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

• ClinicalTrials.gov Identifier: NCT03452540
• Recruitment Status: Terminated
• First Posted: March 2, 2018
• Results First Posted: July 29, 2022
• Last Update Posted: July 29, 2022
• Sponsor: Afimmune
• Information provided by (Responsible Party): Afimmune

Study Description

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

Condition or disease	Intervention/treatment	Phase
Severe Acute Decompensated Alcoholic Hepatitis	Drug: 1000mg DS102 (BID)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 9 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: November 28, 2018
• Actual Primary Completion Date: June 19, 2019
• Actual Study Completion Date: March 31, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

Schiff Center for Liver Diseases (University Hospital Miami)

Miami, Florida, United States, 33136

Cleveland Clinic Florida

Miami, Florida, United States, 33331

United States, Kansas

Kansas University Medical Center

Kansas City, Kansas, United States, 66160

United States, Massachusetts

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States, 02215

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Virginia

Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads

Newport News, Virginia, United States, 23602

Georgia

Batumi Referral Hospital

Batumi, Georgia

Saint Nikolozi Surgery Center

Kutaisi, Georgia

Sponsors and Collaborators

Afimmune

Investigators

• Principal Investigator: Mark Thursz; Imperial College London

  Study Documents (Full-Text)

Documents provided by Afimmune:

Study Protocol  [PDF] November 14, 2018

Statistical Analysis Plan  [PDF] January 25, 2019

More Information

• Responsible Party: Afimmune
• ClinicalTrials.gov Identifier: NCT03452540
• Other Study ID Numbers: DS102A-05-AH1; 2018-000819-25 ( EudraCT Number )
• First Posted: March 2, 2018
• Results First Posted: July 29, 2022
• Last Update Posted: July 29, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hepatitis A; Hepatitis; Hepatitis, Alcoholic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Infections; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders