A Phase II Study to Assess the Efficacy and Safety of Orally Administered DS102 in Patients with Severe Acute Decompensated Alcoholic Hepatitis.
- Conditions
- Severe Acute Decompensated Alcoholic HepatitisTherapeutic area: Diseases [C] - Digestive System Diseases [C06]MedDRA version: 20.0 Level: LLT Classification code 10001624 Term: Alcoholic hepatitis System Organ Class: 100000004871
- Registration Number
- EUCTR2018-000819-25-LV
- Lead Sponsor
- Afimmune
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 126
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. Aspartate aminotransferase/alanine aminotransferase
(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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 101
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25
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:
a. Evidence of chronic viral hepatitis (Hepatitis B DNA positive or HCV RNA positive).
b. Biliary obstruction.
c. Hepatocellular carcinoma.
d. Wilsons disease.
e. Budd Chiari Syndrome.
f. 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 oromega-6 fatty acids in the four weeks prior to baseline.
14. Patients dependent on inotropic support (adrenaline or noradrenaline), including Terlipressin.
15. Active variceal hemorrhage on this admission requiring more than 2 units of blood to maintain hemoglobin level within 48 hours
16. Presence of refractory ascites.
17. Untreated or unresolved sepsis.
18. Patients with cerebral hemorrhage, extensive retinal hemorrhage, 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 & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: Efficacy Objective:<br> • To compare the efficacy of orally administered DS102 capsules versus placebo, in the treatment of adult patients with severe acute decompensated Alcoholic Hepatitis (AH).<br> Safety Objective:<br> • To compare the safety of orally administered DS102 capsules versus placebo, in the treatment of adult patients with severe acute decompensated AH.<br> Pharmacokinetic Objective:<br> • To evaluate the pharmacokinetics (PK) of 15(S)-HEPE following orally administered DS102 capsules, in six adult patients with AH in the initial pilot phase of the study, followed by trough level assessment of 15(S)-HEPE in all study participants.<br> ;Secondary Objective: N/A;Primary end point(s): • Percentage change in MELD score from baseline to Day 28;Timepoint(s) of evaluation of this end point: From Baseline to Day 28
- Secondary Outcome Measures
Name Time Method