A 6-Month, Randomized, Double-Blind, Placebo-controlled, Phase 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis
Overview
- Phase
- Phase 2
- Intervention
- HU6
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Sponsor
- Rivus Pharmaceuticals, Inc.
- Enrollment
- 219
- Locations
- 20
- Primary Endpoint
- Percent change from baseline in liver fat, as assessed by magnetic resonance imaging liver proton density fat fraction (MRI-Liver PDFF) at 6 months (26 weeks)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase 2 randomized, double-blind, placebo-controlled parallel group study of 3 dose levels of HU6 in subjects with nonalcoholic steatohepatitis (NASH). Six months (26 weeks) of dosing is planned, and subjects will be followed for safety, efficacy, pharmacodynamics (PD), and pharmacokinetics (PK) during this time. The end-of-study visit will take place approximately 4 weeks after the last dose of the study drug (Week 30).
Detailed Description
This is a phase 2 randomized, double-blind, placebo-controlled parallel group study of 3 dose levels of HU6 (150 mg, 300 mg, and 450 mg) and placebo in approximately 204 subjects with NASH. Subjects will be screened over a 49-day period to determine their eligibility based on specific history, physical, laboratory, and imaging evaluations, which will require more than one visit during the screening period. On Day 1, subjects will be randomized 2:1:2:2 into 1 of 4 treatment groups (placebo, 150 mg HU6, 300 mg HU6, or 450 mg HU6). Six months (26 weeks) of dosing is planned, and subjects will be followed for safety, efficacy, PD, and PK during this time. The end-of-study visit will take place approximately 4 weeks after the last dose of the study drug (Week 30).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Able to understand the procedures and requirements of the study and provide written informed consent and authorization for protected health information disclosure.
- •Willing and able to comply with the requirements of the study protocol.
- •Male or female ≥18 years of age at time of informed consent.
- •Subject has a screening Fibroscan® CAP score \>306 decibels per meter (dB/m) and interquartile range to median ratio (IQR/Med) \<30%.
- •Subject has ≥8% liver fat determined by screening Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF).
- •Subject has moderate to advanced liver fibrosis based on documented history of biopsy score of F2 or F3 within 12 months prior to Screening, or subject has a screening Fibroscan® vibration-controlled transient elastography (VCTE) score ≥ 7.0 to ≤ 15.0 kPa.
- •Body mass index (BMI) ≥27.0 kg/m
- •Clinically euthyroid as assessed by a thyroid profile utilizing TSH and T4 testing at screening as assessed by the investigator based on the medical history of the subject.
- •Subjects with a diagnosis of glaucoma must be controlled and stable (no changes in treatment regimen within 3 months prior to Screening).
- •Inclusion as per investigator assessment of general medical status and as documented by medical history, physical examination, vital sign assessments, 12-lead ECG, clinical laboratory assessments, and general observations.
Exclusion Criteria
- •Subjects will be excluded from the study if any of the following criteria are met:
- •The subject has a history of cirrhosis and/or hepatic decompensation, including ascites, hepatic encephalopathy, or variceal bleeding.
- •The subject has a history of acute pancreatitis within 1 year of Screening or chronic pancreatitis of any cause.
- •History of any bariatric surgery intervention, including but not limited to lap banding, intragastric balloon, duodenal-jejunal sleeve, or bariatric surgery or plans for bariatric surgery prior to conclusion of study participation.
- •Have obesity induced by other endocrinologic disorders (e.g., Cushing Syndrome, polycystic ovarian syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome).
- •Any surgical or medical condition or history that, in the opinion of the investigator in consultation with the medical monitor, may potentially alter the absorption, metabolism, or excretion of study treatment.
- •History of or treatment for clinically significant gastroparesis, inflammatory bowel disease, or any surgery of the upper gastrointestinal tract with the exception of cholecystectomy, or minor gastric procedures that are approved by the medical monitor.
- •History (including any family history) of malignant hyperthermia.
- •History of chronic serious recurrent skin rashes of unknown cause.
- •History of malignancy within 5 years (except cutaneous basal or squamous cell carcinoma, carcinoma-in-situ, or low-grade prostate cancer).
Arms & Interventions
Active Treatment: HU6 Planned doses of HU6
Intervention: HU6
Placebo Comparator Non-active study drug
Intervention: Placebo
Outcomes
Primary Outcomes
Percent change from baseline in liver fat, as assessed by magnetic resonance imaging liver proton density fat fraction (MRI-Liver PDFF) at 6 months (26 weeks)
Time Frame: 6 months