Primary Sclerosing Cholangitis (PSC)
Conditions
Keywords
PSC, Pruritus, Inflammatory bowel disease, IBD, Itch, Cholestasis
Brief summary
The study is designed to assess the safety and efficacy of LB-P8 in patients with primary sclerosing cholangitis.
Detailed description
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.
Interventions
DRUGLB-P8 low-dose
One capsule QD (1×10\^10 CFU/day) oral administration
DRUGLB-P8 high-dose
One capsule QD (1×10\^11 CFU/day) oral administration
DRUGPlacebo
One capsule QD oral administration
Sponsors
LISCure Biosciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability of 2 different doses of LB-P8 | (Part 1) Up to 4 weeks of treatment from the Baseline | Occurrence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) by CTCAE V5.0 |
| Safety and tolerability of LB-P8 | (Part 2) Up to 24 weeks of treatment from the Baseline | Occurrence of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) by CTCAE V5.0 |
| Mean percent change from baseline in Serum Concentrations of Alkaline Phosphatase (ALP) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in biliary metrics (biliary strictures and dilatations) | (Part 2) Up to 24 weeks of treatment from the Baseline | Biliary metrics (biliary strictures and dilatations) will be assessed by magnetic resonance cholangiopancreatography (MRCP) |
| Changes from baseline in liver stiffness | (Part 2) Up to 24 weeks of treatment from the Baseline | Liver stiffness will be measured by transient elastography (FibroScan®) |
| Change from baseline in alanine aminotransferase (ALT) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in aspartate aminotransferase (AST) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in gamma glutamyl transferase (GGT) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Percentage of patients who achieve ALP of <1.5 × upper limit of normal (ULN) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in international normalized ratio (INR) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in total and direct bilirubin | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in fasting serum bile acid level | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| The percentage of patients who experience liver disease progression | (Part 2) Up to 24 weeks of treatment from the Baseline | The percentage of patients who experience progression to cirrhosis, clinical decompensation rates, liver transplant, newly diagnosed cholangiocarcinoma, MELD score increase from \<12 to \>15 and Death from any cause |
| Change from baseline in prothrombin time (PT) and partial prothrombin time (PTT) | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in ALP | (Part 2) Up to 24 weeks of treatment from the Baseline | — |
| Change from baseline in enhanced liver fibrosis (ELF™) | (Part 2) Up to 24 weeks of treatment from the Baseline | Hyaluronic acid, procollagen-3 N-terminal peptide, and a tissue inhibitor of metalloproteinase 1 will be assessed in blood for ELF test. |
Countries
United States
Contacts
Primary ContactLISCure Biosciences Clinical Trials
Outcome results
None listed