Overview
Rivus Pharmaceuticals. Inc. is sponsoring this research study to assess the safety and tolerability of HU6 as a possible treatment for patients diagnosed with metabolic dysfunction-associated steatohepatitis (MASH). The study will also assess safety, pharmacokinetics (PK) and changes in liver fat content related to patients diagnosed with MASH.
Description
This is a 2-part randomized, double-blind, placebo-controlled, multicenter trial with an open label extension (OLE) to evaluate the safety and exposure of HU6 as well as the effect of HU6 on liver fat and other symptoms associated with MASH.
The 2-part trial design consists of a blinded intervention period and, for participants who completed the blinded intervention period, an option to continue in an OLE intervention period. The blinded trial design consists of a screening period, a blinded intervention period, an end of treatment (EOT)/early termination (ET) visit, a safety follow-up visit, and two long-term follow up visits.
Eligibility
Inclusion Criteria:
- Male and female ≥30 years of age at time of signing the informed consent.
- Diagnosed with metabolic dysfunction-associated steatohepatitis (MASH)
- Women of childbearing potential must not be pregnant or breastfeeding and must use and agree to continue to use a highly effective contraceptive method throughout time on study.
- Body Mass Index (BMI) ≥27.0 kg/m2 to ≤44 kg/m2
Exclusion Criteria:
- Have acute or chronic hepatitis, signs, and symptoms of any other liver disease (eg, Wilson's disease) other than MASH
- Cholecystectomy or any other surgical or medical condition or history that may potentially alter the absorption, metabolism, or excretion of study treatment.
- History (including any family history) of malignant hyperthermia.
- History of malignancy within 5 years (except cutaneous basal or squamous cell carcinoma, carcinoma-in-situ, or low-grade prostate cancer).
- History of the following cardiovascular conditions within 3 months prior to randomization: acute myocardial infarction, cerebrovascular accident (stroke), unstable angina, hospitalization due to congestive heart failure (CHF), or acute CHF.
- Significant and unstable lung disease (chronic obstructive pulmonary disease \[COPD\], emphysema, pulmonary fibrosis, or asthma) requiring oxygen or chronic daily medication. Note that mild, stable COPD and asthma on inhalers are allowed.
- Monogenetic diabetes or type 1 diabetes.
- History of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to Screening.
- History of agranulocytosis.
- History of or active evidence of ophthalmological conditions
- Untreated, uncontrolled, or unstable hypertension
- Use of any of the following medications/therapies: Vitamin E: use of ursodiol or high-dose vitamin E (\>400 IU/day) for a duration of \>1 month within 6 months or started high dose vitamin E for any duration within 3 months prior to screening
- Within 3 months prior to screening or plan to use prior to coming off study drug: resmetirom (Rezdiffra®), GLP 1 agonists and gastric inhibitory polypeptide (GIP)/GLP-1 agonists, Weight loss medications/therapies including: herbal preparation, over the counter (OTC) drug, mail order or prescription drug, Oral antidiabetic medications/therapies including: insulin, meglitinides, thiazolidinediones. Prescription or OTC stimulants. Recent or current use of obeticholic acid (Ocaliva®), systemic corticosteroids, methotrexate, tamoxifen, amiodarone, or long-term use of tetracyclines. Warfarin, heparin, factor Xa inhibitors due to risk of bleeding, Medications with high risk of idiosyncratic drug-induced neutropenia (IDIN) or agranulocytosis.
- History of hepatitis or human immunodeficiency virus (HIV1 \& HIV2)
- Intolerance to MRI or with conditions contraindicated for MRI procedures
- Participation in another clinical trial at the time of screening or exposure to any investigational product, including topical agents, within 28 days prior to starting study treatment
- Additional inclusion/exclusion criteria could apply