Study To Evaluate The Efficacy And Safety Of Oral PF-06651600 And PF-06700841 In Subjects With Moderate To Severe Crohn's Disease

Inclusion Criteria:

1. Male and/or female subjects 18 years to 75 years of age

2. Documented diagnosis of ileal, ileocolonic, or colonic CD with a minimum diseaseduration of 3 months, as determined by endoscopic and histopathology assessment.

3. Endoscopic confirmation of active disease with total SES CD total score of at least

4. For isolated ileal disease, SES CD total score should be at least 4.

5. An average daily liquid/soft stool frequency (SF) greater than or equal to 2.5 ordaily abdominal pain (AP) greater than or equal to 2.0.

6. Must have inadequate response to, loss of response to, or intolerance to at leastone conventional therapy for CD:

•Steroids; Immunosuppressants (azathioprine [AZA], 6 MP, or methotrexate [MTX]);Anti TNF inhibitors (infliximab, adalimumab,certolizumab); Anti integrin inhibitors (eg, vedolizumab); Anti IL 12/23 inhibitor (ustekinumab).

6. Subjects currently receiving the following treatment for CD are eligible providingthey have been on stable doses as described below:

• Oral corticosteroids (prednisone or equivalent up to 25 mg/day; budesonide upto 9 mg/day). Stable dose for at least 2 weeks prior to baseline. If oralcorticosteroids have been recently discontinued, they must have been stopped atleast 2 weeks prior to baseline. Decreases in steroid use due to AEs areallowed.

• Oral 5 ASA or sulfasalazine are allowed providing that the dose is stable forat least 4 weeks prior to baseline.

• Crohn's disease related antibiotics are allowed providing that the dose isstable for at least 4 weeks prior to baseline. If antibiotics are stopped priorto baseline, they must be discontinued at least 4 days prior to baseline.

Exclusion Criteria:

1. Diagnosis of indeterminate colitis, microscopic colitis, ischemic colitis,infectious colitis, radiation colitis, diverticular disease, ulcerative colitis (UC), or clinical findings suggestive of UC.

2. Presence of active (draining) fistulae or intra abdominal or perineal abscesses.

3. Strictures with obstructive symptoms.

4. Short bowel syndrome.

5. History of bowel perforation requiring surgical intervention within the past 12months.

6. Previous bowel surgery resulting in an existing stoma. Subjects who have a j pouchare excluded, as a j pouch can result in a stoma.

7. History of bowel surgery within 6 months prior to baseline.

8. Subjects displaying clinical signs of fulminant colitis or toxic megacolon.

9. Subjects with primary sclerosing cholangitis.

10. Subjects with evidence of colonic adenomas, dysplasia or neoplasia.

11. Abnormal findings on the chest x ray film such as presence of tuberculosis (TB),general infections, heart failure, or malignancy.

12. Any history of either untreated or inadequately treated latent or active TBinfection, current treatment for active or latent TB infection or evidence ofcurrently active TB by chest x ray, residing with or frequent close contact withindividual(s) with active TB.

13. Subjects receiving the following therapies within the time period described below orexpected to receive any of these therapies during the study period:

14. >9 mg/day of oral budesonide or >25 mg/day of prednisone or equivalent oralsystemic corticosteroid dose within 2 weeks prior to baseline.

15. IV, IM (parenteral), or topical (rectal) treatment of 5 ASA or corticosteroidenemas/suppositories within 2 weeks prior to baseline.

16. Azathioprine, 6 mercaptopurine, or methotrexate within 2 weeks prior tobaseline.

17. Anti TNF inhibitors (or biosimilars thereof) as described below:

• Infliximab within 8 weeks prior to baseline;
• Adalimumab within 8 weeks prior to baseline;
• Certolizumab within 8 weeks prior to baseline;

5. Anti integrin inhibitors (eg, vedolizumab) within 8 weeks prior to baseline.

6. Ustekinumab within 8 weeks prior to baseline.

7. Interferon therapy within 8 weeks prior to baseline.

8. Subjects with prior treatment with lymphocyte depleting agents/therapies within 1 year prior to baseline (eg, CamPath[alemtuzumab], alkylating agents [eg,cyclophosphamide or chlorambucil], total lymphoid irradiation, etc).

9. Subjects who have received rituximab or other selective B lymphocyte depletingagents within 1 year prior to baseline.

10. Subjects previously receiving leukocyte apheresis, including selectivelymphocyte, monocyte, or granulocyte apheresis, or plasma exchange within 6months prior to baseline.

11. Other marketed immunosuppressants or biologics with immunomodulatory propertieswithin 3 months prior to baseline.

12. Subjects who have received other JAK inhibitors within 3 months prior tobaseline.

13. Subjects who have not responded to or have been intolerant of other JAKinhibitors.

14. Other investigational procedures(s) or product(s), such as immunosuppressantsused in transplantation (eg, mycophenolate mofetil, cyclosporine, rapamycin, ortacrolimus) or live (attenuated) vaccine within 30 days prior to baseline.

14. Subjects with history of thrombotic event(s), including deep venousthrombosis (DVT), and known inherited conditions that predispose tohypercoagulability.