Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Seladelpar · 7 trials · 4 indications
EFS as measured by the time from start of treatment to the first occurrence of any of the following clinical events: 1. Death by any cause; 2. Liver transplantation; 3. MELD score ≥15; 4. Ascites requiring treatment; 5. Hospitalization for any of the following: 1. Esophageal or gastric variceal bleeding 2. Hepatic encephalopathy 3. Spontaneous bacterial peritonitis
Percentages were rounded-off.
Percentages were rounded-off.
Treatment-emergent graded laboratory abnormalities were defined as values that increase at least 2 toxicity grade from baseline at any time post baseline. The laboratory abnormalities were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), where Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: potentially life-threatening laboratory abnormality. The data is reported for shift of ≥ 2 grades from baseline in values for hematology and select liver biochemistry. Hematology includes parameters like RBCs, (erythrocytes), hemoglobin, hematocrit, platelets, WBC, WBC differentials (absolute and percentage) including basophils, neutrophils, lymphocytes, eosinophils, and monocytes, etc. Biochemistry included select liver function tests like blood bilirubin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase. Percentages were rounded-off.
Percentage of Participants with Response to Composite Endpoint of ALP \<1.67 × Upper Limit of Normal \[ULN\], ≥15% reduction in ALP, and total bilirubin ≤ ULN) at Month 3. The mITT analysis set included all randomized subjects who received at least one study drug dose. The primary endpoint was analyzed using Cochran-Mantel-Haenszel (CMH) test adjusted for both randomization stratification variables (ALP level: \<350 U/L and 2:350 U/L; pruritus NRS: \<4 and 2:4). The CMH tests were performed for the comparison of 10 mg versus placebo and 5 mg/10 mg versus placebo separately.
Cmax is defined as the maximum observed plasma concentration of the study drug.
Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.
AUC0-t is defined as area under the concentration--time curve from time zero to the last measurable concentration.
AUC0-inf is defined as area under the concentration--time curve from time zero extrapolated to infinity, calculated as AUC0-t+Ct/Kel, where: Ct = the last measurable concentration and Kel = elimination rate constant.
Cmax is defined as the maximum observed plasma concentration of the study drug.
Cmax,ss is defined as the steady-state maximum observed plasma concentration of the study drug at Day 28.
Tmax is defined as the time to reach the maximum observed plasma concentration of the study drug.
Tmax,ss is defined as the steady-state time to reach maximum observed plasma concentration of the study drug at Day 28.
AUC0-24 is defined as area under the concentration-time curve from time zero to 24 hours.
AUCtau is defined as the area under the drug concentration versus time curve over the dosing interval.
RCmax is defined as the accumulation ratio based on Cmax, calculated as Cmax on Day 28/ Day 1.
RAUC0-t is defined as the accumulation ratio based on AUC0-t, calculated as AUC0-tau on Day 28/ AUC0-24 on Day 1 for participants with dose once a day.
An adverse event (AE) was defined as any medical occurrence in a participant administered to a pharmaceutical product in a clinical study, regardless of a causal relationship with this treatment. TEAEs were defined as AEs that commenced or worsened on or after the time of study drug administration in Part A until up to 30 days after study drug administration in Part A or before the first study drug administration in Part B (whichever is earlier). For Part B, TEAEs are defined as AEs that commence or worsen on or after the time of first study drug administration in Part B until up to 30 days after the last study drug administration in Part B. A drug-related TEAE was defined as TEAE which was related (reported as 'possible', 'probable', or 'definite') to study drug. Percentages were rounded off.
TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced. The percentage of participants with any severity grade and severity grade of 3 or 4 were reported. Percentages were rounded off.
TEAEs of special interest for this study were defined as AEs that met CTCAE version 5.0 or the most recent version Grade 2 criteria or higher for AEs of elevated alanine transaminase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine kinase, lipase, or serum creatinine. Hepatic decompensation clinical events including ascites, jaundice, esophageal variceal bleeding, and hepatic encephalopathy, were also defined as TEAEs of special interest for this study. Percentages were rounded off.
Vital signs (including oral temperature, respiratory rate, seated blood pressure \[diastolic and systolic\], and heart rate) were evaluated. Percentage of participants with clinically significant changes in vital signs evaluations was reported. The clinically significant changes were based on investigator's judgement.
ECG measurements included the parameters of heart rate, ventricular rate, PR interval, QRS duration, QT interval (uncorrected), and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Per protocol, ECG findings were classified in 1 of 3 categories: normal, abnormal but not clinically significant, or abnormal and clinically significant. Any abnormality in ECG assessments which were deemed clinically significant by the investigator were reported.
Clinical laboratory parameters included biochemistry, hematology, coagulation, and urinalysis. Abnormal laboratory values were graded according to the NCI CTCAE version 5.0.Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. The percentage of participants with a shift of ≥ 2 NCI CTCAE grade from baseline was reported.
| Arm | Type | Description |
|---|---|---|
| Seladelpar | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| Seladelpar 5-10 mg | EXPERIMENTAL | - |
| Seladelpar 10 mg | EXPERIMENTAL | - |
| Seladelpar 5 mg Capsules | EXPERIMENTAL | - |
| Seladelpar 10 mg Capsule | EXPERIMENTAL | - |
| Part A: Cohort 1 - CP-A Without PHT (Seladelpar 10 mg) | EXPERIMENTAL | Participants with primary biliary cholangitis (PBC) and a Child-Pugh (CP) classification of CP-A (score 5 to 6) without portal hypertension (PHT) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 2 - CP-A With PHT (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 3 - CP-B (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-B (score 7 to 9) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Part A: Cohort 4 - CP-C (Seladelpar 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-C (score 10 to 12) will receive a single dose of seladelpar 10 mg, orally, on Day 1. |
| Experimental: Part B: Cohort 2 - CP-A With PHT (Seladelpar 5 mg or 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-A (score 5 to 6) with PHT, who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
| Experimental: Part B: Cohort 3 - CP-B (Seladelpar 5 mg or 10 mg) | EXPERIMENTAL | Participants with PBC and a CP classification of CP-B (score 7 to 9), who complete Part A, will receive seladelpar 10 mg or 5 mg, orally, once daily, for 28 days. Doses for Part B will be chosen based on exposure from a single dose in Part A for individual participants. |
| Normal | EXPERIMENTAL | Child-Pugh Score: N/A Subjects will receive a single 10 mg oral dose of seladelpar |
| Mild Impairment | EXPERIMENTAL | Child-Pugh Score: A (5 to 6 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Moderate Impairment | EXPERIMENTAL | Child-Pugh Score: B (7 to 9 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Severe Impairment | EXPERIMENTAL | Child-Pugh Score: C (10 to 15 points) Subjects will receive a single 10 mg oral dose of seladelpar |
| Name | Type | Description |
|---|---|---|
| Seladelpar | DRUG | * Seladelpar 10 mg one capsule daily for up to 36 months in participants with CP-A cirrhosis or * Seladelpar 5 mg one capsule daily for up to 36 months in participants with CP-B cirrhosis. |
| Placebo | DRUG | One capsule daily for up to 36 months. |
| Seladelpar 10 mg | DRUG | Administered orally |
| Seladelpar 5 mg | DRUG | If down-titration needed, one capsule daily for double-blind period, for a duration of up to 12 months |
| seladelpar 5-10 mg | DRUG | Seladelpar 5 mg for 6 months and then titrating up to 10 mg based on tolerability and response for remainder of double-blind period. After completion of the 1-year double-blind period subjects will be offered the opportunity to enter an open label long term safety study. Subjects will continue the seladelpar dose (5 or 10 mg) received during the double-blinded study |
| Seladelpar 5 mg Capsule | DRUG | Participants will be assigned to a treatment group if tolerability issues noted in the previous study. |
| Seladelpar 10 mg Capsule | DRUG | Participants will be assigned to a treatment group unless there are tolerability issues. |
Inclusion Criteria: Individuals must meet the following criteria to be eligible for study participation: 1. Must be at least 18 years old. 2. Must have a confirmed prior diagnosis of PBC 3. Evidence of cirrhosis 4. CP Score A or B 5. Females of reproductive potential must use at least 1 barrier co...
Seladelpar is an investigational small molecule being developed for Primary Biliary Cholangitis (PBC), also referred to as Primary Biliary Cirrhosis, and for Hepatic Impairment. It is currently in Phase 3 clinical development and is not yet approved by the FDA.
Seladelpar is being developed by Gilead Sciences, Inc., which trades on the NASDAQ under the ticker symbol GILD. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with Primary Biliary Cholangitis and Hepatic Impairment.
Seladelpar is in Phase 3 clinical development for Primary Biliary Cholangitis. It has completed Phase 1 studies in hepatic impairment and is also being evaluated in an additional Phase 3 trial. The drug remains investigational and has not received FDA approval.
Seladelpar is being studied in several clinical trials, including NCT03301506, a Phase 3 study in Primary Biliary Cholangitis with 340 participants, and NCT06060665, a Phase 3 study on alkaline phosphatase normalization. Phase 1 trials include NCT03369002 and NCT04950764, which evaluate the drug in hepatic impairment.
Yes, Seladelpar is also known as Seladelpar 5 mg Capsule. This alternative name refers to the specific dosage form being tested in clinical trials for Primary Biliary Cholangitis and Hepatic Impairment.
No, Seladelpar is not FDA approved. It is an investigational drug currently in Phase 3 clinical trials for Primary Biliary Cholangitis. The drug has not completed the regulatory review process, and its safety and efficacy have not been fully established.