MRG-001 in Patients With Alcoholic Hepatitis

Официальное название

An Open-Label, Dose-Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of MRG-001 in Patients With Alcoholic Hepatitis

Обзор

The goal of this study is to test MRG-001 (an experimental medication). The purpose of this trial is to assess the dose related safety, Pharmacokinetics, and Pharmacodynamics of MRG-001 in patients with severe alcoholic hepatitis (AH).

Вмешательства

• Препарат MRG-001
  Patients will receive subcutaneous administration of MRG-001 at designated visits.

Первичные конечные точки

• Assessment of Treatment-Emergent Adverse Events [Срок оценки: 28 Days]

Вторичные конечные точки (2)

• Pharmacokinetic Response [Срок оценки: 28 Days]
• Pharmacodynamic Response [Срок оценки: 28 Days]

Критерии участия

Критерии включения

• Informed Consent: Able to provide written informed consent, either personally or through a legally acceptable representative.
• Male or female patients 21 years of age or older.
• Onset of jaundice within the prior 8 weeks.
• Alcohol Consumption: Average daily consumption of more than 40 grams for females or more than 60 grams for males of alcohol for 6 months or longer, with less than 8 weeks of abstinence before the onset of jaundice.
• Diagnostic Criteria for AH: AH may be diagnosed based on typical serum chemistry or liver biopsy during the current episode of AH, including:

• Serum bilirubin > 3 mg/dL
• AST between 50 and 400 IU/L
• ALT < 400 IU/L
• AST/ALT ratio > 1.5
• Maddrey Discriminant Function (MDF): MDF ≥ 32, assuming a control prothrombin time of 12 seconds.
• Model for End-stage Liver Disease (MELD) Score: MELD score between 21 and 30.
• Liver Biopsy (Optional): Liver biopsy is not required but may be used to confirm the diagnosis of AH at the Investigator's discretion. If used, the biopsy must have occurred during the current episode.
• Contraception for Women: Women of childbearing potential must use appropriate birth control throughout the study duration. Contraception for Men: Male patients must agree to use a medically acceptable method of contraception or birth control throughout the study duration.

Критерии исключения

• Informed Consent: Inability to provide written informed consent, either personally or through a legally acceptable representative.
• Participation in Other Clinical Trials: Participation in another interventional clinical trial (drug or device) within 30 days of screening and at any time during the study.
• Concomitant Liver Diseases: Presence of other concomitant causes of liver disease, such as viral hepatitis, autoimmune liver disease, metabolic liver disease, or vascular liver disease.
• Liver Biopsy Incompatibility: Liver biopsy findings, if conducted, not compatible with alcoholic hepatitis (AH).
• Absence of Active Infection: No evidence of active infection as determined by the investigator, with specific criteria outlined for diagnosing and treating infections.
• Uncontrolled Gastrointestinal Bleeding: Presence of uncontrolled gastrointestinal bleeding.
• History of pre-admission refractory ascites, as defined by the frequency of paracenteses despite diuretic therapy.
• Significant pre-existing organ dysfunction in various systems, including lung, heart, kidney, hematologic, neurological, and spleen-related conditions.

• Lung: Receiving supplemental home oxygen therapy at baseline for pre-existing medical condition (other than COVID-19), as documented in medical record.
• Heart: Pre-existing congestive heart failure defined as an ejection fraction <20% as documented in the medical record. Clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation), unstable angina, myocardial infarction (past 3 months), heart and coronary vessel surgery (past 3 months), significant valvular heart disease, uncontrolled arterial hypertension with systolic blood pressure >180 mm Hg and diastolic blood pressure >110 mm Hg.
• Renal: End-stage renal disease requiring renal replacement therapy or creatintine clearance <30 mL/min.
• Hematologic: Baseline platelet count <30,000/mm3 or hemoglobin levels <6.0 g/dL.
• Neurological: Stage ≥3 hepatic encephalopathy by West Haven criteria.
• History of splenectomy or splenomegaly (spleen weighing > 750 g).
• Presence of any active malignancy or malignancy diagnosed within the last five years, excluding curable skin cancer.
• Patients requiring the use of vasopressors or inotropic support, excluding stabilized conditions within the first 7 days of hospital admission.
• Presence of co-infection with human immunodeficiency virus (HIV) or active tuberculosis on chest X-ray at study entry.
• History of organ or bone marrow transplantation, excluding corneal transplant, or recent chronic use of immunosuppressive drugs.
• Positive urine drug screen for specific substances, excluding THC and prescription medications.
• Hypersensitivity to either of the components of MRG-001.
• If female, known pregnancy, positive serum pregnancy test, or lactating/breastfeeding.
• Underlying diseases that might be complicated or exacerbated by proposed treatments or confound assessment of study drug, as determined by the site investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Ahmadi AR, Atiee G, Chapman B, Reynolds L, Sun J, Cameron AM, Wesson RN, Burdick JF, Sun Z. A phase I, first-in-human study to evaluate the safety and tolerability, pharmacokinetics, and pharmacodynamics of MRG-001 in healthy subjects. Cell Rep Med. 2023 Sep 19;4(9):101169. doi: 10.1016/j.xcrm.2023.101169. Epub 2023 Aug 25. PMID 37633275

Идентификаторы

NCT: NCT06307522 · MRG24ALC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗