A Study to Evaluate Seladelpar in Subjects With Nonalcoholic Steatohepatitis (NASH)

NCT03551522 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: CB8025-21730
• Study Type: interventional
• Target: 181
• Locations: 1 country
• Sites: 14

Brief Summary

A Phase 2, Double-Blind (DB), Randomized, Placebo-Controlled Study Followed by an Open-Label Extension Period to Evaluate the Activity of Seladelpar in Subjects with Nonalcoholic Steatohepatitis (NASH) OLE phase was not analyzed due to the early termination of the study

Conditions

NASH - Nonalcoholic Steatohepatitis

Outcome Measures

Primary Outcomes (1)

• Percentage Change From Baseline in Magnetic Resonance Imaging-proton Density Fat Fraction (MRI-PDFF)

  Evaluate the effect of seladelpar on hepatic fat fraction, as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) at Week 12 in the double-blind (DB) phase. MRI-PDFF Relative (Percent) Change From Baseline to Week 12 - ANCOVA - mITT Population MRI-PDFF exam was used to quantify the hepatic proton density fat fraction noninvasively. The fat fraction is the proportion of mobile protons in liver tissue attributable to fat and thus, is a noninvasive magnetic resonance-based biomarker of liver triglyceride concentration.

  Week 12

Secondary Outcomes (8)

• Percentage of Participants With Improvement of 2 Points or More in the Nonalcoholic Fatty Liver Disease Activity Score (NAS)

  Week 52

• Percent Change From Baseline in Alanine Aminotransferase (ALT) at Week 12 and Week 52

  Week 12, Week 52

• Percent Change From Baseline in Aspartate Aminotransferase (AST) at Week 12 and Week 52

  Weeks 12, Week 52

• Percent Change From Baseline in Gamma Glutamyl Transferase (GGT) at Week 12 and Week 52

  Weeks 12, Week 52

• Number of Participants With Decrease in MRI-PDFF ≥ 30% From Baseline at Week 12 and Week 52

  Week 12, Week 52

Study Arms (4)

Seladelpar 10 mg

EXPERIMENTAL

Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.

Drug: Seladelpar

Seladelpar 20 mg

EXPERIMENTAL

Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.

Drug: Seladelpar

Seladelpar 50 mg

EXPERIMENTAL

Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.

Drug: Seladelpar

Placebo

PLACEBO COMPARATOR

Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.

Drug: Placebos

Interventions

Seladelpar DRUG

10 mg, 20 mg, or 50 mg

Also known as: MBX-8025

Seladelpar 10 mg; Seladelpar 20 mg; Seladelpar 50 mg

Placebos DRUG

Matching placebo Capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be able to provide written informed consent (signed and dated) and any authorizations required by local law
• to 75 years old (inclusive)
• Histological evidence of definite NASH on a liver biopsy (obtained during the screening period or historical liver biopsy obtained no more than 90 days prior to the initial screening visit)
• NAS of 4 points or greater with a score of at least 1 point in each component (steatosis, lobular inflammation, and ballooning)
• Fibrosis stage 1, 2, or 3 on liver biopsy
• MRI-PDFF ≥ 10%
• Females of reproductive potential must use at least one barrier contraceptive and a second effective birth control method during the study and for at least 30 days after the last dose of study drug. Male subjects who are sexually active with female partners of reproductive potential must use barrier contraception and their female partners must use a second effective birth control method during the study and for at least 90 days after the last dose of study drug.

You may not qualify if:

• Significant alcohol consumption, defined as more than 2 drink units per day (equivalent to 20 g) in women and 3 drink units per day (equivalent to 30 g) in men, or inability to reliably quantify alcohol intake
• Treatment with drugs associated with nonalcoholic fatty liver disease (NAFLD) (amiodarone, methotrexate, oral glucocorticoids at doses greater than 5 mg/day, tamoxifen, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids (such as testosterone and valproic acid) for more than 4 weeks within the last 2 months prior to the initial screening
• Treatment with pioglitazone or high-dose vitamin E (\>400 IU/day) within the last 2 months prior to the initial screening
• Initiation of treatment with a glucagon-like peptide-1 (GLP-1) agonist or a dose change within the last 2 months prior to the initial screening
• Prior or planned bariatric surgery (a prior reversed sleeve gastrectomy is permitted)
• Poorly controlled type 2 diabetes mellitus as defined by hemoglobin A1c \[HbA1c\] 9.5% or higher or type 1 diabetes mellitus
• Diabetic patients who are taking sodium/glucose cotransporter 2 (SGLT-2) inhibitors must be on a stable dose within 2 months prior to the initial screening and throughout the study
• Significant weight loss within the last 6 months (e.g., \> 10%)
• Use of any weight-loss medication for 3 months prior to and during the study period
• Body mass index (BMI) \< 18.5 kg/m2
• Hepatic decompensation defined as the presence of any of the following:
• Serum albumin less than 3.5 g/dL
• International normalized ratio (INR) greater than 1.4 (unless due to therapeutic anticoagulants)
• Total bilirubin greater than 2 mg/dL with the exception of Gilbert syndrome
• History of esophageal varices, ascites, or hepatic encephalopathy

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (14)

CymaBay Research Site

Glendale, Arizona, 85306, United States

Location

CymaBay Research Site

Tucson, Arizona, 85712, United States

Location

CymaBay Research Site

Los Angeles, California, 90057, United States

Location

CymaBay Research Site

Boca Raton, Florida, 33434, United States

Location

CymaBay Research Site

Lakewood Rch, Florida, 34211, United States

Location

CymaBay Research Site

Flowood, Mississippi, 39232, United States

Location

CymaBay Research Site

Clarksville, Tennessee, 37040, United States

Location

CymaBay Research Site

Germantown, Tennessee, 38138, United States

Location

CymaBay Research Site

Hermitage, Tennessee, 37076, United States

Location

CymaBay Research Site

Knoxville, Tennessee, 37909, United States

Location

CymaBay Research Site

Chandler, Texas, 85224, United States

Location

CymaBay Research Site

Dallas, Texas, 75246, United States

Location

CymaBay Research Site

Live Oak, Texas, 78233, United States

Location

CymaBay Research Site

Rollingwood, Texas, 78746, United States

Location

Related Publications (2)

• Alkhouri N, Beyer C, Shumbayawonda E, Andersson A, Yale K, Rolph T, Chung RT, Vuppalanchi R, Cusi K, Loomba R, Pansini M, Dennis A. Decreases in cT1 and liver fat content reflect treatment-induced histological improvements in MASH. J Hepatol. 2025 Mar;82(3):438-445. doi: 10.1016/j.jhep.2024.08.031. Epub 2024 Sep 25.

  PMID: 39326675 DERIVED

• Beyer C, Hutton C, Andersson A, Imajo K, Nakajima A, Kiker D, Banerjee R, Dennis A. Comparison between magnetic resonance and ultrasound-derived indicators of hepatic steatosis in a pooled NAFLD cohort. PLoS One. 2021 Apr 1;16(4):e0249491. doi: 10.1371/journal.pone.0249491. eCollection 2021.

  PMID: 33793651 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

seladelpar; (2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Barry Crittenden, Vice President of Clinical Development
• Organization: CymaBay Therapeutics, Inc.

medinfo@cymabay.com

510-293-8800

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind Placebo Controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomization: 1:2:2:2 (placebo: seladelpar 10 mg: 20 mg: 50 mg)

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: June 11, 2018
• Study Start: April 30, 2018
• Primary Completion: May 8, 2019
• Study Completion: August 10, 2020
• Last Updated: September 15, 2022
• Results First Posted: July 5, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)