Safety and Efficacy of Efavaleukin Alfa in Participants With Moderately to Severely Active Ulcerative Colitis

Key Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study specificactivities or procedures.

• Men and women aged ≥ 18 to < 80 years at screening visit (≥ 19 to < 80 in SouthKorea).

• Diagnosis of UC established ≥ 3 months prior to enrollment by clinical andendoscopic evidence and corroborated by a histopathology report. If a histopathologyreport is not available at screening, then additional biopsies may be taken duringthe screening period for local histopathology analysis to corroborate.

• Moderately to severely active UC as defined by a modified Mayo score of 5 to 9, witha centrally read endoscopy subscore ≥ 2.

• Has documentation of:

• A surveillance colonoscopy (performed according to local standard) within 12months of day 1 visit for participants with pancolitis of > 8 years duration,or participants with left-sided colitis of > 12 years duration, or participantswith primary sclerosing cholangitis.

• At the discretion of the investigator, a colonoscopy (instead of arectosigmoidoscopy) may be performed as the screening endoscopy for this study.

• For all other participants, up-to-date colorectal cancer surveillance (performed according to local standard). Participants who do not have acolonoscopy report available in source documentation will have a colonoscopyinstead of rectosigmoidoscopy performed as the screening endoscopy for thestudy.

• Participants must have demonstrated inadequate response, loss of response, orintolerance to at least 1 conventional therapy, biologic therapy, or targeted smallmolecule therapy (ie, Janus kinase [JAK]-inhibitor or or S1P modulators), asfollows:

1. Conventional therapy failed participants:

• Corticosteroids (corticosteroid-refractory colitis, defined as signsand/or symptoms of active UC despite oral prednisone [or equivalent] atdoses of at least 30 mg/day for a minimum of 2 weeks; orcorticosteroid-dependent colitis, defined as: an inability to reducecorticosteroids below the equivalent of prednisone 10 mg/day within 3months of starting corticosteroids without a return of signs and/orsymptoms of active UC; or a relapse within 3 months of completing a courseof corticosteroids).
• History of intolerance of corticosteroids (including, but not limited to,Cushing's syndrome, osteopenia/ osteoporosis, hyperglycemia, orneuropsychiatric side-effects, including insomnia, associated withcorticosteroid treatment).
• Immunomodulators: signs and/or symptoms of persistently active diseasedespite at least 3 months treatment with one of the following at locallyapproved doses: oral azathioprine (eg, ≥ 1.5 mg/kg/day) or 6-mercaptopurine (eg, ≥ 0.75 mg/kg/day), or oral azathioprine or 6-mercatopurine within a therapeutic range as judged by thioguaninemetabolite testing, or a combination of a thiopurine and allopurinolwithin a therapeutic range as judged by thioguanine metabolite testing.
• History of intolerance to at least 1 immunomodulator (including but notlimited to nausea/vomiting, abdominal pain, pancreatitis, liver functiontest abnormalities, and lymphopenia) and have neither failed nordemonstrated an intolerance to a biological medication (anti-tumornecrosis factor [TNF] antibody, anti-integrin antibody, or interleukin [IL]-12/23 antagonists) that is indicated for the treatment of UC.

2. Biologic or targeted small molecule therapy failed participants: those whodemonstrated inadequate response or loss of response or intolerance to biologictherapy for UC (eg, anti-TNF antibodies or IL-12/23 antagonists, anti-integrinantibodies) or targeted small molecules (eg, JAK inhibitors or S1P modulators).The therapy used to qualify the participant for entry into this category mustbe approved for the treatment of UC in the country of use, at the time of use.Participants must fulfil one of the following criteria:

• Inadequate response: signs and symptoms of persistently active diseasedespite induction treatment at the approved induction dosing that wasindicated in the product label at the time of use.

• Loss of response: recurrence of signs and symptoms of active diseaseduring approved maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not quality as havingfailed or being intolerant to UC biological therapy, JAK inhibitor, or S1Pmodulators).

• Intolerance: history of intolerance to infliximab, adalimumab, golimumab,vedolizumab, ustekinumab, tofacitinib or other approved biologicals, JAKinhibitors or S1P modulators (including but not limited toinfusion-related event, demyelination, congestive heart failure, or anyother drug-related adverse event that led to a reduction in dose ordiscontinuation of the medication).

• If receiving any of the following therapies, participants must have stable dosagefor the specified duration:

• 5-aminosalicylates (ASAs), stable dosage for ≥ 2 weeks prior to screeningendoscopy.

• Oral corticosteroids: prednisone ≤ 20 mg/day or its equivalent, stable dose for ≥ 2 weeks prior to screening endoscopy.

• Budesonide: extended release tablets 9 mg/day [budensonide MMX], stable dosefor ≥ 2 weeks prior to screening endoscopy.

• Beclomethasone dipropionate: gastro-resistant prolonged-release tablet 5mg/day, stable dose for >= 2 weeks prior to screening endoscopy.

• Conventional immunomodulators: azathioprine, 6-mercaptopurine, methotrexate,stable dosage for ≥ 12 weeks prior to screening endoscopy.

Key Exclusion Criteria:

• Diagnosis of Crohn's disease, inflammatory bowel disease unclassified (indeterminatecolitis), microscopic colitis, ischemic colitis, or clinical findings suggestive ofCrohn's disease.

• Evidence of toxic megacolon, fulminant colitis, intra-abdominal abscess, orstricture/stenosis within the small bowel or colon.

• Participant has had extensive surgery for UC (for example, subtotal colectomy), oris likely to require surgery for the treatment of UC during the study.

• Currently receiving or had treatment within 12 months prior to screening with T celldepleting agents (eg, antithymocyte globulin, Campath).

• Participant has received any of the following prescribed medication or therapywithin the specified time period:

• Anti TNF antibodies (eg, infliximab, adalimumab, golimumab) < 8 weeks prior toscreening rectosigmoidoscopy.

• Anti integrin antibodies (eg, vedolizumab) < 8 weeks prior to screeningrectosigmoidoscopy.

• IL 12/23 antagonist (eg, ustekinumab) < 8 weeks prior to screeningrectosigmoidoscopy.

• JAK inhibitors (eg, tofacitinib) < 4 weeks prior to screeningrectosigmoidoscopy.

• Any other commercially approved biologic agent or targeted small molecule < 8weeks prior to screening rectosigmoidoscopy or < 5 half lives prior toscreening rectosigmoidoscopy, whichever is longer

• Immunomodulatory medications, including oral cyclosporine, intravenouscyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, thalidomide < 4weeks prior to screening rectosigmoidoscopy.

• Any investigational biologic therapy within 8 weeks prior to screeningrectosigmoidoscopy or < 5 half-lives prior to screening rectosigmoidoscopy,whichever is longer.

• Has used apheresis (eg, Adacolumnâ apheresis) < 2 weeks prior to screeningrectosigmoidoscopy.