a study to assess the safety and efficacy of lb-p8 in patients with psc

Conditions: Primary Sclerosing Cholangitis (PSC)

Summary: the study is designed to assess the safety and efficacy of lb-p8 in patients with primary sclerosing cholangitis.

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.

Eligibility criteria:
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

Keywords: psc pruritus inflammatory bowel disease ibd itch cholestasis