non-alcoholic steatohepatitis with fibrosis MedDRA version: 22.0 Level: PT Classification code 10053219 Term: Non-alcoholic steatohepatitis System Organ Class: 10019805 - Hepatobiliary disorders MedDRA version: 20.0 Level: PT Classification code 10019668 Term: Hepatic fibrosis System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Product Name: VK2809, 1 mg
Product Code: VK2809
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: VK2809
Other descriptive name: 4-[[4-[[(2R,4S)-4-(3-ch
Sponsors
VIKING THERAPEUTICS, INC.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provide a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study and is willing and able to participate; 2. Have a histologically-confirmed diagnosis of NASH on a liver biopsy performed during screening or within 6 months before screening; for this study, confirmation requires: (a) NASH Clinical Research Network (CRN) fibrosis stage 1 to stage 3 and (b) NASH activity score (NAS) of =4 with at least a score of 1 in each of the following NAS components: ballooning degeneration (score = 0-2), lobular inflammation (score = 0-3) and steatosis (score = 0-3); (c) F1 subjects must have at least one of these risk factors: type 2 diabetes, body mass index of = 30 mg/ m2, and/ or alanine aminotransferase > 1.5 x ULN 3. Have a screening MRI-PDFF with = 8% liver fat fraction; 4. Male and females be 18 to 75 years of age, inclusive, at screening; 5. Be able to comply with contraception restrictions: Female subjects of non-childbearing potential must: (a) have documentation of surgical intervention (i.e., bilateral oophorectomy, hysterectomy, or tubal ligation) or (b) be naturally sterile (i.e., reliable history of >12 consecutive months without menses). Female subjects of childbearing potential must: (c) have a negative serum pregnancy (beta human chorionic gonadotropin) test at screening, (d) have a negative urine pregnancy test documented within the 24-hour period prior to the first dose of investigational product, (e) agree to use two effective methods of contraception from the date of screening until 28 days after the last dose of investigational product; acceptable effective methods of contraception include hormonal contraception intrauterine devices including hormone-containing devices and barrier methods, (f) abstinence is allowed if documented in medical record to be reliable and ongoing for at least 12 months or more and considered appropriate by the investigator. For purposes of the trial, abstinence is defined as a long-term habitual practice if it has been practiced for twelve months or more. Abstinence should be verified by being included in the medical history and the subject must continue abstinence until 28 days after study completion, (g) not be breastfeeding, and (h) not plan to become pregnant during the study; Male subjects who are sexually active with female partners of reproductive potential must: (i) use barrier contraception and their female partners must use a second effective birth control method (see Inclusion Criteria 5 (e) for acceptable, effective contraception methods) during the study and for at least 28 days after the last dose of investigational product; OR (j) have had a vasectomy and use barrier contraception (e.g. condom with spermicide) or their female partners must use an effective birth control method during the study and for at least 28 days after the last dose of investigational product; 6. Subjects with type 2 diabetes must have stable glycemic control defined as screening Hemoglobin A1C < 9%. The following oral agents are permitted as long as treatment has been stable for at least 3 months prior to the qualifying liver biopsy until randomization: (a) biguanides (example: metformin) (b) sulfonylureas (c) DPP4 inhibitors (d) meglitinides (e) a-Glucosidase inhibitors (example: acarbose) (f) bromocriptine (g) SLGT2 inhibitors are permitted as long as treatment has been
Exclusion criteria
Exclusion criteria: Please refer to the protocol for the full exclusion criteria 1. Are unwilling to undergo the required liver biopsy procedures or have any condition that would prevent obtaining a liver biopsy as part of this clinical protocol; 2. Have evidence of current or history of excessive alcohol consumption of more than 20 g per day for women and 30 g per day for men, on average, within 6 months before the qualifying liver biopsy and up to randomization, or are unable to provide a reliable estimate of alcohol consumption during this period; 3. Have evidence (positive drug and alcohol test) of or acknowledge use of illicit drugs and excessive alcohol consumption within 6 months prior to screening with the exception of: (a) use of medical marijuana (b) recreational use of marijuana, if in the opinion of the Investigator it will have no adverse impact on the compliance and safety of the subject in the study; 4. Have had weight change > 5% within 6 months prior to the qualifying liver biopsy and up to randomization; 5. Treatment with medications for the purpose of weight loss within 6 months prior to qualifying liver biopsy, unless approved after consultation with the medical monitor. These include drugs approved for weight loss (e.g. orlistat, bupropion/naltrexone, phentermine-topiramate, phentermine, lorcaserin), as well as drugs used off-label, herbal preparations and dietary supplements marketed for control of body weight or appetite; 6. History of eating disorders; 7. Active involvement in a structured weight loss program (including programs such as Weight Watchers, Jenny Craig, etc.) within 6 months prior to qualifying liver biopsy, unless approved after consultation with the medical monitor; 8. Have a history of: (a) Type 1 diabetes or Latent autoimmune diabetes in adults (LADA) (b) uncontrolled Type 2 diabetes (Hemoglobin A1c =9% at Screening); 9. Have a history of: (a) solid organ or bone marrow transplantation, (b) active thyroid disease including hyperthyroidism, (c) hepatic decompensation (example: including history of esophageal varices, ascites, hepatic encephalopathy, etc.) (d) immunologically-mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatoid arthritis), or (e) osteoporosis; 10. Have a history of effective bariatric surgery prior to qualifying for the study (subjects with ineffective surgery may be able to participate after consultation with the medical monitor), 11. Have a diagnosis (or current evidence) of other chronic liver diseases, including: (a) Hepatitis B (HBV) infection, as defined by presence of hepatitis B surface antigen (HBsAg) (b) HCV, as defined by positive antibody and detectable HCV RNA NOTE: Hep C RNA testing instead of initial screening for HCV antibody positivity must be done in all subjects with prior history of Hep C infection. Subjects with detectable HCV RNA levels within 6 months prior to the qualifying liver biopsy and up to screening will not be eligible to participate; (c) Hepatitis E (HEV) infection NOTE: Hep E testing instead of initial screening for HEV infection positivity must be done in all subjects with prior history of Hep E infection. Subjects with detectable HEV RNA levels within 6 months prior to the qualifying liver biopsy and up to screening will not be eligible to participate; (d) Acute Hepatitis A HAV IgM antibodies in serum (e) cirrhosis (f) he
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effects of VK2809 compared to placebo on liver fat content (assessed by MRI-PDFF, Magnetic Resonance Imaging- Proton Density Fat Fraction).;Secondary Objective: 1. To evaluate the effects of VK2809 compared to placebo on histologic changes assessed by hepatic biopsy. 2. To assess the safety and tolerability of VK2809 administered for 52 weeks.;Primary end point(s): 1. Relative change in liver fat content (assessed by MRI-PDFF) from baseline to Week 12 in subjects treated with VK2809 compared to the change in subjects treated with placebo. ;Timepoint(s) of evaluation of this end point: baseline to Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Absolute change in liver fat content (assessed by MRI-PDFF) from baseline to Week 52 in subjects treated with VK2809 compared to the change in subjects treated with placebo. 2. Relative change in liver fat content (assessed by MRI-PDFF) from baseline to Week 52 in subjects treated with VK2809 compared to the change in subjects treated with placebo. 3. Proportion of subjects with a relative percent decrease in liver fat content = 30% (assessed by MRI-PDFF) from baseline to Week 12 and Week 52 in subjects treated with VK2809 compared to the change in subjects treated with placebo. 4. Proportion of subjects with normalization of liver fat (assessed by MRI-PDFF and defined as a fat fraction of 5% in liver fat content (assessed by MRI-PDFF) from baseline to Week 12 and Week 52 in subjects treated with VK2809 compared to the change in subjects treated with placebo. The following secondary endpoints compare central reader scored histopathologic assessments (liver biopsies) from baseline to Week 52 for subjects treated with VK2809 to responses for subjects treated with placebo. 6. Proportion of subjects with resolution of steatohepatitis on overall histpathological reading and no worsening of liver fibrosis on NASH CRN fibrosis score. Resolution of steatohepatitis is defined as absent fatty liver disease or isolated or simple steatosis without steatohepatitis and a NAS score of 0-1 for inflammation, 0 for ballooning, and any value for steatosis. 7. Proportion of subjects with improvement in liver fibrosis greater than or equal to one stage (NASH CRN fibrosis score) and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis). 8. Proportion of subjects with = 2-point improvement in NAS (with at least 1-point improvement in ballooning or inflammation) with no worsening of fibrosis stage. 9. Proportion of subjects with resolution of steatohepatitis and improvement in fibrosis | — |
Countries
Belgium, France, Mexico, United States
Contacts
Public ContactClinical Operations Department
VIKING THERAPEUTICS, INC.
Outcome results
None listed