Evaluation of Oral Tofacitinib in Children Aged 2 to 17 Years Old Suffering From Moderate to Severe Ulcerative Colitis

Inclusion Criteria:

• Evidence of a personally signed and dated informed consent document and assentdocument.

• Males and females 2 to less than18 years old and weighing at least 10 kg.

• Having a pathology report that confirms colonic inflammation consistent with UC witha clinical diagnosis of UC for at least 12 weeks prior to baseline, with biopsyreport supporting the diagnosis of UC.

• Participants diagnosed with UC at age less than 6 years old, must have had testingand be negative for monogenic disorders associated with very early onset IBD.

• Moderately to severely active UC as defined (via screening colonoscopy) by a Mayoscore of at least 6, with a rectal bleeding score of at least 1 and an endoscopicsubscore of at least 2.

• Pediatric Ulcerative Colitis Activity Index (PUCAI) score greater or equal to 35 .

• No history of dysplasia or colon cancer.

• No evidence or history of untreated or inadequately treated active or latentinfection with Mycobacterium Tuberculosis.

• For participants outside of the United States or the European Union: have had aninadequate response or been intolerant to at least one prior therapy as listed belowor have a medical contraindication to such therapies:

• Oral or intravenous (IV) corticosteroids;

• Azathioprine or 6-mercaptopurine;

• TNF inhibitors or anti integrin therapy.

• For participants in the United States and the European Union: have had an inadequateresponse or intolerance to TNF inhibitors.

• Stable doses of the following therapies for UC:

• Oral 5 Aminosalicyclic acids (ASA) or sulfasalazine

• Oral corticosteroids equivalent to prednisone at most 1 mg/kg up to a maximumof 20 mg/day or budesonide up to 9 mg/day.

• female participant is eligible if she is not pregnant or breastfeeding, If she is awoman of child bearing potential, she needs to be using a contraceptive method thatis highly effective (with a failure rate of <1% per year).

Exclusion Criteria:

• Diagnosis of indeterminate colitis, isolated proctitis, microscopic colitis,infectious colitis, Crohn's disease, or clinical findings suggestive of Crohn'sdisease.

• History of symptomatic obstructive intestinal strictures or active ostomy, orhistory of colectomy, extensive small bowel resection ( greater than100 centimetres)or short bowel syndrome, or hospitalization for UC related reason(s) within 2 weeksof baseline visit.

• Any factors or clinical characteristics potentially related to the risk of venousthromboembolism that may increase the risk associated with study participation orstudy intervention administration or may interfere with the interpretation of studyresults and, in the judgment of the investigator, would make the participantinappropriate for entry into this study.

• Participants who have previously received tofacitinib or another Janus Kinaseinhibitor.

• Vaccination or exposure to a live or attenuated vaccine within the 6 weeks prior tothe first dose of study drug, or who are expected to be vaccinated or to havehousehold exposure to these vaccines during treatment or during the 6 weeksfollowing discontinuation of study drug.

• Participants having received azathioprine, 6-mercaptopurine, methotrexate,thioguanine, infliximab, adalimumab, golimumab, ustekinumab, interferon,cyclosporine, mycophenolate, tacrolimus, IV or rectally administeredcorticosteroids, natalizumab, vedolizumab, other antiadhesion molecules, orinvestigational drugs during the specified time periods prior to baseline wherebythey may still have pharmacokinetic and/or pharmacodynamic effect in the body of theparticipant.

• Previous treatment by leukocyte apheresis including selective lymphocyte, monocyte,or granulocyte apheresis, or plasma exchange within 6 months prior to baseline.

• Treatment by specified prohibited concomitant medications, including moderate topotent CYP3A inducers or inhibitors in the specified time periods prior to the firstdose of study drug or are expected to receive any of these medications during thestudy period.

• Chronic and frequent use of antimotility agents for control of diarrhea (ie,diphenoxylate hydrochloride with atropine sulfate or loperamide).

• History of bowel surgery, including cholecystectomy within 6 months prior tobaseline, history of appendectomy within 3 months prior to baseline, or significanttrauma or major surgery within 4 weeks of screening visit are excluded.

• Participants with the following laboratory values at screening:

• Hemoglobin level lower than 9.0 g/Dl.

• Absolute white blood cell (WBC) count lower than 3000/mm3.

• Absolute neutrophil count lower than 1200/mm3.

• Absolute lymphocyte count lower than 750/mm3.

• Thrombocytopenia as defined by a platelet count lower than 100,000/mm3.

• Estimated bedside Schwartz Glomerular filtration rate (GFR) lower or equal to 40 mL/min/1.73 m2.

• Total bilirubin, aspartate aminostransferase (AST) or alanine aminotransferase (ALT) more than 1.5 times the upper limit of normal.

• Positive stool examinations for enteric pathogens, pathogenic ova or parasites, orC. difficile toxin at screening.

• Participants infected with human immunodeficiency virus (HIV) or hepatitis B or Cviruses.

• History of more than one episode of HZ, a history of disseminated HZ or disseminatedherpes simplex.

• History or current symptoms of any lymphoproliferative disorder (eg, Epstein BarrVirus (EBV) related lymphoproliferative disorder, lymphoma, leukemia,myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive ofcurrently lymphatic disease).

• Clinically significant infections currently or within 3 months prior to baseline (eg, those requiring hospitalization or parenteral antimicrobial therapy oropportunistic infections), a history of any infection requiring antimicrobialtherapy within 2 weeks of baseline, or a history of any infection otherwise judgedby the investigator to have the potential for exacerbation by participation in thestudy.

• Any malignancies or with a history of malignancies, with the exception of adequatelytreated or excised nonmetastatic basal cell or squamous cell cancer of the skin.

• Investigator site staff members directly involved in the conduct of the study andtheir family members, site staff members otherwise supervised by the investigator,or participants who are employees of the Sponsor, including their family members,directly involved in the conduct of the study.

• Participation in other studies involving investigational drug(s) within 2 monthsprior to study entry and/or during study participation.

• Other acute or chronic medical or psychiatric condition including recent (within thepast year) or active suicidal ideation or behavior or laboratory abnormality thatmay increase the risk associated with study participation or study interventionadministration or may interfere with the interpretation of study results and, in thejudgment of the investigator, would make the participant inappropriate for entryinto this study.

• Pregnant female participants; breastfeeding female participants; fertile femaleparticipants of childbearing potential who are unwilling or unable to use a highlyeffective method of contraception as outlined in this protocol for the duration ofthe study and through the telephone follow up visit.

• History of allergies, intolerance or hypersensitivity to lactose or tofacitinib, orany other excipients of the investigational medicinal products, including placebos.