Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Cilofexor · 3 trials · 3 indications
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.
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.
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).
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
AUCinf is defined as the concentration of drug extrapolated to infinite time.
Cmax is defined as the maximum concentration of drug.
%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
Clast is defined as the last observable concentration of drug.
Tmax is defined as the time (observed time point) of Cmax.
Tlast is defined as the time (observed time point) of Clast.
λz is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.
CL/F is defined as the apparent oral clearance following administration of the drug.
Vz/F is defined as the apparent volume of distribution of the drug.
t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
AUClast is defined as the concentration of drug from time zero to the last quantifiable concentration.
AUCinf is defined as the concentration of drug extrapolated to infinite time (area under the plasma concentration versus time curve extrapolated to infinite time).
Cmax is defined as the maximum observed concentration of drug in plasma.
AUCtau is the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval).
Cmax is defined as the maximum observed concentration of drug in plasma.
Ctau is defined as the observed drug concentration at the end of the dosing interval.
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product, which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Investigator determined the ECG findings were clinically significant.
Treatment-emergent laboratory (Hematology, Chemistry, and Urinalysis) abnormalities were defined as values that increase at least one toxicity grade from baseline. Laboratory Abnormalities are graded by the investigator as Grade 1, 2, 3, or 4 according to the modified Gilead Sciences, Inc (GSI) Grading Scale. The most severe graded abnormality from all tests was counted for each participant. Data is only reported for those Grades reported in 1 or more participants.
| Arm | Type | Description |
|---|---|---|
| Cilofexor 100 mg (Blinded Study Phase) | EXPERIMENTAL | Cilofexor 100 mg + placebo to match cilofexor 30 mg for up to 12.6 weeks |
| Cilofexor 30 mg (Blinded Study Phase) | EXPERIMENTAL | Cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.7 weeks |
| Placebo (Blinded Study Phase) | PLACEBO_COMPARATOR | Placebo to match cilofexor 30 mg + placebo to match cilofexor 100 mg for up to 12.3 weeks |
| Cilofexor (Open Label Extension Phase) | EXPERIMENTAL | Following the Blinded Study Phase, eligible participants received cilofexor for an additional up to 97.4 weeks. |
| Cohort 1: Mild Hepatic Impairment | EXPERIMENTAL | Participants with mild hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
| Cohort 1: Normal Hepatic Function | EXPERIMENTAL | Matched normal hepatic function participants to mild hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
| Cohort 2: Moderate Hepatic Impairment | EXPERIMENTAL | Participants with moderate hepatic impairment will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
| Cohort 2: Normal Hepatic Function | EXPERIMENTAL | Matched normal hepatic function participants to moderate hepatic impairment participants will receive a single oral dose of cilofexor 30 mg (3 x 10 mg tablets). |
| Cohort 3: Severe Hepatic Impairment | EXPERIMENTAL | Participants with severe hepatic impairment will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). |
| Cohort 3: Normal Hepatic Function | EXPERIMENTAL | Matched normal hepatic function participants to severe hepatic impairment participants will receive a single oral dose of cilofexor 10 mg (1 x 10 mg tablet). |
| Cohort 1: Cilofexor 10 mg | EXPERIMENTAL | Participants in fasted state will receive cilofexor 10 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg or placebo once daily from Day 7 to Day 20. |
| Cohort 2: Cilofexor 30 mg | EXPERIMENTAL | Participants in fasted state will receive cilofexor 30 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 30 mg or placebo once daily from Day 7 to Day 20. |
| Cohort 3: Cilofexor 100 mg | EXPERIMENTAL | Participants in fasted state will receive cilofexor 100 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg or placebo once daily from Day 7 to Day 20. |
| Cohort 4: Cilofexor 300 mg | EXPERIMENTAL | Participants in fasted state will receive cilofexor 300 mg or placebo once on Day 1 followed by a 5-day washout period then receive cilofexor 300 mg or placebo once daily from Day 7 to Day 20. |
| Cohort 5: Cilofexor 100 mg | EXPERIMENTAL | Participants in fed state will receive cilofexor 100 mg or placebo once with food on Day 1 followed by a 5-day washout period then receive cilofexor 100 mg or placebo tablet, orally, once daily with food from Day 7 to Day 20. |
| Cohort 6: Cilofexor 50 mg | EXPERIMENTAL | Participants in fed state will receive cilofexor 50 mg or placebo twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 50 mg or placebo twice daily from Day 7 to Day 20. |
| Cohort 7: Cilofexor 15 mg | EXPERIMENTAL | Participants in fed state will receive cilofexor 15 mg or placebo twice with food on Day 1 followed by a 5-day washout period then receive cilofexor 15 mg or placebo twice daily from Day 7 to Day 20. |
| Cohort 8: Cilofexor 10 mg | EXPERIMENTAL | Participants in fed state will receive cilofexor 10 mg or placebo once with food on Day 1 followed by a 5-day washout period then receive cilofexor 10 mg or placebo once daily from Day 7 to Day 20. |
| Cohort 9: Cilofexor | EXPERIMENTAL | Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. |
| Cohort 10: Cilofexor | EXPERIMENTAL | Participants will receive cilofexor up to 300 mg or placebo once daily in the evening on empty stomach. |
| Name | Type | Description |
|---|---|---|
| Cilofexor | DRUG | Tablet(s) administered orally once daily with food |
| Placebo to match cilofexor | DRUG | Tablet(s) administered orally once daily with food |
| Placebo | DRUG | Tablets administered orally |
Key Inclusion Criteria: * 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 ...
Cilofexor is an investigational small molecule being developed for Nonalcoholic Steatohepatitis (NASH) and Primary Sclerosing Cholangitis (PSC). It is currently in clinical development and has not been approved by the FDA.
Cilofexor is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on the NASDAQ under the ticker symbol GILD.
Cilofexor is in Phase 1 clinical development. It has completed two Phase 1 trials and one Phase 2 trial, but it remains investigational and is not yet approved for any indication.
Cilofexor has completed two Phase 1 trials: NCT02654002, a healthy volunteer study in the United States, and NCT02808312, a hepatic impairment study in the United States and New Zealand. A Phase 2 trial, NCT02943460, evaluated Cilofexor in adults with Primary Sclerosing Cholangitis without cirrhosis.
Cilofexor is a small molecule that targets the farnesoid X receptor (FXR), a nuclear receptor involved in bile acid metabolism and inflammatory pathways. By modulating FXR activity, it aims to address the underlying mechanisms of NASH and PSC.