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

Phase 2

Terminated

Conditions: Severe Acute Decompensated Alcoholic Hepatitis

Interventions: Drug: 1000mg DS102 (BID)

Registration Number: NCT03452540

Lead Sponsor: Afimmune

Brief 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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 9

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:
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
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1000mg DS102 (BID)	1000mg DS102 (BID)	Participants assigned to the open label pilot phase received 1000mg DS102 (BID)for 28 days.

Primary Outcome Measures

Name	Time	Method
Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs.	Up to 28 days.	To evaluate the safety of orally administered DS102 in the treatment of adult patients with severe acute decompensated AH.
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	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.

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (8): Cleveland Clinic Florida
🇺🇸
Miami, Florida, United States
Kansas University Medical Center
🇺🇸
Kansas City, Kansas, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States
Schiff Center for Liver Diseases (University Hospital Miami)
🇺🇸
Miami, Florida, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Saint Nikolozi Surgery Center
🇬🇪
Kutaisi, Georgia
Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads
🇺🇸
Newport News, Virginia, United States
Batumi Referral Hospital
🇬🇪
Batumi, Georgia