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Selonsertib

Phase 2

Alcoholic Hepatitis (AH) | Small molecule | Gastrointestinal |Gilead Sciences, Inc.|Last Updated: Jan 27, 2021

Success Probability

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLEDDMC
Total Trials1
Total Enrollment104

FDA Designations

No designations recorded

Clinical trial landscape

Selonsertib · 4 trials · 3 indications

Phase 2 3Phase 1 1
NCT02854631Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)Alcoholic Hepatitis (AH)
COMPLETED104 Analytics
NCT02234141Selonsertib in Adults With Pulmonary Arterial HypertensionPulmonary Arterial Hypertension
COMPLETED151 Analytics
NCT02177786Efficacy, Safety, and Tolerability of Selonsertib (GS-4997) in Participants With Diabetic Kidney DiseaseDiabetic Kidney Disease
COMPLETED334 Analytics
PHASE2COMPLETED
Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)
Alcoholic Hepatitis (AH)Unlock trial analytics
PHASE2COMPLETED
Selonsertib in Adults With Pulmonary Arterial Hypertension
Pulmonary Arterial HypertensionUnlock trial analytics
PHASE2COMPLETED
Efficacy, Safety, and Tolerability of Selonsertib (GS-4997) in Participants With Diabetic Kidney Disease
Diabetic Kidney DiseaseUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
Up to Day 28 plus 30 days

An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Laboratory toxicity grading was based on Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03.

Change From Baseline in Pulmonary Vascular Resistance (PVR) at Week 24, as Measured by Right Heart Catheterization (RHC)
Baseline to Week 24

PVR is a measure of the extent to which pulmonary circulation resists cardiac output. Change from Baseline was calculated as the value at Week 24 minus the value at Baseline. The Week 24 value was defined as the last assessment at or prior to Week 24.

Change in eGFR From Baseline at Week 48
Baseline; Week 48

The values of eGFR were calculated using the MDRD equation: eGFR = 175 x Serum Creatinine\^-1.154 × age\^-0.203 × 1.212 (if participant is black) × 0.742 (if female).

Pharmacokinetic (PK) Parameter: AUCinf of Selonsertib and Its Metabolite GS-607509
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

AUCinf is defined as the concentration of drug extrapolated to infinite time.

PK Parameter: AUClast of Selonsertib and Its Metabolite GS-607509
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

AUClast is defined as the concentration of drug from time zero to the last observable concentration.

PK Parameter: Cmax of Selonsertib and Its Metabolite GS-607509
0 (predose), 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours postdose on Day 1. Additional PK samples were collected at the Day 10 and 14 follow-up visits approximately the same time as the Day 1 predose sample.

Cmax is defined as the maximum concentration of drug.

Secondary Endpoints

Percentage of Participants Who Died by Day 28
Day 28
Percentage of Participants Who Died by Week 8
Week 8
Percentage of Participants Who Died by Week 12
Week 12
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Study Design & Arms

AllocationRANDOMIZED
MaskingDOUBLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Selonsertib + PrednisoloneEXPERIMENTALSelonsertib + prednisolone for 28 days
PrednisolonePLACEBO_COMPARATORSelonsertib placebo + prednisolone for 28 days
Selonsertib 2 mgEXPERIMENTALParticipants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase.
Selonsertib 6 mgEXPERIMENTALParticipants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
Selonsertib 18 mgEXPERIMENTALParticipants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase.
PlaceboEXPERIMENTALParticipants will receive selonsertib placebo for 24 weeks, and may then be rerandomized 1:1:1 to selonsertib 2, 6, or 18 mg during the long-term treatment phase.
Placebo to match selonsertibPLACEBO_COMPARATORParticipants will receive placebo to match selonsertib for 48 weeks.
Moderate hepatic impairment (Cohort 1)EXPERIMENTALParticipants with moderate hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.
Severe hepatic impairment (Cohort 2)EXPERIMENTALParticipants with severe hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.
Mild hepatic impairment (Cohort 3)EXPERIMENTALParticipants with mild hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1.

Interventions

NameTypeDescription
SelonsertibDRUG18 mg tablet administered orally once daily
PrednisoloneDRUG40 mg (4 x 10 mg tablets) administered orally once daily
PlaceboDRUGSelonsertib placebo tablet administered orally once daily
Placebo to match selonsertibDRUGTablets administered orally once daily
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Eligibility Criteria

Age Range18 Years to 70 Years
SexALL
Healthy VolunteersNo
Study Sites44

Key Inclusion Criteria: * Willing and able to give informed consent prior to any study specific procedures being performed. In individuals with hepatic encephalopathy (HE) which may impair decision-making, consent will be obtained per hospital procedures (eg, by Legally Authorized Representative) *...

Countries:United StatesAustriaBelgiumCanadaFranceSwitzerlandUnited KingdomGermanyItalyNetherlandsSpain
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Frequently asked questions about Selonsertib

What is Selonsertib used for?

Selonsertib is an investigational small molecule being studied for Diabetic Kidney Disease, Pulmonary Arterial Hypertension, and Alcoholic Hepatitis (AH). It is developed by Gilead Sciences, Inc. (GILD) and is currently in Phase 2 clinical development.

What does Selonsertib target?

Selonsertib is an investigational small molecule. Its molecular target has not been disclosed in available information, so its mechanism of action is not described here.

Who makes Selonsertib?

Selonsertib is being developed by Gilead Sciences, Inc., a biopharmaceutical company traded on NASDAQ under the ticker GILD. The drug is currently in Phase 2 clinical trials for multiple indications.

What phase is Selonsertib in?

Selonsertib is in Phase 2 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Completed Phase 2 trials have evaluated it in Diabetic Kidney Disease, Pulmonary Arterial Hypertension, and Alcoholic Hepatitis.

What clinical trials is Selonsertib in?

Selonsertib has been studied in several completed trials, including NCT02177786 for Diabetic Kidney Disease, NCT02234141 for Pulmonary Arterial Hypertension, and NCT02854631 for Alcoholic Hepatitis. A Phase 1 pharmacokinetic study, NCT02509624, was also completed.

Is Selonsertib the same as GS-4997?

Yes, Selonsertib is also known as GS-4997. Clinical trial records refer to the drug as Selonsertib (GS-4997), confirming that these names refer to the same investigational compound.