Clinical Study in Active Ulcerative Colitis

Prior treatment

• Use of antibiotics (except for local use), prebiotics, or probiotics ≤4 weeks prior to randomization or anticipated during study participation, or concomitant, chronic use of an antidiarrheal drug, or concomitant use of any rectal treatment.
• Use of fecal microbiota transplantation ≤52 weeks prior to randomization
• Treatment with another investigational drug or intervention within 30 days prior to Screening, or within 5 times the elimination half-life of the investigational drug (whichever is longest).
• Evidence of a clinically significant, active infection of the gastrointestinal tract or of any other organ system at Screening, unless deemed benign. Clostridium difficile infection should have had adequate treatment and a negative toxin test prior to Screening endoscopy.
• Previous use of any advanced UC treatment, including any anti-tumor necrosis factor, anti-integrin or anti-interleukin (IL)-12/23 agent, anti-IL23, Janus kinase inhibitors, and sphingosine-1-phosphate receptor modulators.
• Use of sulfasalazine ≤4 weeks prior to randomization.
• Use of corticosteroids or any disease-modifying antirheumatic drug, including thiopurines, ≤6 weeks prior to randomization into the study, except for a stable, low dose of oral corticosteroids (≤10 mg prednisolone/day) for at least 2 weeks prior to Screening colonoscopy and up to at least the Week 12 visit.

Other illness

• Diagnosis of Crohn’s disease, undetermined colitis, ischemic colitis, fulminant colitis, or toxic megacolon.
• Any immunocompromised state, including eg, active human immunodeficiency virus infection, malignancies, liver cirrhosis, systemic chemotherapy).
• Ongoing or recent (<3 months) severe renal disease or insufficiency as manifested, eg, by medical history and/or clinical examination and/or (calculated or measured) glomerular filtration rate ≤60 mL/min.
• Clinically significant bone marrow disease if progressive or not controlled, or any history of solid organ or bone marrow transplantation.
• Any protein-losing enteropathy (any cause), any granulomatous disease, any systemic (autoimmune) disease if progressive or not controlled (uncomplicated and well-controlled diabetes mellitus is allowed).
• Active intravenous drug abuse or alcohol abuse disorder as assessed by the Investigator
• Participants who are inappropriate for the study per the Investigator’s discretion, including: • Participants with any other condition, disorder, or disease that in the Investigator’s judgment would make the participant unsuitable for inclusion in the study • Participants with a hypersensitivity to drugs with a similar mechanism as well as known allergy/hypersensitivity to any component of the study treatment, including any of the excipients • Participants who in the opinion of the Investigator are not likely to complete the study for whatever reason • Participants who are unwilling or unable to comply with protocol requirements, including eg, complete the full course of study treatment per schedule, attend study visits and all required assessments/investigations, and complete all questionnaires and e-diary using their personal device or study-provided device
• Total colectomy, stoma or ileo-anal pouch, or history of extensive colonic resection leaving less than 30 cm of colon
• Presence of intra-abdominal fistula, abscesses, diverticulitis, or gastrointestinal bleeding unrelated to UC
• History of colon carcinoma or high-grade dysplasia

Lab values

• Leukopenia (total white blood cell count <3000/µL) and/or neutropenia (absolute neutrophil count <1000/µL), anemia (hemoglobin <10.0 g/dL), thrombocytopenia (peripheral blood platelet count <100 × 10E9/L), and/or any coagulation disorder with significantly increased risk of bleeding. For any of these exclusion criteria at Screening, 1 retest is allowed.
• Ongoing or recent (<3 months) advanced hepatic dysfunction defined as a Child Pugh score ≥10 (Class C) or increase ≥2 times the upper limit of normal in AST, ALT, total bilirubin (TB), prothrombin time (PT), or international normalized ratio (INR).

Other

• Pregnancy or lactation at study entry
• An employee (or a relative of) of the Investigator, study center, contract research organization, or Sponsor
• Severe UC (mMS>7), meeting modified Truelove Witts' criteria and/or RB score of 3, participant with ulcerative proctitis only, or participant in whom colitis is most severe in the transverse colon or ascending colon, or if any hospitalization is planned at the time of Screening

• Male or female aged ≥16 years (≥18 years for Czech Republic) of age at time of signing the consent/assent. Enrollment of participants <18 years old should only occur if acceptable by local laws and regulations.
  • OLE 3. Having had no significant safety concerns during the Induction Phase, as determined by the Investigator.
  • OLE 4. FOCBP must agree to continue using an acceptable contraceptive method in countries where this is required
• Documented diagnosis (histologic diagnosis and either endoscopic or radiographic diagnosis) of UC at least 3 months prior to Screening (a biopsy report supporting the histologic diagnosis must be available).
• Diagnosis of active mild-to-moderate UC at Screening as defined by an mMS of 4 to 7, including a MES ≥2 (confirmed by central reading), a Mayo RB score of 1 or 2, and a Mayo Stool Frequency score ≥1.
• UC lesions extending ≥10 cm from the anal verge.
• Participant must either: • receive a stable dose of orally administered 5 ASA ≥4 weeks prior to randomization and continue the same regimen during the entire study (including OLE phase), or • have failed, due to insufficient efficacy, oral 5-ASA induction treatment at a minimum dosage of 2 g/day for at least 6 weeks or have failed oral 5-ASA maintenance treatment at a minimum dosage of 2 g/day, or • have a documented intolerance or poor tolerance to an aminosalicylic acid treatment, including 5-ASA, or be contra-indicated to receive 5 ASA treatment per local labeling
• Participant must provide written informed consent or assent.
• In countries not allowing females of childbearing potential (FOCBP) to participate without an acceptable contraceptive method, the FOCBP must agree to abide to local requirements and eg, use at least an acceptable method of contraception until the end of treatment
  • OLE 1. Having successfully completed the Week 12 visit of the Induction Phase ie, having demonstrated acceptable compliance per the Investigator’s discretion and having completed patient-reported assessments.
  • OLE 2. Participant must be willing and agree to abide to the study requirements, including compliance with study treatment administration, attendance to study visits, performing assessments, including collection of patient-reported data via their personal device (BYOD), and providing stool samples.