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

NCT ID: NCT03551522

Last Updated: 2022-09-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-30
• Study Completion Date: 2020-08-10

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

Detailed Description

Primary Objectives

1. To 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 DB phase

2. To evaluate the safety and tolerability of seladelpar in the DB and OLE phases

Secondary Objectives

1. To evaluate the effect of seladelpar on MRI- PDFF at Week 26 and Week 52 in the DB phase

2. To evaluate the effect of seladelpar on histological improvement of nonalcoholic fatty liver disease activity score (NAS) at Week 52 in the DB phase

3. To evaluate the effect of seladelpar on histological improvement of fibrosis at Week 52 in the DB phase

4. To evaluate the effect of seladelpar on metabolic biochemical markers and biochemical markers of inflammation in the DB and OLE phases

Conditions

NASH - Nonalcoholic Steatohepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Seladelpar 10 mg

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

Group Type: EXPERIMENTAL

Seladelpar

Intervention Type: DRUG

10 mg, 20 mg, or 50 mg

Seladelpar 20 mg

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

Group Type: EXPERIMENTAL

Seladelpar

Intervention Type: DRUG

10 mg, 20 mg, or 50 mg

Seladelpar 50 mg

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

Group Type: EXPERIMENTAL

Seladelpar

Intervention Type: DRUG

10 mg, 20 mg, or 50 mg

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebos

Intervention Type: DRUG

Matching placebo Capsule

Interventions

Seladelpar

10 mg, 20 mg, or 50 mg

Intervention Type: DRUG

Placebos

Matching placebo Capsule

Intervention Type: DRUG

Other Intervention Names

MBX-8025

Eligibility Criteria

Inclusion Criteria

1. Must be able to provide written informed consent (signed and dated) and any authorizations required by local law

2. 18 to 75 years old (inclusive)

3. 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)

4. NAS of 4 points or greater with a score of at least 1 point in each component (steatosis, lobular inflammation, and ballooning)

5. Fibrosis stage 1, 2, or 3 on liver biopsy

6. MRI-PDFF ≥ 10%

7. 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.

Exclusion Criteria

1. 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

2. 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

3. Treatment with pioglitazone or high-dose vitamin E (>400 IU/day) within the last 2 months prior to the initial screening

4. 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

5. Prior or planned bariatric surgery (a prior reversed sleeve gastrectomy is permitted)

6. Poorly controlled type 2 diabetes mellitus as defined by hemoglobin A1c [HbA1c] 9.5% or higher or type 1 diabetes mellitus

7. 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

8. Significant weight loss within the last 6 months (e.g., > 10%)

9. Use of any weight-loss medication for 3 months prior to and during the study period

10. Body mass index (BMI) < 18.5 kg/m2

11. 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

12. Other chronic liver diseases

• Active hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
• Active hepatitis C as defined by presence of hepatitis C virus antibody (HCV AB) plus a positive HCV RNA
• History or evidence of current active autoimmune hepatitis
• History or evidence of primary biliary cholangitis (PBC)
• History or evidence of primary sclerosing cholangitis
• History or evidence of Wilson's disease
• History or evidence of alpha-1-antitrypsin deficiency
• History or evidence of hemochromatosis
• History or evidence of drug-induced liver disease, as defined exposure and history
• Known bile duct obstruction
• Suspected or proven liver cancer

13. ALT > 200 U/L

14. AST < 20 U/L

15. Creatine kinase (CK) > upper limit of normal (ULN)

16. Serum creatinine > ULN

17. Platelet < lower limit of normal (LLN)

18. Inability to obtain a liver biopsy

19. History of biliary diversion

20. Known history of human immunodeficiency virus (HIV) infection

21. History of malignancy diagnosed or treated within 2 years

• Recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted
• Cervical carcinoma in-situ is allowed if appropriately treated prior to Screening
• Participants under active evaluation for malignancy are not eligible

22. Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening

23. Females who are pregnant or breastfeeding

24. Patients unable to undergo MRI-PDFF due to:

• Contraindication to MRI examination
• Severe claustrophobia impacting ability to perform MRI during the study, despite mild sedation/treatment with an anxiolytic
• Weight or girth exceeds the scanner capacities

25. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whichever is longer, prior to the initial screening

26. Active, serious medical disease with likely life expectancy < 5 years

27. Any other condition(s) that would compromise the safety of the subject or compromise study quality as judged by the Investigator

OLE Phase Enrollment Criteria

Subjects must fulfill the following before allowing to start OLE dosing:

1. Provide informed consent on or before Day 1 and prior to any OLE-related study procedures.

2. Completed through the Week 52 biopsy and Week 56 lab assessments in the DB phase

• AST < 20 U/L
• Inability to obtain a liver biopsy (no new biopsy required for OLE)
• Unable to undergo MRI-PDFF (no imaging performed in OLE)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

CymaBay Research Site

Glendale, Arizona, United States

CymaBay Research Site

Tucson, Arizona, United States

CymaBay Research Site

Los Angeles, California, United States

CymaBay Research Site

Boca Raton, Florida, United States

CymaBay Research Site

Lakewood Rch, Florida, United States

CymaBay Research Site

Flowood, Mississippi, United States

CymaBay Research Site

Clarksville, Tennessee, United States

CymaBay Research Site

Germantown, Tennessee, United States

CymaBay Research Site

Hermitage, Tennessee, United States

CymaBay Research Site

Knoxville, Tennessee, United States

CymaBay Research Site

Chandler, Texas, United States

CymaBay Research Site

Dallas, Texas, United States

CymaBay Research Site

Live Oak, Texas, United States

CymaBay Research Site

Rollingwood, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 39326675 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33793651 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CB8025-21730

Identifier Type: -

Identifier Source: org_study_id