Primary Sclerosing CholangitisPhase 1NCT04060147
Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
A Phase 1 study testing Cilofexor in people with Primary Sclerosing Cholangitis and Compensated Cirrhosis, run by Gilead Sciences at 16 sites in United States.
Trial summary
The primary objective of this study is to assess the safety and tolerability of escalating doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and compensated cirrhosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Sclerosing Cholangitis, Compensated Cirrhosis
- What is being tested?
- Cilofexor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 16 sitesUnited States
- Study dates
- 17 Oct 2019to 2 Sep 2021
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC]) or liver biopsy
- Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal imaging [magnetic resonance imaging (MRI), computed tomography (CT), or Ultrasound], or a screening FibroScan®, enhanced liver fibrosis (ELF)™, or FibroTest®.
- Individual has the following laboratory parameters at the Screening visit, as determined by the central laboratory:
- Estimated glomerular filtration rate (eGFR) > 60 milliliter/minute (mL/min), as calculated by the Cockcroft-Gault equation
- Alanine aminotransferase (ALT) ≤ 5 x upper limit of the normal (ULN)
- Total 2 milligram/deciliter (mg/dL), unless the individual is known to have Gilbert's syndrome or hemolytic anemia
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- International normalized ratio (INR) ≤ 1.4, unless due to therapeutic anticoagulation
- Platelet count ≥ 75,000/microliter (μL). Individuals with evidence of high-risk esophageal or gastric varices in the opinion of the investigator are excluded
- Negative anti-mitochondrial antibody
Who cannot join
- Current or prior history of any of the following
- Decompensated liver disease, including ascites, hepatic encephalopathy (HE), or variceal hemorrhage
- Liver transplantation
- Cholangiocarcinoma or hepatocellular carcinoma (HCC).
- Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
- Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
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- Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis).
- Note: Individuals with IBD who currently have an external ostomy bag and/or proctocolectomy are not subject to this exclusion criterion and need not undergo IBD Symptom Severity Assessment.
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Piedmont Atlanta Hospital
Atlanta, Georgia, 30309
Arizona Liver Health
Chandler, Arizona, 85224
University of Virginia Medical Center
Charlottesville, Virginia, 22908
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
Indiana University Health University Hospital
Indianapolis, Indiana, 46202
Northwell Health Center for Liver Diseases and Transplantation
Manhasset, New York, 11030
Minnesota Gastroenterology, PA
Maplewood, Minnesota, 55117
Schiff Center for Liver Diseases/University of Miami
Miami, Florida, 33136
California Liver Research Institute
Pasadena, California, 91105
Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond
Richmond, Virginia, 23226
VCU Clinical Research Services Unit (CRSU) [Patient Site Address]
Richmond, Virginia, 23298
University of Rochester Medical Center
Rochester, New York, 14642
University of California San Francisco, Liver Clinic
San Francisco, California, 94143
University of Washington at Harborview Medical Center
Seattle, Washington, 98104
Liver Institute Northwest
Seattle, Washington, 98105
Louisiana Research Center, LLC
Shreveport, Louisiana, 71105
About this study
Official title: A Proof-of-Concept, Open-Label Study Evaluating the Safety and Tolerability of Cilofexor in Subjects With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
The primary objective of this study is to assess the safety and tolerability of escalating doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and compensated cirrhosis.
- Being tested
- 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 CILO, GS-9674
Tablets administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Cilofexor | Experimental | Participants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg. Receives: Drug: Cilofexor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Treatment-emergent adverse events (TEAEs) were either defined any 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 or any AEs leading to premature discontinuation of study drug.
Measured: First dose date up to 12 weeks plus 30 days
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs.
Measured: First dose date up to 12 weeks plus 30 days
Percentage of Participants Who Experienced Laboratory Abnormalities
Treatment-emergent laboratory abnormalities are 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 plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
Measured: First dose date up to 12 weeks plus 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2019
- Study start17 Oct 2019
- Primary completion2 Sep 2021
- Study completion2 Sep 2021
Why it stopped: The study enrollment was terminated early by the sponsor due to recruitment challenges.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT04060147
- Sponsor's protocol ID
- GS-US-428-5443
- Status last verified
- Aug 2022
- First submitted
- 15 Aug 2019
- Last updated
- 27 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Levy C, Caldwell S, Mantry P, Luketic V, Landis CS, Huang J, Mena E, Maheshwari R, Rank K, Xu J, Malkov VA, Billin AN, Liu X, Lu X, Barchuk WT, Watkins TR, Chung C, Myers RP, Kowdley KV. Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study. Clin Transl Gastroenterol. 2024 Aug 1;15(8):e00744. doi: 10.14309/ctg.0000000000000744.
PubMed 38976363
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept, Open-Label Study Evaluating the Safety and Tolerability of Cilofexor in Subjects With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis
- ClinicalTrials.gov ID
- NCT04060147
- Acronym / sponsor ID
- GS-US-428-5443
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study enrollment was terminated early by the sponsor due to recruitment challenges.
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- 17 Oct 2019 (actual)
- Primary completion
- 2 Sep 2021 (actual)
- Study completion
- 2 Sep 2021 (actual)
- First posted
- 16 Aug 2019 (actual)
- Results
- Posted 27 Jul 2023
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 assess the safety and tolerability of escalating doses of cilofexor (CILO) in participants with primary sclerosing cholangitis (PSC) and compensated cirrhosis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cilofexor | Experimental | Drug: CilofexorParticipants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Diagnosis PSC based on cholangiogram (magnetic resonance cholangiopancreatography [MRCP], endoscopic retrograde cholangiopancreatography [ERCP], or percutaneous transhepatic cholangiogram [PTC]) or liver biopsy
- Individuals have evidence of cirrhosis based on historical liver biopsy, abdominal imaging [magnetic resonance imaging (MRI), computed tomography (CT), or Ultrasound], or a screening FibroScan®, enhanced liver fibrosis (ELF)™, or FibroTest®.
- Individual has the following laboratory parameters at the Screening visit, as determined by the central laboratory:
Key exclusion criteria (9 listed)
- Current or prior history of any of the following
- Model for End-stage Liver Disease (MELD) score > 12 at Screening, unless due to an alternate etiology such as therapeutic anticoagulation
- Child-Pugh (CP) score > 6 at Screening, unless due to an alternative etiology such as Gilbert's syndrome or therapeutic anticoagulation
- Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis).
- Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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: CILO, GS-9674Tablets administered orally once daily | Drug | Cilofexor |
Primary outcome
Percentage of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time frame: First dose date up to 12 weeks plus 30 days
Treatment-emergent adverse events (TEAEs) were either defined any 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 or any AEs leading to premature discontinuation of study drug.
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (SAEs)
Time frame: First dose date up to 12 weeks plus 30 days
A treatment emergent SAE was defined as an event that, at any dose, resulted in the following: death ; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; a congenital anomaly/birth defect; a medically important event or reaction: such events may not be immediately life-threatening or result in death or hospitalization but may jeopardize the subject or may require intervention to prevent one of the other outcomes constituting SAEs.
Percentage of Participants Who Experienced Laboratory Abnormalities
Time frame: First dose date up to 12 weeks plus 30 days
Treatment-emergent laboratory abnormalities are 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 plus 30 days. Grade 1: mild; Grade 2: moderate; Grade 3: severe; Grade 4: life-threatening.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38976363Levy C, Caldwell S, Mantry P, Luketic V, Landis CS, Huang J, Mena E, Maheshwari R, Rank K, Xu J, Malkov VA, Billin AN, Liu X, Lu X, Barchuk WT, Watkins TR, Chung C, Myers RP, Kowdley KV. Cilofexor in Patients With Compensated Cirrhosis Due to Primary Sclerosing Cholangitis: An Open-Label Phase 1B Study. Clin Transl Gastroenterol. 2024 Aug 1;15(8):e00744. doi: 10.14309/ctg.0000000000000744.
- 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
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cilofexor in people with Primary Sclerosing Cholangitis and Compensated Cirrhosis, run by Gilead Sciences at 16 sites in United States.
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 9 inclusion and 9 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: stopped early, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 27 Jul 2023). 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 Who Experienced Treatment-emergent Adverse Events (TEAEs) (time frame: First dose date up to 12 weeks plus 30 days). 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 NCT04060147, 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 27 Jul 2023.