Primary Sclerosing CholangitisPhase 2NCT02653625
PERSEUS: Preliminary Efficacy and Safety of Cenicriviroc in Adult Participants With Primary Sclerosing Cholangitis
A Phase 2 study testing Cenicriviroc 150 mg in people with Primary Sclerosing Cholangitis, run by Tobira Therapeutics, Inc. at 9 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Sclerosing Cholangitis
- What is being tested?
- Cenicriviroc 150 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 14 Mar 2016to 31 Aug 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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])
Show all 22Show fewer
- 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
Trial locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States5 sites
Scripps Clinic
La Jolla, California, 92037
University of Miami
Miami, Florida, 33136
Icahn School of Medicine
New York, New York, 10029
University of California, Davis Medical Center
Sacramento, California, 95817
Sutter Health, California Pacific Medical Center
San Francisco, California, 94115
Canada4 sites
University of Calgary, Liver Unit
Calgary, Alberta, T2N 4Z6
University of Alberta, Zeidler Ledcor Centre
Edmonton, Alberta, T6G 2X8
Toronto University Health Center
Toronto, Ontario, M5G 2C4
University of Manitoba
Winnipeg, Manitoba, R3E 3P4
About this study
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)
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
- Being tested
- Cenicriviroc 150 mg
- Keywords
- Primary Sclerosing Cholangitis
- Medical subject headings
- Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cenicriviroc 150 mgDrug
Also called CVC 150 mg
One tablet of CVC 150 mg once daily taken with food in the morning.
| Study group | Role | What they receive |
|---|---|---|
| Cenicriviroc 150 mg | Experimental | One tablet of Cenicriviroc 150 mg once daily with food in the morning for 24 weeks. Receives: Drug: Cenicriviroc 150 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Day 1) to Week 24
Secondary outcomes (5)
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.
Measured: 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.
Measured: Week 24
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.
Measured: Week 24
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.
Measured: Baseline (Day 1) to Week 24
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.
Measured: Baseline (Day 1) to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2016 (estimated)
- Study start14 Mar 2016
- Primary completion31 Aug 2017
- Study completion31 Aug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary Sclerosing CholangitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tobira Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- J.P. Nicandro, Study director, Allergan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02653625
- Sponsor's protocol ID
- 652-205
- Status last verified
- Aug 2018
- First submitted
- 8 Jan 2016
- Last updated
- 1 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 33681680
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02653625
- Acronym / sponsor ID
- 652-205
- Conditions
- Primary Sclerosing Cholangitis
- Keywords
- Primary Sclerosing Cholangitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Tobira Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Mar 2016 (actual)
- Primary completion
- 31 Aug 2017 (actual)
- Study completion
- 31 Aug 2017 (actual)
- First posted
- 12 Jan 2016 (estimated)
- Results
- Posted 1 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cenicriviroc 150 mg | Experimental | Drug: Cenicriviroc 150 mgOne tablet of Cenicriviroc 150 mg once daily with food in the morning for 24 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cenicriviroc 150 mgAlso: CVC 150 mgOne tablet of CVC 150 mg once daily taken with food in the morning. | Drug | Cenicriviroc 150 mg |
Primary outcome
Percentage Change From Baseline Through Week 24 in Serum Alkaline Phosphatase (ALP)
Time frame: Baseline (Day 1) to Week 24
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.
5 secondary outcomes
Percentage of Participants Who Normalized ALP at Week 24
Time frame: 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
Time frame: Week 24
Percentage of Participants Who Achieved a 50% Decrease in ALP at Week 24
Time frame: Week 24
Percentage of Participants With a Treatment-emergent Adverse Event (TEAE)
Time frame: Baseline (Day 1) to Week 24
Percentage of Participants Who Discontinued Due to a TEAE
Time frame: Baseline (Day 1) to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33681680Eksteen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
J.P. Nicandro study director
Allergan
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cenicriviroc 150 mg in people with Primary Sclerosing Cholangitis, run by Tobira Therapeutics, Inc. at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change From Baseline Through Week 24 in Serum Alkaline Phosphatase (ALP) (time frame: Baseline (Day 1) to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02653625, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2018.