Primary Sclerosing CholangitisPhase 2NCT02943460
Study to Evaluate the Safety, Tolerability, and Efficacy of Cilofexor in Adults With Primary Sclerosing Cholangitis Without Cirrhosis
A Phase 2 study testing Cilofexor in people with Primary Sclerosing Cholangitis, run by Gilead Sciences at 23 sites in 4 countries.
Trial summary
The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Primary Sclerosing Cholangitis
- What is being tested?
- Cilofexor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 23 sitesin 4 countries
- Study dates
- 29 Nov 2016to 18 May 2020
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiogram (PTC)) within the previous 12 months
- Serum alkaline phosphatase (ALP) > 1.67 x upper limit of the normal range (ULN)
- For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For individuals not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment
- For individuals being administered biologic treatments (eg, antitumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial
- Screening FibroSURE/FibroTest® <0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of total bilirubin.
Who cannot join
- Alanine aminotransferase (ALT) > 10 x ULN
- Total bilirubin > 2 x ULN
- International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
- Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)
- Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Individuals with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy;
- Ascending cholangitis within 60 days of screening
Show all 14Show fewer
- Presence of a percutaneous drain or bile duct stent
- Use of fibrates or obeticholic acid within 3 months prior to screening through the end of treatment
- Cirrhosis of the liver as defined by any of the following:
- Historical liver biopsy demonstrating cirrhosis (eg, Ludwig stage 4 or Ishak stage ≥ 5)
- Prior history of decompensated liver disease, including ascites, hepatic encephalopathy or variceal bleeding
- Liver stiffness > 14.4 kilopascal (kPa) by FibroScan
- Current, active inflammatory bowel disease (IBD) defined as a partial Mayo score of > 1 and/or a score on the Rectal Bleeding domain > 0.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
23 sites in 4 countries.
23 sites in 4 countries
United States16 sites
University of Colorado Denver
Aurora, Colorado, 80045
University of Virginia
Charlottesville, Virginia, 22908
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
Duke University Medical Center
Durham, North Carolina, 27710
Indiana University Health University Hospital
Indianapolis, Indiana, 46202
Florida Digestive Health Specialists
Lakewood Rch, Florida, 34211
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, 33136
Intermountain Medical Center - Transplant Services
Murray, Utah, 84107
Bon Secours St. Mary's Hospital of Richmond, Inc.
Richmond, Virginia, 23226
McGuire VA Medical Center
Richmond, Virginia, 23249
Virginia Commonwealth University
Richmond, Virginia, 23298
University of California, Davis Medical Center
Sacramento, California, 95817
Minnesota Gastroenterology, P.A.
Saint Paul, Minnesota, 55117
University of California San Francisco
San Francisco, California, 94143
Swedish Organ Transplant and Liver Center
Seattle, Washington, 98104
University of Washington
Seattle, Washington, 98104
United Kingdom4 sites
New Queen Elizabeth Hospital NHS Foundation Trust
Birmingham
Royal Free Hospital
London, NW3 2QG
King's College Hospital NHS Foundation Trust
London, SE5 9RS
Norfolk and Norwich University Hospital
Norwich, NR4 7UY
Canada2 sites
University of Calgary Liver Unit (Heritage Medical Research Clinic)
Calgary, Alberta
Toronto Liver Centre
Toronto, Ontario, M6H 3M1
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Sclerosing Cholangitis Without Cirrhosis
The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC).
- Conditions
- Primary Sclerosing Cholangitis
- Being tested
- Cilofexor, Placebo to match cilofexor
- Medical subject headings
- Cholangitis, Sclerosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CilofexorDrug
Also called GS-9674
Tablet(s) administered orally once daily with food
Placebo to match cilofexorDrug
Tablet(s) administered orally once daily with food
| Study group | Role | What they receive |
|---|---|---|
| Cilofexor 100 mg (Blinded Study Phase) | Experimental | Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks Receives: Drug: Cilofexor; Drug: Placebo to match cilofexor |
| Cilofexor 30 mg (Blinded Study Phase) | Experimental | Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks Receives: Drug: Cilofexor; Drug: Placebo to match cilofexor |
| Placebo (Blinded Study Phase) | Placebo comparator | Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks Receives: Drug: Placebo to match cilofexor |
| Cilofexor (Open Label Extension Phase) | Experimental | Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks. Receives: Drug: Cilofexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.
Measured: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
Measured: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug in the Blinded Phase plus 30 days (and prior to or on the first dose date of the OLE phase). The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).
Measured: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study start29 Nov 2016
- Primary completion28 Feb 2018
- Study completion18 May 2020
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.
- More trials run by Gilead SciencesThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gilead Study Director, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02943460
- Sponsor's protocol ID
- GS-US-428-4025
- Other IDs
- 2016-002442-23, 2016
- Status last verified
- May 2021
- First submitted
- 13 Jun 2016
- Last updated
- 7 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, Eksteen B, Agarwal K, Muir A, Rushbrook S, Lu X, Xu J, Chuang JC, Billin AN, Li G, Chung C, Subramanian GM, Myers RP, Bowlus CL, Kowdley KV. The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801. doi: 10.1002/hep.30509. Epub 2019 Mar 10.
PubMed 30661255
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety, Tolerability, and Efficacy of GS-9674 in Subjects With Primary Sclerosing Cholangitis Without Cirrhosis
- ClinicalTrials.gov ID
- NCT02943460
- Acronym / sponsor ID
- GS-US-428-4025
- Conditions
- Primary Sclerosing Cholangitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2016 (actual)
- Primary completion
- 28 Feb 2018 (actual)
- Study completion
- 18 May 2020 (actual)
- First posted
- 24 Oct 2016 (estimated)
- Results
- Posted 12 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety and tolerability of cilofexor in adults with primary sclerosing cholangitis (PSC).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cilofexor 100 mg (Blinded Study Phase) | Experimental | Drug: Cilofexor, Drug: Placebo to match cilofexorCilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks |
| Cilofexor 30 mg (Blinded Study Phase) | Experimental | Drug: Cilofexor, Drug: Placebo to match cilofexorCilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks |
| Placebo (Blinded Study Phase) | Placebo comparator | Drug: Placebo to match cilofexorPlacebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks |
| Cilofexor (Open Label Extension Phase) | Experimental | Drug: CilofexorFollowing the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of PSC based on cholangiogram (magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or percutaneous transhepatic cholangiogram (PTC)) within the previous 12 months
- Serum alkaline phosphatase (ALP) > 1.67 x upper limit of the normal range (ULN)
- For individuals on ursodeoxycholic acid (UDCA), the dose of UDCA must have been stable for at least 12 months prior to screening through the end of treatment. For individuals not on UDCA, no UDCA use for at least 12 months before screening through the end of treatment
- For individuals being administered biologic treatments (eg, antitumor necrosis factor (TNF) or anti-integrin monoclonal antibodies), immunosuppressants or systemic corticosteroids, the dose must have been stable at least 3 months prior to screening and anticipated to remain stable throughout the trial
- Screening FibroSURE/FibroTest® <0.75 unless a historical liver biopsy within 12 months of screening does not reveal cirrhosis. In adults with Gilbert's syndrome or hemolysis, FibroSURE/FibroTest® will be calculated using direct bilirubin instead of total bilirubin.
Key exclusion criteria (14 listed)
- Alanine aminotransferase (ALT) > 10 x ULN
- Total bilirubin > 2 x ULN
- International normalized ratio (INR) > 1.2 unless on anticoagulant therapy
- Small-duct PSC (histologic evidence of PSC with normal bile ducts on cholangiography)
- Other causes of liver disease including secondary sclerosing cholangitis and viral, metabolic, alcoholic, and other autoimmune conditions. Individuals with hepatic steatosis may be included if there is no evidence of nonalcoholic steatohepatitis (NASH) in the opinion of the investigator or on liver biopsy;
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 |
|---|---|---|
| CilofexorAlso: GS-9674Tablet(s) administered orally once daily with food | Drug | Cilofexor (Open Label Extension Phase), Cilofexor 100 mg (Blinded Study Phase), Cilofexor 30 mg (Blinded Study Phase) |
| Placebo to match cilofexorTablet(s) administered orally once daily with food | Drug | Cilofexor 100 mg (Blinded Study Phase), Cilofexor 30 mg (Blinded Study Phase), Placebo (Blinded Study Phase) |
Primary outcome
Percentage of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase
Time frame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Treatment-emergent adverse events occurring during the Blinded Phase were defined as 1 or both of the following: 1) Any adverse events (AEs) with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug in the Blinded Phase (and before the first dosing date in the Open Label Extension (OLE) Phase), or 2) Any AEs leading to premature discontinuation of study drug in the Blinded Phase.
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events During the Blinded Phase
Time frame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
A serious adverse event was defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities During the Blinded Phase
Time frame: First dose date up to last dose date plus 30 days (Up to 17 weeks)
Treatment-emergent laboratory abnormalities occurring during the Blinded Phase were defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug in the Blinded Phase plus 30 days (and prior to or on the first dose date of the OLE phase). The Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 was used for assigning toxicity grades (0 to 4, with higher grades indicating more severity).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 30661255Trauner M, Gulamhusein A, Hameed B, Caldwell S, Shiffman ML, Landis C, Eksteen B, Agarwal K, Muir A, Rushbrook S, Lu X, Xu J, Chuang JC, Billin AN, Li G, Chung C, Subramanian GM, Myers RP, Bowlus CL, Kowdley KV. The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis. Hepatology. 2019 Sep;70(3):788-801. doi: 10.1002/hep.30509. Epub 2019 Mar 10.
- Individual participant dataSharing planned: No
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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.
Gilead Study Director study director
Gilead Sciences
23 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cilofexor in people with Primary Sclerosing Cholangitis, run by Gilead Sciences at 23 sites in 4 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 5 inclusion and 14 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 7 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United States, United Kingdom, Canada, Austria. 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. Some participants in this study may receive a placebo. 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 12 Mar 2019). 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 of Participants Experiencing Treatment-Emergent Adverse Events During the Blinded Phase (time frame: First dose date up to last dose date plus 30 days (Up to 17 weeks)). The study lists 3 primary outcomes in all. 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 NCT02943460, 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 7 Jun 2021.