Clinical trial NCT03432260: A Research Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of DUR-928 in Patients With Alcoholic Hepatitis
Official title: An Open- Label, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Signals of DUR-928 in Patients With Alcoholic Hepatitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis
acute alcoholic liver disease
progressive inflammatory liver injury
IV infusion
Lead sponsor: Durect
Sponsor class: INDUSTRY
Collaborators: name: CTI Clinical Trial and Consulting Services
First posted: 2018-02-14
Enrollment: 19
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Staggered parallel design.
Primary purpose: TREATMENT

Brief summary: This is a research trial testing DUR-928 (an experimental medication). The purpose of this trial is to assess the dose related safety, Pharmacokinetics, and Pharmacodynamics of DUR 928 in patients with moderate and severe alcoholic hepatitis (AH).


Eligibility criteria: Inclusion Criteria:

1. Able to provide written informed consent (either from patient or patient's legally acceptable representative)
2. Male or female patients 21 years of age or older with BMI ≥ 20 to ≤ 40 kg/m2
3. Patients with alcoholic hepatitis defined as:

   1. History of heavy alcohol abuse: \> 40 g/day in females or \> 60 g/day in males for a minimum period of 6 months, AND
   2. Consumed alcohol within 12 weeks of entry into the study, AND
   3. Serum bilirubin \> 3 mg/dL AND AST \> ALT, but less than 300 U/L AND
   4. MELD score between 11-30, inclusive
4. No evidence of active infection as determined by the investigator.
5. Women of child-bearing potential must utilize appropriate birth control throughout the study duration.
6. Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration

Exclusion Criteria:

1. Other or concomitant cause(s) of liver disease as a result of:

   1. Autoimmune liver disease
   2. Wilson disease
   3. Vascular liver disease
   4. Drug induced liver disease
2. Co-infection with human immunodeficiency virus (HIV) or Hepatitis B
3. Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas)
4. If female, known pregnancy, or has a positive serum pregnancy test, or lactating/breastfeeding
5. Serum creatinine \> 2.5 mg/dL
6. Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant
7. Stage 3 or greater encephalopathy by West Haven criteria

Primary outcomes:
measure: Lille Model for Alcoholic Hepatitis Score
timeFrame: Day 7
measure: Model for End Stage Liver Disease (MELD) Score
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
measure: Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
Secondary outcomes:
measure: Serum Cytokeratin 18 (M30)
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
measure: Serum Cytokeratin 18 (M65)
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
measure: International Normalized Ratio (INR) - Percent Change From Baseline
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
measure: Bilirubin - Percent Change From Baseline
timeFrame: Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Other outcomes:
measure: Serum Creatinine (sCR)
timeFrame: Baseline (Screening or Day 1 Pre-dose)
Locations:
city: San Diego
country: United States
facility: DURECT Study Site 0001
state: California
city: Miami
country: United States
facility: DURECT Study Site 007
state: Florida
city: Atlanta
country: United States
facility: DURECT Study Site 0004
state: Georgia
city: Chicago
country: United States
facility: DURECT Study Site 0002
state: Illinois
city: Indianapolis
country: United States
facility: DURECT Study Site 008
state: Indiana
city: Louisville
country: United States
facility: DURECT Study Site 0005
state: Kentucky
city: San Antonio
country: United States
facility: DURECT Study Site 006
state: Texas
Study officials:
affiliation: CTI Clinical Trial and Consulting Services
name: Robert Gordon, MD
role: STUDY_DIRECTOR
References: