Evaluation of Norucholic Acid in the Treatment of Primary Sclerosing Cholangitis: An Open-Label Study

The primary objective of this study is to evaluate the **safety** and **tolerability** of norucholic acid (NCA) film-coated tablets in the treatment of **Primary Sclerosing Cholangitis (PSC)**. This is clinically relevant as PSC is a chronic liver disease characterized by inflammation and scarring of the bile ducts, which can lead to liver damage and failure. Assessing the safety and tolerability of NCA is crucial for determining its potential as a therapeutic option for patients with PSC.

Secondary objectives include:

• To assess the efficacy of NCA in patients with PSC.

The clinical trial involves a total of **25 participants** diagnosed with **Primary Sclerosing Cholangitis (PSC)**. The study population includes both **males and females** aged 18 years and older. Participants were selected based on their previous involvement in the NUC 5/PSC trial, with specific criteria regarding the completion or premature termination of the DBE phase. The trial includes individuals who are considered part of a vulnerable population. Participants are required to have signed informed consent. Women of childbearing potential must adhere to stringent contraceptive measures throughout the study and for a specified period after the last dose. The trial aims to evaluate the safety and tolerability of norucholic acid (NCA) film-coated tablets in treating PSC.

The clinical trial is designed to evaluate the **safety** and tolerability of **norucholic acid** film-coated tablets in the treatment of **Primary Sclerosing Cholangitis (PSC)**. This is an open-label, therapeutic exploratory and confirmatory clinical trial. The study will involve adult participants who have previously been diagnosed with PSC and have participated in a prior related trial. The trial is expected to commence recruitment on January 31, 2025, and conclude by September 30, 2027, with a maximum treatment period of 72 weeks.

Participants will be administered norucholic acid orally, with a maximum daily dose of 1500 mg. The trial will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess overall outcomes. The primary endpoints include the occurrence of treatment-emergent adverse events (TEAEs), serious TEAEs, severe TEAEs, adverse drug reactions (ADRs), and unexpected TEAEs. Secondary endpoints will assess changes in vital signs, body weight, hematology, serum chemistry, urinalysis, liver stiffness, and s-ALP levels from baseline to the end of treatment.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including the occurrence of severe adverse events or lack of efficacy as defined in the previous trial. The trial will adhere to strict eligibility criteria, including informed consent and appropriate contraceptive measures for women of childbearing potential. The study aims to provide valuable insights into the therapeutic potential of norucholic acid for patients with PSC.

The clinical trial involves the administration of **norucholic acid**, an experimental medication, in the form of a **film-coated tablet**. The active substance, norucholic acid, is a synthetic C23 homologue of the 3α,7β-dihydroxy C24 bile acid ursodeoxycholic acid. The pharmaceutical form is a film-coated tablet, designed for **oral use**. The maximum daily dose of norucholic acid is 1500 mg, with a total maximum dose of 756 g over the course of the treatment period, which spans up to 72 weeks. The medication is manufactured by Dr. Falk Pharma G.M.B.H. and is not a pediatric formulation. The trial aims to evaluate the safety and tolerability of norucholic acid in patients with **Primary Sclerosing Cholangitis (PSC)**.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of norucholic acid. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. The trial is open-label, meaning both the researchers and participants are aware of the treatment being administered. The orphan drug designation has been granted for this medication, indicating its potential benefit in treating a rare condition.

Efficacy in the clinical trial evaluating **Primary Sclerosing Cholangitis (PSC)** treatment with norucholic acid tablets will be assessed through specific secondary endpoints. These endpoints include the course of liver stiffness and changes in serum alkaline phosphatase (s-ALP) levels from baseline to the end of treatment (EoT). The assessment of liver stiffness and s-ALP levels will provide insights into the therapeutic impact of norucholic acid on liver function and disease progression in patients with PSC. The collection and analysis of these efficacy parameters will be conducted at predetermined timepoints throughout the trial, ensuring a comprehensive evaluation of the treatment's effectiveness. The use of validated laboratory tests and measurement techniques will ensure the reliability and accuracy of the data collected. The trial is designed to provide robust evidence on the efficacy of norucholic acid in managing PSC, contributing to the understanding of its potential benefits in this patient population.