Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as GS-4997, SEL
Selonsertib · 4 trials · 3 indications
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.
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.
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).
AUCinf is defined as the concentration of drug extrapolated to infinite time.
AUClast is defined as the concentration of drug from time zero to the last observable concentration.
Cmax is defined as the maximum concentration of drug.
| Arm | Type | Description |
|---|---|---|
| Selonsertib + Prednisolone | EXPERIMENTAL | Selonsertib + prednisolone for 28 days |
| Prednisolone | PLACEBO_COMPARATOR | Selonsertib placebo + prednisolone for 28 days |
| Selonsertib 2 mg | EXPERIMENTAL | Participants will receive selonsertib 2 milligrams (mg) for 24 weeks and may continue on this dose during the long-term treatment phase. |
| Selonsertib 6 mg | EXPERIMENTAL | Participants will receive selonsertib 6 mg for 24 weeks and may continue on this dose during the long-term treatment phase. |
| Selonsertib 18 mg | EXPERIMENTAL | Participants will receive selonsertib 18 mg for 24 weeks and may continue on this dose during the long-term treatment phase. |
| Placebo | EXPERIMENTAL | Participants 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 selonsertib | PLACEBO_COMPARATOR | Participants will receive placebo to match selonsertib for 48 weeks. |
| Moderate hepatic impairment (Cohort 1) | EXPERIMENTAL | Participants with moderate hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
| Severe hepatic impairment (Cohort 2) | EXPERIMENTAL | Participants with severe hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
| Mild hepatic impairment (Cohort 3) | EXPERIMENTAL | Participants with mild hepatic impairment and matched healthy controls will receive a single dose of selonsertib on Day 1. |
| Name | Type | Description |
|---|---|---|
| Selonsertib | DRUG | 18 mg tablet administered orally once daily |
| Prednisolone | DRUG | 40 mg (4 x 10 mg tablets) administered orally once daily |
| Placebo | DRUG | Selonsertib placebo tablet administered orally once daily |
| Placebo to match selonsertib | DRUG | Tablets administered orally once daily |
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) *...
Selonsertib is an investigational small molecule developed by Gilead Sciences, Inc. (GILD). It has been studied in clinical trials for alcoholic hepatitis, diabetic kidney disease, and pulmonary arterial hypertension. Selonsertib is not approved and remains in clinical development, with Phase 2 studies completed in these indications.
Selonsertib targets MAP3K5, also known as apoptosis signal-regulating kinase 1 (ASK1). It acts as an inhibitor of this kinase. By inhibiting MAP3K5, selonsertib is designed to modulate stress-response signaling pathways involved in inflammation and fibrosis, which are relevant to the diseases it has been studied in.
Selonsertib is made by Gilead Sciences, Inc., which trades on the Nasdaq under the ticker GILD. Gilead developed and sponsored the clinical trials evaluating selonsertib in alcoholic hepatitis, diabetic kidney disease, and pulmonary arterial hypertension.
Selonsertib is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA for any indication. The completed trials include Phase 2 studies in alcoholic hepatitis, diabetic kidney disease, and pulmonary arterial hypertension, as well as a Phase 1 pharmacokinetic study.
Selonsertib has been evaluated in completed trials including NCT02854631, a Phase 2 study in severe alcoholic hepatitis combining selonsertib with prednisolone; NCT02234141, a Phase 2 trial in pulmonary arterial hypertension; NCT02177786, a Phase 2 trial in diabetic kidney disease; and NCT02509624, a Phase 1 pharmacokinetic study in participants with normal and impaired hepatic function.
Yes, Selonsertib is also known as GS-4997. GS-4997 is the code name used in some trial titles, such as the Phase 2 study NCT02177786 in diabetic kidney disease. Both names refer to the same investigational small molecule developed by Gilead Sciences.