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

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

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.

Inclusion Criteria:

1. Male or female subjects between the ages of 18-80 years, inclusive.
2. Diagnosis of PSC
3. 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.
4. 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.
5. 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.
6. 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.
7. Ability to read and understand English in order to use the study-related questionnaires and the text on the eDiary screen.
8. Must be willing and able to use an eDiary daily for a minimum of 20 weeks.
9. Must digitally accept the licensing agreement in the eDiary software at the outset of the study.
10. 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).
11. Access to phone for scheduled calls from study site.
12. Must agree to comply with the study protocol procedures and provide written informed consent.

Exclusion Criteria:

1. Small duct PSC (clinical biochemical and histological features compatible with PSC, but having a normal cholangiogram).
2. Presence of a dominant stricture unless brushings and/or biopsies of the stricture are negative for dysplasia or malignancy within 6 months of screening.
3. Surgical or endoscopic biliary tree interventions for treatment of clinically significant strictures within 6 months of screening.
4. IBD flare (Mayo UC disease activity score > 5 including endoscopic evaluation) within 3 months prior to screening.
5. Secondary cause of sclerosing cholangitis (e.g., choledocholithiasis, post-surgical biliary stricture, intra-arterial chemotherapy, recurrent pancreatitis, IgG4 associated cholangiopathy, AIDS cholangiopathy).
6. AST or ALT ≥ 5 x ULN at screening.
7. History or presence of any other concomitant significant liver disease as assessed by the Investigator.
8. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget's disease).
9. Known history of human immunodeficiency virus (HIV) infection.
10. The anticipated need for a surgical procedure within 20 weeks from randomization.
11. Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of randomization.
12. 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.
13. Family history of any documented hereditary cancer syndrome.
14. History of alcohol or other substance abuse within 1 year prior to screening.
15. 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.
16. 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.
17. 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.