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

NCT02653625 | Completed Phase 2 Results

• 1 other identifier: 652-205
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 9

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.

Conditions

Primary Sclerosing Cholangitis

Keywords

Primary Sclerosing Cholangitis

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Day 1) to Week 24

Secondary Outcomes (5)

• Percentage of Participants Who Normalized ALP at Week 24

  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

  Week 24

• Percentage of Participants Who Achieved a 50% Decrease in ALP at Week 24

  Week 24

• Percentage of Participants With a Treatment-emergent Adverse Event (TEAE)

  Baseline (Day 1) to Week 24

• Percentage of Participants Who Discontinued Due to a TEAE

  Baseline (Day 1) to Week 24

Study Arms (1)

Cenicriviroc 150 mg

EXPERIMENTAL

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

Drug: Cenicriviroc 150 mg

Interventions

Cenicriviroc 150 mg DRUG

One tablet of CVC 150 mg once daily taken with food in the morning.

Also known as: CVC 150 mg

Cenicriviroc 150 mg

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tobira Therapeutics, Inc.: lead

Study Sites (9)

Scripps Clinic

La Jolla, California, 92037, United States

Location

University of California, Davis Medical Center

Sacramento, California, 95817, United States

Location

Sutter Health, California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Icahn School of Medicine

New York, New York, 10029, United States

Location

University of Calgary, Liver Unit

Calgary, Alberta, T2N 4Z6, Canada

Location

University of Alberta, Zeidler Ledcor Centre

Edmonton, Alberta, T6G 2X8, Canada

Location

University of Manitoba

Winnipeg, Manitoba, R3E 3P4, Canada

Location

Toronto University Health Center

Toronto, Ontario, M5G 2C4, Canada

Location

Related Publications (1)

• 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.

  PMID: 33681680 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

cenicriviroc

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• J.P. Nicandro

  Allergan

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 12, 2016
• Study Start: March 14, 2016
• Primary Completion: August 31, 2017
• Study Completion: August 31, 2017
• Last Updated: October 1, 2018
• Results First Posted: October 1, 2018

Record last verified: 2018-08

Locations

US (5); CA (4)