Company Decision

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

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

The Full Analysis Set (FAS) included all patients who received at least one dose of investigational product. Patients were analysed according to the treatment they were assigned to, irrespective of what treatment they actually received.

Up to 90 days.

An adverse event is any undesirable experience occurring to a patient that has signed the ICF and who has taken their first dose of the study drug, whether or not considered related to the investigational medicinal product (IMP). All Adverse Events (AEs) were recorded in the CRF, defining relationship to IMP and severity.

Early termination - The study was stopped at the end of the pilot phase (n=9) as the sponsor prioritised other therapeutic indications, so no patients were enrolled in the double-blind phase.