Safety and Tolerability of Cilofexor in Participants With Primary Sclerosing Cholangitis (PSC) and Compensated Cirrhosis

NCT04060147 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: GS-US-428-5443
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Primary Sclerosing Cholangitis; Compensated Cirrhosis

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  First dose date up to 12 weeks plus 30 days

Study Arms (1)

Cilofexor

EXPERIMENTAL

Participants will receive escalating doses of cilofexor 30 mg, 60 mg, and 100 mg.

Drug: Cilofexor

Interventions

Cilofexor DRUG

Tablets administered orally once daily

Also known as: CILO, GS-9674

Cilofexor

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• Current moderate to severely active inflammatory bowel disease (IBD) (including ulcerative colitis, Crohn's disease, and indeterminate colitis).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (16)

Arizona Liver Health

Chandler, Arizona, 85224, United States

Location

California Liver Research Institute

Pasadena, California, 91105, United States

Location

University of California San Francisco, Liver Clinic

San Francisco, California, 94143, United States

Location

Schiff Center for Liver Diseases/University of Miami

Miami, Florida, 33136, United States

Location

Piedmont Atlanta Hospital

Atlanta, Georgia, 30309, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Louisiana Research Center, LLC

Shreveport, Louisiana, 71105, United States

Location

Minnesota Gastroenterology, PA

Maplewood, Minnesota, 55117, United States

Location

Northwell Health Center for Liver Diseases and Transplantation

Manhasset, New York, 11030, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, 75203, United States

Location

University of Virginia Medical Center

Charlottesville, Virginia, 22908, United States

Location

Bon Secours Richmond Community Hospital, Inc. d/b/a Bon Secours Liver Institute of Richmond

Richmond, Virginia, 23226, United States

Location

VCU Clinical Research Services Unit (CRSU) [Patient Site Address]

Richmond, Virginia, 23298, United States

Location

University of Washington at Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Liver Institute Northwest

Seattle, Washington, 98105, United States

Location

Related Publications (1)

• 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.

  PMID: 38976363 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

cilofexor

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2019
• First Posted: August 16, 2019
• Study Start: October 17, 2019
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: July 27, 2023
• Results First Posted: July 27, 2023

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)