A Parallel Treatment Group, Phase 2a, Double-blind, 4-arm Trial to Evaluate the Safety, Exposure, and Efficacy of HU6 Compared With Placebo in Male and Female Participants Aged 30 Years or Older With Metabolic Dysfunction-associated Steatohepatitis (MASH)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 31
- 主要终点
- Drug elimination half-life (t½)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Placebo Once Daily
Placebo Once Daily (QD)
干预措施: Placebo (Other)
HU6 450 mg
450 mg Once Daily (QD)
干预措施: HU6 (Drug)
HU6 300 mg
300 mg Twice Daily (BID)
干预措施: HU6 (Drug)
Placebo Twice Daily
Placebo Twice Daily (BID)
干预措施: Placebo (Other)
结局指标
主要结局
Drug elimination half-life (t½)
时间窗: 26 weeks
Area Under the Plasma Concentration-Time Curve (AUC)
时间窗: 26 weeks
Trough Plasma Concentration (Ctrough)
时间窗: 26 weeks
Maximum Observed Plasma Concentration (Cmax)
时间窗: 26 weeks
Time to Maximum Plasma Concentration (Tmax)
时间窗: 26 weeks
Volume of distribution after extravascular administration (V/F)
时间窗: 26 weeks
Plasma Clearance of drug after extravascular administration (CL/F)
时间窗: 26 weeks
Number and Percentage of Adverse Events (AEs)
时间窗: 26 weeks
Percent change from baseline to Week 26 In Liver Fat Assessed by MRI-PDFF
时间窗: 26 weeks
Percentage of participants with Liver Fat reduction by ≥30% Assessed by MRI-PDFF
时间窗: 26 weeks
次要结局
未报告次要终点