Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis
Condition: Severe Acute Decompensated Alcoholic Hepatitis
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Intervention: 1000mg DS102 (BID)
Intervention description: Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients aged 18 years and older

          2. Total bilirubin of ≥ 5 mg/dl (85μmol/l)

          3. Patients with definite or probable AH

          4. MELD ≥18 at baseline visit

          5. MDF ≥32 at baseline visit

          6. AST ≥50 U/L

          7. AST':ALT ratio > 1.5

          8. 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

          9. Patient and/or legally authorised representative must provide informed consent

         10. Able to swallow the provided study medication

         11. Not eligible for liver transplant during this hospitalisation

        Exclusion Criteria:

          1. Pregnant or lactating females.

          2. Spontaneous liver function improvement defined by decrease of bilirubin level and MDF
             of >10% within 5 days of hospital admission

          3. Grade 4 hepatic encephalopathy (West Haven Criteria)

          4. Type 1 hepatorenal syndrome (HRS) or a serum creatinine >2 x ULN or the requirement
             for haemodialysis

          5. History of hypersensitivity to any substance in DS102 capsules or placebo capsules.

          6. Alcohol abstinence of >6 weeks prior to screening

          7. Duration of clinically apparent jaundice >3 months prior to baseline

          8. Other causes of liver disease including:

               1. Evidence of chronic viral hepatitis (Hepatitis B DNA positive or HCV RNA
                  positive)

               2. Biliary obstruction

               3. Hepatocellular carcinoma

               4. Wilsons disease

               5. Budd Chiari Syndrome

               6. Non-alcoholic fatty liver disease

          9. History of or active non-liver malignancies other than curatively treated skin cancer
             (basal cell or squamous cell carcinomas).

         10. Previous entry into the study

         11. AST >400 U/L or ALT >270 U/L

         12. Treatment with any experimental drug within 30 days prior to Day 0 visit (Baseline),
             or 5 half-lives (whichever is longer).

         13. Patients who have used dietary supplements rich in omega-3 or omega-6 fatty acids in
             the four weeks prior to baseline.

         14. Patients dependent on inotropic support (adrenaline or noradrenaline), including
             Terlipressin

         15. Active variceal haemorrhage on this admission requiring more than 2 units of blood to
             maintain haemoglobin level within 48 hours

         16. Presence of refractory ascites

         17. Untreated or unresolved sepsis

         18. Patients with cerebral haemorrhage, extensive retinal haemorrhage, acute myocardial
             infarction (within last 6 weeks) or severe cardiac arrhythmias (not including atrial
             fibrillation)

         19. Known infection with HIV at screening.

         20. 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.

         21. Previous liver transplantation