine).
31. Female subjects who are breastfeeding or considering becoming pregnant during the study.
32. Subject is considered by the Investigator, for any reason, to be an unsuitable candidate for the study.
33. Subject who received any investigational agent or procedure within 30 days or 5 half-lives prior to Baseline, whichever is longer.
34. History of clinically significant drug or alcohol abuse in the last 12 months.