A phase 2a trial to evaluate the safety and tolerability of LUM001 in subjects with Primary Sclerosing Cholangitis (PSC) during 14 weeks of treatment.
- Conditions
- MedDRA version: 17.1Level: LLTClassification code 10036732Term: Primary sclerosing cholangitisSystem Organ Class: 100000004871Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology.PSC is characterized by inflammation and fibrosis of the intra- and extrahepatic biliary tree resulting in diffuse multifocal stricture formation leading to biliary cirrhosis, portal hypertension and liver failure. PSC is a life-threatening and debilitating disease. The median survival from diagnosis in symptomatic patients with PSC has been estimated to be 12 years.
- Registration Number
- EUCTR2014-005558-21-GB
- Lead Sponsor
- umena Pharmaceuticals LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 20
To participate in this study subjects must meet all of the following criteria:
1. Male or female subjects between the ages of 18-80 years, inclusive.
2. Diagnosis of PSC consistent with American Association for the Study of Liver Disease (AASLD) (Chapman, et al., 2010), which includes the documented history of the following diagnostic factors:
a. Alkaline phosphatase >1.5 x ULN.
b. Magnetic resonance cholangiography (MRC), or endoscopic retrograde cholangiography (ERC), or percutaneous transhepatic cholangiography (PTC) demonstrating intrahepatic and/or extrahepatic biliary obstruction, beading, or narrowing consistent with PSC.
c. If liver biopsied previously, histological findings with features consistent with or diagnostic 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 [ß human chorionic gonadotropin (ß-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. Effective methods of contraception are considered to be:
a. Hormonal (e.g., contraceptive pill, patch, intramuscular implant or injection) provided subject has been on stable therapy for at least 3 months; or
b. Barrier method, i.e., (a) condom (male or female) or (b) diaphragm, with spermicide; or
c. Intrauterine device (IUD); or
d. Vasectomy (partner).
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 5
Subjects will be excluded from the study if they meet any of the following 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, including:
a. Hepatitis B infection (HBsAg positive).
b. Hepatitis C infection (antibody positive); patients with a positive antibody test will be eligible if there is documented history of negative HCV RNA and not previously treated for HCV.
c. Any other cholestatic liver disease [e.g., primary biliary cirrhosis (PBC)].
d. Alcoholic liver disease.
e. Proven overlap autoimmune hepatitis.
f. Proven non-alcoholic steatohepatitis (NASH).
8. Presence of advanced clinical complications of PSC or clinically significant hepatic decompensation, including:
a. History of liver transplantation, current placement on a liver transplant list or current Model for End Stage Liver Disease (MELD) score = 15.
b . Hepatic encephalopathy.
c . Hepatorenal syndrome (type I or II) or screening serum creatinine >2.00 mg/dL (177 µmol/L).
d. Recurrent variceal bleeding.
e. Refractory ascites.
9. History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine [e.g., untreated celiac disease, terminal ileum resection, or gastric bypass procedures (gastric lap band is acceptable) cystic fibrosis, Wilson’s disease.
10. Medical conditions that may cause nonhepatic increases in ALP (e.g., Paget’s disease).
11. Known history of human immunodeficiency virus (HIV) infection.
12. The anticipated need for a surgical procedure within 20 weeks from randomization.
13. Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of randomization.
14. 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.
15. Family history of any documented hereditary cancer syndrome.
16. History of alcohol or other substance abuse within 1 year prior to screening.
17. Administration of the following medications:
a. Within 12 months prior to treatment: rituximab.
b . Within 6 months prior to treatment: hydroxychloroquine, methotrexate, oral vancomycin, colchicine, bezafibrate/fenofibrate, anti-TNF therapies, leflunomide, tocilizumab, or = 10 mg prednisone (or equivalent); (topical, inhaled, or short course therapy for intercurrent illness are permitted).
c. Within 28 days prior to treatment: UDCA, bile acid resins.
18. Receipt of an investigational drug, biologic, or medic
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method