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PERSEUS: Preliminary Efficacy and Safety of Cenicriviroc in Adult Participants With Primary Sclerosing Cholangitis

Primary Purpose

Primary Sclerosing Cholangitis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Cenicriviroc 150 mg
Sponsored by
Tobira Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring Primary Sclerosing Cholangitis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Scripps Clinic
  • University of California, Davis Medical Center
  • Sutter Health, California Pacific Medical Center
  • University of Miami
  • Icahn School of Medicine
  • University of Calgary, Liver Unit
  • University of Alberta, Zeidler Ledcor Centre
  • University of Manitoba
  • Toronto University Health Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cenicriviroc 150 mg

Arm Description

One tablet of Cenicriviroc 150 mg once daily with food in the morning for 24 weeks.

Outcomes

Primary Outcome Measures

Percentage Change From Baseline Through Week 24 in Serum Alkaline Phosphatase (ALP)
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. The percent change from Baseline was defined as 100*(value at each visit - Baseline value)/Baseline value. The Baseline value was defined as the last non-missing value on or before the Baseline visit (Day 1). A negative percentage change from baseline indicates an improvement.

Secondary Outcome Measures

Percentage of Participants Who Normalized ALP at Week 24
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. Normalization was defined as ALP values outside of the central laboratory reference range at baseline, but within the central laboratory reference range at Week 24.
Percentage of Participants Who Achieved Serum ALP of Less Than 1.5 Times Upper Limit of Normal (ULN) in Serum ALP at Week 24
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. The upper limit of normal ALP was defined according to the central laboratory reference ranges.
Percentage of Participants Who Achieved a 50% Decrease in ALP at Week 24
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease.
Percentage of Participants With a Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of whether related to the medicinal (investigational) product. A TEAE was defined as an AE with an onset that occurred after receiving treatment.
Percentage of Participants Who Discontinued Due to a TEAE
An adverse event was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of whether related to the medicinal (investigational) product. A TEAE was defined as an AE with an onset that occurred after receiving treatment.

Full Information

First Posted
January 8, 2016
Last Updated
August 31, 2018
Sponsor
Tobira Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02653625
Brief Title
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

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
March 14, 2016 (Actual)
Primary Completion Date
August 31, 2017 (Actual)
Study Completion Date
August 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tobira Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
Primary Sclerosing Cholangitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cenicriviroc 150 mg
Arm Type
Experimental
Arm Description
One tablet of Cenicriviroc 150 mg once daily with food in the morning for 24 weeks.
Intervention Type
Drug
Intervention Name(s)
Cenicriviroc 150 mg
Other Intervention Name(s)
CVC 150 mg
Intervention Description
One tablet of CVC 150 mg once daily taken with food in the morning.
Primary Outcome Measure Information:
Title
Percentage Change From Baseline Through Week 24 in Serum Alkaline Phosphatase (ALP)
Description
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. The percent change from Baseline was defined as 100*(value at each visit - Baseline value)/Baseline value. The Baseline value was defined as the last non-missing value on or before the Baseline visit (Day 1). A negative percentage change from baseline indicates an improvement.
Time Frame
Baseline (Day 1) to Week 24
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Normalized ALP at Week 24
Description
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. Normalization was defined as ALP values outside of the central laboratory reference range at baseline, but within the central laboratory reference range at Week 24.
Time Frame
Week 24
Title
Percentage of Participants Who Achieved Serum ALP of Less Than 1.5 Times Upper Limit of Normal (ULN) in Serum ALP at Week 24
Description
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease. The upper limit of normal ALP was defined according to the central laboratory reference ranges.
Time Frame
Week 24
Title
Percentage of Participants Who Achieved a 50% Decrease in ALP at Week 24
Description
ALP was used as a primary surrogate marker for measuring Primary Sclerosing Cholangitis disease.
Time Frame
Week 24
Title
Percentage of Participants With a Treatment-emergent Adverse Event (TEAE)
Description
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of whether related to the medicinal (investigational) product. A TEAE was defined as an AE with an onset that occurred after receiving treatment.
Time Frame
Baseline (Day 1) to Week 24
Title
Percentage of Participants Who Discontinued Due to a TEAE
Description
An adverse event was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, regardless of whether related to the medicinal (investigational) product. A TEAE was defined as an AE with an onset that occurred after receiving treatment.
Time Frame
Baseline (Day 1) to Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
J.P. Nicandro
Organizational Affiliation
Allergan
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California, Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Sutter Health, California Pacific Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Icahn School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Calgary, Liver Unit
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4Z6
Country
Canada
Facility Name
University of Alberta, Zeidler Ledcor Centre
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2X8
Country
Canada
Facility Name
University of Manitoba
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 3P4
Country
Canada
Facility Name
Toronto University Health Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
33681680
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.
Results Reference
derived

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PERSEUS: Preliminary Efficacy and Safety of Cenicriviroc in Adult Participants With Primary Sclerosing Cholangitis

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