A Study to Assess the Safety and Efficacy of LB-P8 in Patients With PSC

This is phase 2, randomized, double-blind, placebo-controlled, multicenter study to assess the safety and efficacy of LB-P8 in adult patients with primary sclerosing cholangitis(PSC).

• Part 1 will evaluate safety and tolerability of 2 pre-selected dose level of LB-P8 (low-dose[1×10^10 CFU/capsule] and high dose [1×10^11 CFU/capsule]) in adult patients with PSC. Part 1 plans to enroll a maximum number of 12 patients based on a "3+3" study design.
• Part 2 will evaluate safety and efficacy in adult patients with PSC. Eligible patients with PSC will be randomized in a 1:1:1 ratio to receive treatment with low-dose LB-P8(1×10^10 CFU/capsule), high-dose LB-P8(1×10^11 CFU/capsule) or matched placebo capsule. Part 2 plans to enroll and randomize 75 patients to obtain 60 evaluable patients.

Inclusion criteria

• Age: 18 to 75 years
• A diagnosis of PSC based on cholangiographic evidence of PSC in accordance with American Association for the Study of Liver Diseases (AASLD) guidelines
• ALP >1.5 times the ULN at screening
• PSC with or without IBD, such as ulcerative colitis or Crohn's disease
• If patients are being administered biologic or advanced therapeutic treatments, immunosuppressants, systemic corticosteroids, obeticholic acid, fibrates, or statins, they must be on a stable dose for ≥3 months prior to, and including, Day 0 and plan to remain on a stable dose throughout the study
• If patients are receiving ursodeoxycholic acid, they must be on a stable dose (not exceeding 23 mg/kg/day) for >3 months prior to screening
• Patient agrees to stop all probiotics for at least 2weeks prior to treatment
• Patient is unable to conceive and/or patient who's partner is unable to become pregnant and/or agree to use effective methods of contraception when engaging in heterosexual intercourse

Exclusion criteria

• Treatment with any investigational agents within 3 months or 5 half-lives, whichever is longer prior to treatment or during the study. Gene therapy or other long-lasting investigational agents with unknown half-life is not allowed
• History of a liver transplant or anticipated need for a liver transplant within 1 year
• Patients who show evidence of significant worsening of hepatic function will be excluded.
• Evidence of compensated or decompensated cirrhosis based on histology, relevant medical complications, or laboratory parameters
• Model for end-stage liver disease (MELD) score as below, unless the MELD is driven by anticoagulant therapy, vitamin deficiency, or kidney disease:
• MELD Score of >12 (decompensated cirrhosis) for Part 1 of the study
• MELD Score of >12 for Part 2 of the study
• Small-duct PSC (in the absence of large duct PSC)
• Secondary causes of sclerosing cholangitis including IgG4 associated sclerosing cholangitis
• Any history of cholangiocarcinoma, gallbladder cancer, or hepatocellular carcinoma
• History of any malignancy with lymph node or regional metastases within 5 years or current malignancy undergoing active treatment
• Patients who require chronic use of antibiotics, received antibiotics in the last 1 month, or received Rebyota or Vowst (applicable for patients with Clostridioides difficile infection)
• In patients with ulcerative colitis, partial Mayo score of >6 or, patients with Crohn's disease if CDAI of >220
• Chronic kidney injury
• Recent acute cholangitis (within 90 days)
• Patients with indwelling biliary drain (or stent), total proctocolectomy with ileal anal pouch, partial large bowel resections or history of small bowel resection
• Other causes of liver disease, such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), AIH/PSC overlap syndrome, alpha-1-antitrypsin deficiency, viral hepatitis, iron overload syndrome, Wilson disease, nonalcoholic steatohepatitis, and/or alcohol related liver disease. Additionally, positive serology for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti HCV) (detectable HCV RNA in the serum), or human immunodeficiency virus antibodies (anti HIV)
• Active drug (known or suspected use of illicit drugs or drugs of abuse) or alcohol abuse disorder
• Female patients who are pregnant, nursing, or planning to become pregnant during the study
• Clinically significant and/or active infection
• Subjects with a greater degree of immunosuppression, as evidenced by Alsolute neutrophil count <500 cells/mL or in the investigator's judgement immunosuppressed and at higher risk of infection