Open Label Study to Evaluate Safety and Efficacy of LUM001 in Patients With Primary Sclerosing Cholangitis

Study Overview
=================
Brief Summary
-----------------
The study is an open-label study in adults with primary sclerosing cholangitis to evaluate the safety, tolerability, and effect of 14-weeks of daily dosing of LUM001.

Official Title
-----------------
A Pilot, Open-Label Study to Evaluate the Safety, Tolerability and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in Patients With Primary Sclerosing Cholangitis

Conditions
-----------------
Primary Sclerosing Cholangitis (PSC)

Intervention / Treatment
-----------------
* Drug: LUM001


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects between the ages of 18-80 years, inclusive. Diagnosis of PSC If inflammatory bowel disease (IBD) is present, disease activity ≤ 2 (normal to moderate), using the physician assessment on the Mayo ulcerative colitis (UC) disease activity score. Patients receiving azathioprine for intestinal bowel disease are eligible to participate in the study provided that they have had no IBD exacerbations for at least 6 months. Females of childbearing potential must have a negative serum pregnancy test [β human chorionic gonadotropin (β-hCG)] during screening and negative urine pregnancy test at the baseline/Day 0 visit. Sexually active females must be postmenopausal, surgically sterile, or if premenopausal, be prepared to use an effective method (≤ 1% failure rate) of contraception during the trial. Ability to read and understand English in order to use the study-related questionnaires and the text on the eDiary screen. Must be willing and able to use an eDiary daily for a minimum of 20 weeks. Must digitally accept the licensing agreement in the eDiary software at the outset of the study. Must complete at least 10 eDiary Adult ItchRO reports (AM or PM) during each of two consecutive weeks of the screening period prior to allocation to treatment (maximum possible reports = 14 per week). Access to phone for scheduled calls from study site. Must agree to comply with the study protocol procedures and provide written informed consent. Exclusion Criteria: Small duct PSC (clinical biochemical and histological features compatible with PSC, but having a normal cholangiogram). Presence of a dominant stricture unless brushings and/or biopsies of the stricture are negative for dysplasia or malignancy within 6 months of screening. Surgical or endoscopic biliary tree interventions for treatment of clinically significant strictures within 6 months of screening. IBD flare (Mayo UC disease activity score > 5 including endoscopic evaluation) within 3 months prior to screening. Secondary cause of sclerosing cholangitis (e.g., choledocholithiasis, post-surgical biliary stricture, intra-arterial chemotherapy, recurrent pancreatitis, IgG4 associated cholangiopathy, AIDS cholangiopathy). AST or ALT ≥ 5 x ULN at screening. History or presence of any other concomitant significant liver disease as assessed by the Investigator. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease). Known history of human immunodeficiency virus (HIV) infection. The anticipated need for a surgical procedure within 20 weeks from randomization. Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of randomization. History of cancer, except for basal or squamous cell carcinoma of the skin, or with any laboratory or physical exam or diagnostic procedure finding suggestive of current malignancy. Family history of any documented hereditary cancer syndrome. History of alcohol or other substance abuse within 1 year prior to screening. Receipt of an investigational drug, biologic, or medical device within 30 days prior to Screening, or 5 half-lives of the study agent, whichever is longer. History of noncompliance with medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to noncompliance with the study protocol. Any other conditions or abnormalities which, in the opinion of the Investigator or Medical Monitor, may compromise the safety of the subject, or interfere with the subject participating in or completing the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LUM001<br>LUM001 administered orally once each day | Drug: LUM001<br>* LUM001 oral dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An Adverse Event (AE) was defined as any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered to be related to the investigational drug product. TEAEs were AEs with a start date on or after the first dose of investigational product and started prior to the last dose of investigational product plus 14 days. | From start of study drug administration until Week 18 | 
| Change From Baseline in Fasting Serum Bile Acid Level at Week 14 | Serum bile acid levels were evaluated using blood samples collected. | Baseline, Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Liver Enzyme Levels in Serum | Levels of liver enzymes such as Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP) in serum were evaluated. | Baseline, Week 14 | 
| Change From Baseline in Bilirubin Levels at Week 14 | Total Bilirubin and Direct (Conjugated) Bilirubin levels were evaluated. | Baseline, Week 14 | 
| Change From Baseline in Pruritus as Measured by Adult Itch Reported Outcome (ItchRO) Weekly Sum Score | The Adult ItchRO instrument was completed twice daily using an electronic diary (eDiary). Each morning and evening score had a range from 0-10, with the higher score indicating increasing itch severity. The following was used for assessing the Adult ItchRO daily score: The score which represented the most severe itching for the day (morning or evening) was taken for each day as the daily score (maximum daily score of 10); If only 1 of the 2 scores was available for the day, the score that was available was used as the daily score; If both the morning and the evening scores were missing, the score was considered missing for the day. | Baseline, Week 14 |