Clinical trial NCT02653625: PERSEUS: Preliminary Efficacy and Safety of Cenicriviroc in Adult Participants With Primary Sclerosing Cholangitis
Official title: PERSEUS: A Phase 2 Proof of Concept Study Investigating the Preliminary Efficacy and Safety of Cenicriviroc in Adult Subjects With Primary Sclerosing Cholangitis (PSC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Sclerosing Cholangitis
Keywords: Primary Sclerosing Cholangitis
Lead sponsor: Tobira Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-01-12
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open label, proof of concept (PoC) study of Cenicriviroc (CVC) in adult participants with Primary Sclerosing Cholangitis (PSC). The main objective of this PoC study is to assess changes in alkaline phosphatase (ALP) both individually and as a group, over 24 weeks of treatment with CVC.


Eligibility criteria: Inclusion Criteria:

* Participants with chronic cholestatic liver disease for at least 6 months
* Clinical diagnosis of Primary Sclerosing Cholangitis (PSC) as evident by chronic cholestasis of more than six months duration with either a consistent magnetic resonance cholangiopancreatography (MRCP)/endoscopic retrograde cholangiopancreatography (ERCP) showing sclerosing cholangitis, or a liver biopsy taken at any time consistent with PSC in the absence of a documented alternative etiology for sclerosing cholangitis. If diagnosis of PSC was made by histology alone, it must require the presence of fibro-obliterative lesions (i.e., onion skin lesions)
* Participants with or without Inflammatory Bowel Disease (IBD) are allowed. If participant has IBD, documented evidence of IBD either by prior endoscopy or in previous medical records, for ≥ 6 months. In addition, participants will be required to enter the study with a Partial Mayo Risk score of 0-3, inclusively
* In participants receiving treatment with ursodeoxycholic acid (UDCA), therapy must be stable for at least 3 months, and at a dose not greater than 20 mg/kg/day
* Serum ALP greater than 1.5 × upper limit of normal (ULN)
* Ability to understand and sign a written informed consent form (ICF)
* Participants receiving allowed concomitant medications need to be on stable therapy for 28 days prior to the Baseline Visit with the exception of UDCA in which participants need to be on stable therapy for ≥ 3 months

Exclusion Criteria:

* Presence of documented secondary sclerosing cholangitis (such as 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
* Small duct PSC
* Presence of percutaneous drain or bile duct stent
* History of cholangiocarcinoma or high clinical suspicion over dominant stricture within 1 year by MRCP/ERCP or clinical judgment
* Ascending cholangitis within 60 days prior to Screening
* Alcohol consumption greater than 21 units/week for males or 14 units/week for females (one unit of alcohol is ½ pint of beer \[285 mL\], 1 glass of spirits \[25 mL\] or 1 glass of wine \[125 mL\])
* Prior or planned liver transplantation
* Presence of alternative causes of chronic liver disease, including alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, autoimmune hepatitis
* History of cirrhosis and/or hepatic impairment (Child-Pugh classes A, B and C) and/or hepatic decompensation including ascites, encephalopathy or variceal bleeding. Participants who show evidence of significant worsening of hepatic function will be excluded
* Participants with fibrosis evidence of cirrhosis, as determined by local transient elastography (TE, e.g., Fibroscan) values of ≥ 13.0 kPa, taken within the last 6 months. If TE has not been conducted within the 6 months prior to screening, then one will be conducted during the screening period and can be used as the Baseline value.
* Moderate to Severe active IBD or flare in colitis activity within the last 90 days requiring intensification of therapy beyond Baseline treatment. Participants with stable mild to moderate IBD, who are on treatment, are allowed provided they are stable for 3 months with 5-amino salicylic acid drugs or Azathioprine (allowed dose of azathioprine is 50-200 mg/day)
* Use of oral prednisolone \> 10 mg/day, biologics and/or hospitalization for colitis within 90 days are disallowed
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT); above the allowed cut-offs, as determined by Screening values:

  * AST \> 200 IU/L males and females
  * ALT: males \> 250 IU/L and females \> 200 IU/L
* Total Bilirubin and Direct Bilirubin; above the allowed cut-offs, as determined by Screening values:

  * Total Bilirubin \> 2.0 mg/dL
  * Direct Bilirubin \> 0.8 mg/dL
* International normalized ratio \> 1.3 in the absence of anticoagulants
* Immunoglobulin G4 (IgG4) \> 4 × ULN at Screening or evidence of IgG4-related sclerosing cholangitis
* Females who are pregnant or breastfeeding
* Any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the participant unsuitable for the study or unable to comply with the dosing and protocol requirements

Primary outcomes:
measure: Percentage Change From Baseline Through Week 24 in Serum Alkaline Phosphatase (ALP)
timeFrame: Baseline (Day 1) to Week 24
Secondary outcomes:
measure: Percentage of Participants Who Normalized ALP at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved Serum ALP of Less Than 1.5 Times Upper Limit of Normal (ULN) in Serum ALP at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Achieved a 50% Decrease in ALP at Week 24
timeFrame: Week 24
measure: Percentage of Participants With a Treatment-emergent Adverse Event (TEAE)
timeFrame: Baseline (Day 1) to Week 24
measure: Percentage of Participants Who Discontinued Due to a TEAE
timeFrame: Baseline (Day 1) to Week 24
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Sacramento
country: United States
facility: University of California, Davis Medical Center
state: California
city: San Francisco
country: United States
facility: Sutter Health, California Pacific Medical Center
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: New York
country: United States
facility: Icahn School of Medicine
state: New York
city: Calgary
country: Canada
facility: University of Calgary, Liver Unit
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta, Zeidler Ledcor Centre
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Toronto University Health Center
state: Ontario
Study officials:
affiliation: Allergan
name: J.P. Nicandro
role: STUDY_DIRECTOR
References:
citation: Eksteen B, Bowlus CL, Montano-Loza AJ, Lefebvre E, Fischer L, Vig P, Martins EB, Ahmad J, Yimam KK, Pockros PJ, Feld JJ, Minuk G, Levy C. Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study. Hepatol Commun. 2020 Dec 22;5(3):478-490. doi: 10.1002/hep4.1619. eCollection 2021 Mar.