Clinical trial NCT03452540: Efficacy and Safety of Orally Administered DS102 in Patients With Acute Alcoholic Hepatitis
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Severe Acute Decompensated Alcoholic Hepatitis
Lead sponsor: Afimmune
Sponsor class: INDUSTRY
First posted: 2018-03-02
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Treatment-emergent Adverse Events (TEAEs), Serious TEAEs, and SUSARs.
timeFrame: Up to 28 days.
measure: 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
timeFrame: Up to 7 days
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Schiff Center for Liver Diseases (University Hospital Miami)
state: Florida
city: Miami
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Newport News
country: United States
facility: Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads
state: Virginia
city: Batumi
country: Georgia
facility: Batumi Referral Hospital
city: Kutaisi
country: Georgia
facility: Saint Nikolozi Surgery Center
Study officials:
affiliation: Imperial College London
name: Mark Thursz
role: PRINCIPAL_INVESTIGATOR
References: