Severe Acute Decompensated Alcoholic Hepatitis Clinical Trial
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.
| Verified date | July 2022 |
| Source | Afimmune |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Terminated |
| Enrollment | 9 |
| Est. completion date | March 31, 2020 |
| Est. primary completion date | June 19, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Georgia | Batumi Referral Hospital | Batumi | |
| Georgia | Saint Nikolozi Surgery Center | Kutaisi | |
| United States | Beth Israel Deaconess Medical Center | Boston | Massachusetts |
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | Kansas University Medical Center | Kansas City | Kansas |
| United States | Cleveland Clinic Florida | Miami | Florida |
| United States | Schiff Center for Liver Diseases (University Hospital Miami) | Miami | Florida |
| United States | Bon Secours Liver Institute of Richmond and Bon Secours Liver Institute of Hampton Roads | Newport News | Virginia |
| Lead Sponsor | Collaborator |
|---|---|
| Afimmune |
United States, Georgia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | |
| Primary | 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 |