Safety and Efficacy of TJ301 IV in Participants With Active Ulcerative Colitis

is a multicenter, randomized, double-blind, placebo-controlled phase II study. The trial includes a Run-in Period (if stable conventional treatment needed), a 4-week Screening Period, a 12-week Treatment Period, and a 3-week Safety Follow-up Period to Day 105.

90 patients will be centrally, dynamically, randomly assigned to 3 groups (1:1:1) to receive 600mg TJ301 Q2W, 300mg TJ301 Q2W or placebo Q2W.

Inclusion criteria

• Male and female patients 18-70 (inclusive) years of age.
• Hisory of active UC of more than 3 months. Active UC confirmed by colonoscopy with biopsy or flexible sigmoidoscopy with biopsy at Screening, with extending > 15-cm past the anal verge from endoscopy. Biopsy sample is not necessary if UC is already confirmed.
• Active UC with a full Mayo score≥5 and a rectal bleeding subscore ≥1 at screening.
• During Day -28 to Day -6 prior to Randomisation, an endoscopy subscore ≥2.
• Treated with conventional non-biological UC therapy: with corticosteroids stable for at least 2 weeks prior to Randomization at no more than 20 mg prednisone per day (or equivalent), and/or with medications containing 5-aminosalicylates (5-ASA) at no less than 2 g 5-ASA per day for at least 3 months and stable for at least 4 weeks prior to Randomization, and/or with azathioprine (AZA) at no less than 0.75 mg/kg/day or mercaptopurine (6-MP) at no less than 0.5 mg/kg/day for at least 6 months and stable for at least 6 weeks prior to Randomization, or MTX no less than 12.5 mg/week and stable for at least 12 weeks prior to Randomization.
• Male subjects and female subjects of child bearing potential must have been willing to practice effective contraception during the study and been willing and able to continue contraception for 1 month after their last dose of the study treatment.
• The patient is able and willing to comply with the requirements of this trial protocol.
• The subject should be able to read and write to understand and fill out Patient Diary.
• Voluntarily signed Informed Consent obtained before any trial-related procedures are performed.
• The subject have not received any biologic therapies OR have received 1 biologic drug for the treatment of UC or immune diseases and the last dose must be longer than 8-week or a 5 half-life (whichever is longer) period prior to the first dose of study drug.

Exclusion criteria

• Pregnant or breastfeeding women.
• Contraindication to colonoscopy or sigmoidoscopy.
• Allergies to any component of TJ301.
• Subject who is likely to receive surgery for UC treatment within 1 month based on investigator's evaluation.
• History of colostomy, colectomy or partial colectomy.
• Current diagnosis of inflammatory bowel disease unclassified, Crohn's disease, ischemic colitis, fulminant colitis and/or toxic megacolon, patients with ulcerative colitis limited to the rectum (ulcerative proctitis), infective enteritis, amebic bowel disease or intestinal schistosomiasis.
• History of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. If the Screening colonoscopy shows evidence of dysplasia or a malignancy, the patient is not eligible.
• Primary or secondary immunodeficiency including neutropenia (absolute neutrophil count <1500/μL); or lymphopenia (absolute lymphocyte count <500/μL).
• Moderate to severe anaemia (haemoglobin <9 g/dL), or thrombocytopenia (platelet count <75 000/μL), or serum creatinine >2 mg/dL.
• Autoimmune disease besides UC, with the exceptions of Sjogren's syndrome or hypothyroidism.
• Clostridium (C.) difficile positive at screening visit or treated for C. difficile within the 4 weeks prior to Randomization.
• serum transaminases >2.5 x upper limit of normal [ULN], alkaline phosphatase >2.5 x ULN.
• Serious underlying disease other than UC in the opinion of the investigator.
• History of drug addiction within the last 1 year or current drug addiction or use of illicit drugs.
• Any indication of the regular use of more than 40 grams of alcohol every day.
• Smokers who smoke more than 10 cigarettes per day.
• Known concurrent acute or chronic viral hepatitis B or C infection or human immunodeficiency virus (HIV) infection.
• Presence or history of active tuberculosis (TB) or latent TB infection, defined as 1) a positive QuantiFERON-TB Gold test at Screening; or 2) a T-spot test within 4 weeks of Randomisation and evidence of current or previous pulmonary tuberculosis by low-dose CT or chest X-ray within 12 weeks of Randomisation. Patients with old TB will also be excluded.
• Positive immunoglobulin M antibody titres to Epstein-Barr virus (EBV).
• Subjects with positive results for cytomegalovirus at screening are to be excluded.
• Receiving any investigational therapy or any approved therapy for investigational use within 30 days or 5 half-lives prior to Randomization (whichever is longer).
• Currently taking any medications other than those allowed per protocol guidelines.
• Infections (including diverticulitis) requiring treatment with antibiotics, antivirals, or antifungals within 14 days prior to Randomisation.
• Received any live (attenuated) vaccines within 30 days prior to Randomisation.
• Recent treatment with medium-to-high-dose intravenous corticosteroids (methylprednisolone 60 mg/day or hydrocortisone 300 mg/day) within 8 weeks prior to Randomisation or oral corticosteroids of more than 20 mg prednisone per day (or equivalent).
• Receipt of cyclosporine, tacrolimus, sirolimus, thalidomide, or mycophenolate mofetil within 30 days prior to Randomisation.
• Treatment with therapeutic enema or suppository, other than required for endoscopy preparation, within 14 days prior to the screening endoscopy and during the remainder of the trial.