Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of EP547 in Subjects with Cholestatic Pruritus Due to Primary Biliary Cholangitis or Primary Sclerosing Cholangitis
- Conditions
- Cholestatic PruritusCholangitis10019654
- Registration Number
- NL-OMON53412
- Lead Sponsor
- Escient Pharmaceuticals, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 2
1. Age 18 to 80 years, inclusive
2. Has experienced self-reported daily or near-daily moderate to severe
pruritus before Screening
3. Has a mean daily WI-NRS score indicative of moderate to severe pruritus
(score >=4) as recorded using a study-issued electronic device or application
(app) during Screening (Day -7 through Day -1); data from at least 4 of the 7
days are required to be considered an acceptable profile
4. If currently taking medications to treat the cholestatic disorder
(obeticholic acid [OCA]), must be on a stable dose for >12 weeks before
Screening and plans to maintain the regimen throughout the study
5. If currently taking a fibrate, must be on a stable dose for >12 weeks before
Screening and plans to maintain the regimen throughout the study
6. Either is not treated with or has been on a stable regimen with any
medications to treat pruritus for >4 weeks before Screening and plans to
maintain the regimen throughout the study
7. If female, must have a negative serum pregnancy test at Screening and be
willing to not donate eggs from Screening until the last dose of study drug
8. Must be able to communicate well with the Investigator, understand and
comply with the requirements of the study, and understand and provide written
consent
9. For subjects with concomitant inflammatory bowel disease (IBD): a.
Colonoscopy (if subject has a colon) or other appropriate endoscopic procedure
within 18 months of Day 1 confirming no dysplasia or colorectal cancer b.
Subjects with Crohn*s disease (CD) must be in remission as defined by a Crohn*s
Disease Activity Index (CDAI) <150 at Screening c. Subjects with ulcerative
colitis (UC) must have a Partial Mayo Scoring Index score<=3 with no individual
sub-score exceeding 1 point at Screening
10. Documented history of PBC that is consistent with the American Association
for the Study of Liver Diseases (AASLD) Practice Guidelines (Lindor 2019),
defined as having >=2 of the following 3 factors upon diagnosis: a. History of
elevated alkaline phosphatase (ALP) levels b. Historic positive
antimitochondrial antibody (AMA) or AMA-M2 by immunofluorescence, enzyme linked
immunosorbent assay (ELISA), or immunoblot or if AMA is negative, positive for
PBC-specific antibodies (anti-GP210 and/or anti-SP100) c. Liver histology at
any point in time consistent with PBC
11. If currently taking ursodeoxycholic acid (UDCA), must be treated for >=1
year, and must be on a stable dose of not more than 20 mg/kg/day for >=12 weeks.
If not currently taking UDCA, must not be treated with UDCA within 12 weeks
before Screening or plan to be treated with UDCA during the study
12. Documented history of PSC based on either cholangiography (ie, magnetic
resonance cholangiopancreatography, endoscopic retrograde
cholangiopancreatography, or percutaneous transhepatic cholangiogram) or if
small duct PSC, confirmed by typical histologic evidence of PSC for >=1 year
13. If currently taking UDCA, must be treated for >=1 year, and must be on a
stable dose of not more than 23 mg/kg/day for >=12 weeks. If not currently
taking UDCA, must not be treated with UDCA within 12 weeks before Screening or
plan to be treated with UDCA during the study.
1.Pruritus is attributed mainly to any disease unrelated to PBC or PSC
2.Prior liver transplant or presently listed for transplantation
3.Is receiving ongoing ultraviolet B (UVB) treatment or plasmapheresis or
anticipates receiving such treatments during the study
4.Evidence of compensated or decompensated cirrhosis based on ANY of the
following: Historical liver biopsy demonstrating cirrhosis b. Liver stiffness
as assessed by a FibroScan® score of >=16.9 kPa for subjects with PBC or >=14.4
kPa for subjects with PSC within 6 months of Screening c. History or presence
of portal hypertension with complications, including known gastric or
esophageal varices, ascites, spontaneous bacterial peritonitis, hepatic
encephalopathy, history of variceal bleeds, or related therapeutic or
prophylactic interventions
5.History of malignancy of any organ system, including but not limited to
hepatocellular carcinoma, cholangiocarcinoma, and gall bladder carcinoma,
treated or untreated, within the past 5 years (localized squamous cell or basal
cell carcinoma of the skin that have been excised or resolved is not
exclusionary)
6.Alternate causes of liver diseases such as hepatic sarcoidosis, alcoholic
liver disease, histology confirmed autoimmune hepatitis, overlap hepatitis, or
nonalcoholic steatohepatitis (NASH), or uncontrolled viral hepatitis as defined
in Protocol
7.Presence of documented secondary sclerosing cholangitis (eg, ischemic
cholangitis, recurrent pancreatitis, intraductal stone disease, severe
bacterial cholangitis, surgical or blunt abdominal trauma, recurrent pyogenic
cholangitis, choledocholithiasis, toxic sclerosing cholangitis due to chemical
agents, or any other cause of secondary sclerosing cholangitis) on prior
clinical investigations
8.Immunoglobulin G4 (IgG4) >4× upper limit of normal (ULN) at Screening or
evidence of systemic IgG4-related disease
9.Current evidence of clinically significant high-grade strictures or presence
of biliary stent at Screening
10.History of recurrent bacterial cholangitis or recent episode within 3 months
before Screening 11.Endoscopic interventions with therapeutic intent such as
biliary duct dilation within 3 months before Screening or planned during the
study
12.History of significant small bowel resection or short bowel syndrome
13.Presence of a concomitant disease or a history of any medical condition
that, in the opinion of the Investigator, could pose undue risk to the subject,
impede completion of the study procedures, or would compromise the validity of
the study measurements
14.Clinically relevant medical history, physical examination, vital sign,
standard 12-lead electrocardiogram (ECG), chemistry, hematology, urinalysis, or
coagulation results at Screening beyond what is expected for subjects with a
cholestatic disorder that would place the subject at undue risk as deemed by
the Investigator
15.Has any of the following laboratory results at Screening: a.Total bilirubin
>2.0 mg/dL; total bilirubin >2.0 mg/dL is acceptable for subjects with
medically documented Gilbert*s syndrome if direct bilirubin is <0.3 mg/dL
b.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5× ULN
c.ALP >10× ULN d.International normalized ratio (INR) >1.3 e.Platelet count
<150,000/µL f.Urine albumin to c
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary estimand of the study is to assess the difference in severity of<br /><br>pruritus in subjects with cholestatic pruritus due to PBC or PSC treated with<br /><br>EP547 or placebo, as measured by change in weekly average WI-NRS after 6 weeks<br /><br>of randomized treatment, regardless of treatment discontinuation and use of<br /><br>prohibited and/or rescue medications.</p><br>
- Secondary Outcome Measures
Name Time Method <p>na</p><br>