Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis

Study Overview
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Brief Summary
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The purpose of this randomised, double-blind, placebo-controlled, phase II study is to assess the efficacy and safety of orally administered DS102 in adult patients with acute decompensated alcoholic hepatitis

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Phase II Study to Assess the Efficacy and Safety of Orally Administered DS102 in Patients With Acute Decompensated Alcoholic Hepatitis.

Conditions
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Severe Acute Decompensated Alcoholic Hepatitis

Intervention / Treatment
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* Drug: 1000mg DS102 (BID)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 18 years and older Total bilirubin of ≥ 5 mg/dl (85μmol/l) Patients with definite or probable AH MELD ≥18 at baseline visit MDF ≥32 at baseline visit AST ≥50 U/L AST':ALT ratio > 1.5 Female patients, or female partners of male patients, of child bearing potential must use highly effective birth control methods or have a sterilised partner for the duration of the study. Highly effective birth control methods are defined as methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include intrauterine device or sexual abstinence. Note: A woman is considered of child bearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy Note: Hormonal contraceptives are contraindicated in patients with severe hepatic diseases and are not acceptable as a birth control method in this study Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject Patient and/or legally authorised representative must provide informed consent Able to swallow the provided study medication Not eligible for liver transplant during this hospitalisation Exclusion Criteria: Pregnant or lactating females. Spontaneous liver function improvement defined by decrease of bilirubin level and MDF of >10% within 5 days of hospital admission Grade 4 hepatic encephalopathy (West Haven Criteria) Type 1 hepatorenal syndrome (HRS) or a serum creatinine >2 x ULN or the requirement for haemodialysis History of hypersensitivity to any substance in DS102 capsules or placebo capsules. Alcohol abstinence of >6 weeks prior to screening Duration of clinically apparent jaundice >3 months prior to baseline Other causes of liver disease including: Evidence of chronic viral hepatitis (Hepatitis B DNA positive or HCV RNA positive) Biliary obstruction Hepatocellular carcinoma Wilsons disease Budd Chiari Syndrome Non-alcoholic fatty liver disease History of or active non-liver malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas). Previous entry into the study AST >400 U/L or ALT >270 U/L Treatment with any experimental drug within 30 days prior to Day 0 visit (Baseline), or 5 half-lives (whichever is longer). Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in the four weeks prior to baseline. Patients dependent on inotropic support (adrenaline or noradrenaline), including Terlipressin Active variceal haemorrhage on this admission requiring more than 2 units of blood to maintain haemoglobin level within 48 hours Presence of refractory ascites Untreated or unresolved sepsis Patients with cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial infarction (within last 6 weeks) or severe cardiac arrhythmias (not including atrial fibrillation) Known infection with HIV at screening. Significant systemic or major illnesses other than liver disease that, in the opinion of the investigator, would preclude or interfere with treatment with DS102 and/or adequate follow up. Previous liver transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1000mg DS102 (BID)<br>Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days. | Drug: 1000mg DS102 (BID)<br>* Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs. | To evaluate the safety of orally administered DS102 in the treatment of adult patients with severe acute decompensated AH. | Up to 28 days. | 
| Descriptive Statistics for Plasma Total 15(S)-HEPE and Unesterified 15(S)-HEPE Pharmacokinetic Results for 1000 mg BD DS102 Administered Orally Twice-daily to Patients With Alcoholic Hepatitis | Descriptive Statistics for Plasma Total 15(S)-HEPE and Unesterified 15(S)-HEPE Pharmacokinetic Results for 1000 mg BD DS102 Administered Orally Twice-daily to Patients with Alcoholic Hepatitis. | Up to 7 days |