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

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.

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

Study Overview

• Status: Terminated
• Conditions: Severe Acute Decompensated Alcoholic Hepatitis
• Intervention / Treatment: Drug: 1000mg DS102 (BID)

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Batumi, Georgia
    • Batumi Referral Hospital
  • Kutaisi, Georgia
    • Saint Nikolozi Surgery Center
• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases (University Hospital Miami)
    • Miami, Florida, United States, 33331
      • Cleveland Clinic Florida
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Kansas University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Afimmune
• Investigators: Principal Investigator: Mark Thursz, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2018
• Primary Completion (Actual): June 19, 2019
• Study Completion (Actual): March 31, 2020

Study Registration Dates

• First Submitted: February 26, 2018
• First Submitted That Met QC Criteria: February 26, 2018
• First Posted (Actual): March 2, 2018

Study Record Updates

• Last Update Posted (Actual): July 29, 2022
• Last Update Submitted That Met QC Criteria: July 5, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Hepatitis; Hepatitis A; Hepatitis, Alcoholic
• Other Study ID Numbers: DS102A-05-AH1; 2018-000819-25 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No