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

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ClinicalTrials.gov Identifier: NCT03551522
Recruitment Status : Active, not recruiting
First Posted : June 11, 2018
Last Update Posted : March 5, 2019
Sponsor:
Information provided by (Responsible Party):
CymaBay Therapeutics, Inc.

Brief Summary:
A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Activity of Seladelpar in Subjects with Nonalcoholic Steatohepatitis (NASH)

Condition or disease Intervention/treatment Phase
NASH - Nonalcoholic Steatohepatitis Drug: Seladelpar Drug: Placebos Phase 2

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
  2. To evaluate the safety and tolerability of seladelpar in subjects with NASH

Secondary Objectives

  1. To evaluate the effect of seladelpar on hepatic fat fraction, as assessed by MRI- PDFF at Week 26 and Week 52
  2. To evaluate the effect of seladelpar on histological improvement of nonalcoholic fatty liver disease activity score (NAS) after 52 weeks of treatment
  3. To evaluate the effect of seladelpar on histological improvement of fibrosis after 52 weeks of treatment
  4. To evaluate the effect of seladelpar on metabolic biochemical markers and biochemical markers of inflammation over 52 weeks of treatment

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomization: 1:2:2:2 (placebo: seladelpar 10 mg: 20 mg: 50 mg)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double Blind Placebo Controlled
Primary Purpose: Treatment
Official Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Activity of Seladelpar in Subjects With Nonalcoholic Steatohepatitis (NASH)
Actual Study Start Date : April 30, 2018
Estimated Primary Completion Date : April 30, 2019
Estimated Study Completion Date : December 31, 2020


Arm Intervention/treatment
Experimental: Seladelpar 10 mg
Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.
Drug: Seladelpar
10 mg, 20 mg, or 50 mg
Other Name: MBX-8025

Experimental: Seladelpar 20 mg
Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.
Drug: Seladelpar
10 mg, 20 mg, or 50 mg
Other Name: MBX-8025

Experimental: Seladelpar 50 mg
Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.
Drug: Seladelpar
10 mg, 20 mg, or 50 mg
Other Name: MBX-8025

Placebo Comparator: Placebo
Subjects enrolled will receive seladelpar 10 mg, 20 mg, 50 mg or placebo daily for 52 weeks.
Drug: Placebos
Matching placebo Capsule




Primary Outcome Measures :
  1. Relative change in MRI-PDFF at Week 12 [ Time Frame: Baseline and 12 Weeks ]
  2. Adverse events (AEs) [ Time Frame: 52 Weeks ]
  3. Treatment emergent adverse events (TEAEs) [ Time Frame: 52 Weeks ]
  4. electrocardiograms (ECGs) [ Time Frame: 52 Weeks ]
    clinically significant versus not clinically significant

  5. biochemistry [ Time Frame: 52 Weeks ]
    National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Grade 1 through 5, Version 4.0

  6. hematology [ Time Frame: 52 Weeks ]
    National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Grade 1 through 5, Version 4.0


Secondary Outcome Measures :
  1. Absolute change in MRI-PDFF at Week 12, 26, and 52 [ Time Frame: Week 12, Week 26 and Week 52 ]
  2. Relative change in MRI-PDFF at Week 26 and 52 [ Time Frame: Week 26 and Week 52 ]
  3. Proportion of subjects with a relative decrease in MRI-PDFF ≥ 30% at Week 12, 26, and 52 [ Time Frame: Week 12, Week 26 and Week 52 ]
  4. Proportion of subjects with normalization of MRI-PDFF (defined as a fat fraction of < 5%) at Week 12, 26, and 52 [ Time Frame: Week 12, Week 26 and Week 52 ]
  5. Proportion of subjects with an absolute MRI-PDFF change > 5% at Weeks 12, 26, and 52 [ Time Frame: Week 12, Week 26 and Week 52 ]
  6. Proportion of subjects with reversal of NASH and no worsening of hepatic fibrosis (centrally scored histology at 52 weeks). [ Time Frame: Week 52 ]
    The reversal of NASH is defined as the absence of hepatocellular ballooning (score of 0) and no or minimal inflammation (score of 0 or 1)

  7. Proportion of subjects with improvement by at least one stage in fibrosis without worsening of NASH [ Time Frame: Week 52 ]
  8. Proportion of subjects with a 2-point improvement in NAS [ Time Frame: Week 52 ]
  9. Percent and absolute change in alanine aminotransferase (ALT) [ Time Frame: Baseline and Week 52 ]
  10. Percent and absolute change in aspartate aminotransferase (AST) [ Time Frame: Baseline and Week 52 ]
  11. Percent and absolute change in gamma-glutamyl transferase (GGT) [ Time Frame: Baseline and Week 52 ]
  12. Percent and absolute change in total cholesterol (TC) [ Time Frame: Baseline and Week 52 ]
  13. Percent and absolute change in high-density lipoprotein cholesterol (HDL-C) [ Time Frame: Baseline and Week 52 ]
  14. Percent and absolute change in low-density lipoprotein cholesterol (LDL-C) [ Time Frame: Baseline and Week 52 ]
  15. Percent and absolute change in non-high-density lipoprotein cholesterol (non-HDL) [ Time Frame: Baseline and Week 52 ]
  16. Percent and absolute change in homeostatic model assessment of insulin resistance (HOMA-IR) [ Time Frame: Baseline and Week 52 ]
  17. Percent and absolute change in high-sensitivity C-reactive protein (Hs-CRP) [ Time Frame: Baseline and Week 52 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must have given 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 or greater with a score of at least 1 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 90 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, 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 (hemoglobin A1c [HbA1c] 9.5% or higher) or type 1 diabetes mellitus
  7. Diabetic patients who are taking sodium/glucose cotransporter (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. Body mass index (BMI) < 18.5 kg/m2
  10. 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
  11. Other chronic liver diseases

    • Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
    • Hepatitis C as defined by presence of hepatitis C virus antibody (HCV AB) or positive HCV RNA (tested for known cured HCV infection, or positive HCV AB at screening)
    • 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 on the basis of typical exposure and history
    • Known bile duct obstruction
    • Suspected or proven liver cancer
  12. ALT greater than 200 U/L
  13. AST less than 20 U/L
  14. Creatine kinase (CK) above 1.0 × upper limit of normal (ULN)
  15. Serum creatinine above 1.0 × ULN
  16. Platelet below 1.0 × lower limit of normal (LLN)
  17. Inability to obtain a liver biopsy
  18. History of biliary diversion
  19. Known history of human immunodeficiency virus (HIV) infection
  20. Active, serious medical disease with likely life expectancy < 5 years
  21. Active substance abuse, based on Investigator judgment, including inhaled or injected drugs, within 1 year prior to the initial screening
  22. Females who are pregnant or breastfeeding
  23. 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
  24. Treatment with any other investigational therapy or device within 30 days or within five half-lives, whichever is longer, prior to the initial screening
  25. Any other condition(s) that would compromise the safety of the subject or compromise study quality as judged by the Investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03551522


Locations
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United States, Arizona
CymaBay Research Site
Glendale, Arizona, United States, 85306
CymaBay Research Site
Tucson, Arizona, United States, 85712
United States, California
CymaBay Research Site
Los Angeles, California, United States, 90057
United States, Florida
CymaBay Research Site
Boca Raton, Florida, United States, 33434
CymaBay Research Site
Lakewood Ranch, Florida, United States, 34211
United States, Mississippi
CymaBay Research Site
Flowood, Mississippi, United States, 39232
United States, Tennessee
CymaBay Research Site
Clarksville, Tennessee, United States, 37040
CymaBay Research Site
Germantown, Tennessee, United States, 38138
CymaBay Research Site
Hermitage, Tennessee, United States, 37076
CymaBay Research Site
Knoxville, Tennessee, United States, 37909
United States, Texas
CymaBay Research Site
Chandler, Texas, United States, 85224
CymaBay Research Site
Dallas, Texas, United States, 75246
CymaBay Research Site
Live Oak, Texas, United States, 78233
CymaBay Research Site
Rollingwood, Texas, United States, 78746
Sponsors and Collaborators
CymaBay Therapeutics, Inc.

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Responsible Party: CymaBay Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT03551522     History of Changes
Other Study ID Numbers: CB8025-21730
First Posted: June 11, 2018    Key Record Dates
Last Update Posted: March 5, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases