Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT04971785 | Study of Semaglutide, and Cilofexor/Firsocostat, Alone and in Combination, in Adults With Cirrhosis Due to Nonalcoholic Steatohepatitis (NASH) | PHASE2 | COMPLETED | 457 | — | — | Aug 9, 2021 | Dec 9, 2024 | Nov 26, 2025 | 242 | United States, Australia +5 |
| NCT03987074 | Safety, Tolerability, and Efficacy of Monotherapy and Combination Regimens in Participants With Nonalcoholic Steatohepatitis (NASH) | PHASE2 | COMPLETED | 109 | — | — | Jul 29, 2019 | Jul 13, 2020 | Jul 15, 2021 | 18 | United States |
Fibrosis improvement was defined as ≥ 1-stage decrease from baseline in fibrosis according to the NASH clinical research network (CRN) classification. Worsening of NASH was defined as ≥ 1-point increase from baseline in hepatocellular ballooning or lobular inflammation. Clopper-Pearson method was used in outcome measure analysis in each arm. Percentages were rounded-off.
Treatment-emergent adverse events (TEAEs) were defined as, 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. Participants were assessed for AEs according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Treatment-emergent laboratory abnormalities, defined as values that increase at least one toxicity grade from baseline at any time post-baseline up to and including the date of last dose of study drug plus 30 days, were summarized by treatment group. Graded laboratory abnormalities were defined using the grading scheme in the CTCAE 5.0.
| Arm | Type | Description |
|---|---|---|
| SEMA + CILO/FIR FDC | EXPERIMENTAL | Participants will receive semaglutide (SEMA) 3.0 mg/mL, once weekly and cilofexor and firsocostat (CILO/FIR) 30 mg/20 mg fixed-dose combination (FDC) tablet, once daily up to 72 weeks. |
| SEMA + PTM CILO/FIR | EXPERIMENTAL | Participants will receive SEMA 3.0 mg/mL, once weekly and Placebo-To-Match (PTM) CILO/FIR FDC tablet, once daily up to 72 weeks. |
| PTM SEMA + CILO/FIR FDC | EXPERIMENTAL | Participants will receive PTM SEMA, once weekly and CILO/FIR 30 mg/20 mg FDC tablet, once daily up to 72 weeks. |
| PTM SEMA + PTM CILO/FIR | PLACEBO_COMPARATOR | Participants will receive PTM SEMA, once weekly and PTM CILO/FIR FDC tablet, once daily up to 72 weeks. |
| Semaglutide | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) for 24 weeks |
| Semaglutide + Firsocostat 20 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg for 24 weeks |
| Semaglutide + Cilofexor 30 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 30 mg for 24 weeks |
| Semaglutide + Cilofexor 100 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + cilofexor 100 mg for 24 weeks |
| Semaglutide + Firsocostat 20 mg + Cilofexor 30 mg | EXPERIMENTAL | Semaglutide 0.24 mg - 2.4 mg (dose escalated over 16 weeks) + firsocostat 20 mg + cilofexor 30 mg for 24 weeks |
| Name | Type | Description |
|---|---|---|
| Semaglutide (SEMA) | DRUG | Administered as subcutaneous (SC) injection |
| Cilofexor (CILO)/Firsocostat (FIR) | DRUG | Tablets administered orally |
| PTM SEMA | DRUG | Administered as SC injection |
| PTM CILO/FIR | DRUG | Tablets administered orally |
| Semaglutide | DRUG | Solution administered subcutaneously with pre-filled PDS290 pen-injector once weekly |
| Firsocostat | DRUG | Tablets administered orally once daily |
| Cilofexor | DRUG | Tablets administered orally once daily |
Key Inclusion Criteria: * Liver biopsy consistent with cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH) in the opinion of the central reader. In individuals who have never had a liver biopsy, a screening liver biopsy may be performed. * Screening laboratory parameters as determined by the ...