A Research Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of DUR-928 in Patients With Alcoholic Hepatitis

Alcoholic Hepatitis Clinical Trial

— AH  

Official title:

An Open- Label, Dose Escalation Study to Assess the Safety, Pharmacokinetics and Pharmacodynamic Signals of DUR-928 in Patients With Alcoholic Hepatitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03432260
• Other study ID #: C928-010
• Status: Completed
• Phase: Phase 2
• Start date: April 18, 2018
• Est. completion date: September 9, 2019

Study information

• Verified date: November 2022
• Source: Durect
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 9, 2019
• Est. primary completion date: September 9, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alcoholic Hepatitis
• Hepatitis
• Hepatitis A
• Hepatitis, Alcoholic

Intervention

Drug:
• DUR-928 30 mg
Lowest dose of 3 dose escalation arms.
• DUR-928 90 mg
Middle dose of 3 dose escalation arms.
• DUR-928 150 mg
Highest dose of 3 dose escalation arms.

Locations

Country	Name	City	State
United States	DURECT Study Site 0004	Atlanta	Georgia
United States	DURECT Study Site 0002	Chicago	Illinois
United States	DURECT Study Site 008	Indianapolis	Indiana
United States	DURECT Study Site 0005	Louisville	Kentucky
United States	DURECT Study Site 007	Miami	Florida
United States	DURECT Study Site 006	San Antonio	Texas
United States	DURECT Study Site 0001	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Durect	CTI Clinical Trial and Consulting Services

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum Creatinine (sCR)	Serum Creatinine (sCR) at baseline is provided as part of the calculation for MELD	Baseline (Screening or Day 1 Pre-dose)
Primary	Lille Model for Alcoholic Hepatitis Score	The Lille score predicts response of AH subjects to treatment with glucocorticoids, such as prednisolone. This score is based on age, serum albumin, creatinine, PT, and the difference in bilirubin between pre-treatment and Day 7 post-treatment. The Lille score ranges from 0.01 to 1.00. A score >0.45 predicts a higher risk of death and the recommendation to stop steroid administration.; Lille Score = Exp(-R)/(1 + Exp(-R)); Where: R = [3.19 - (0.101 x Age in years)] + (1.47 x Albumin in g/dL) + [0.28215 x (Bilirubin initial - Bilirubin day 7 in mg/dL)] - (0.206 x Creatinine in mg/dL) - (0.11115 x Bilirubin initial in mg/dL) - (0.0096 x PT in seconds) NOTE: When calculating Lille, use "baseline" values for ALL parameters EXCEPT bilirubin at Day 7. Baseline would be the Day 1 Pre-dose sample result, if available. If not available, then use the Screening sample result.	Day 7
Primary	Model for End Stage Liver Disease (MELD) Score	The MELD score at enrollment is a good predictor for AH patient prognosis. Laboratory values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. The MELD score ranges from 6.0 to 40.0 (capped) with a higher score predicting a higher risk of death. A sequentially improving MELD score is associated with a better chance of recovery.; MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level.; Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.	Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
Primary	Model for End Stage Liver Disease (MELD) Score - Percent Change From Baseline	The MELD Score %change from baseline is a %change between 2 time points, baseline and value at a specific time point (Day 7 or Day 28). MELD score is a good predictor of outcome. A declining MELD score suggests disease improvement. Lab values for international normalized ratio (INR), serum creatinine (sCr) and bilirubin are used to calculate the MELD score. MELD score will be calculated using the original formula (pre-2016) which does not include serum sodium level. Original MELD Score = (0.957 x Ln(Serum Creatinine in mg/dL) + 0. 378 x Ln(Serum Bilirubin in mg/dL) + 1.120 x Ln (INR) + 0.643) x 10 Note: (1) If patient received two or more dialysis treatments within the prior 7 days, then the value for serum creatinine will be set to 4.0. (2) If any laboratory value is less than 1.0, the value will be set to 1.0 for the MELD score calculation, in order to avoid negative values resulting from taking the natural log of values less than 1.	Baseline (Screening or Day 1 Pre-dose), Day 7 and Day 28
Secondary	Serum Cytokeratin 18 (M30)	Analysis Population Description: Analysis has been severely delayed due to unavailable testing reagents. Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose.	Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Secondary	Serum Cytokeratin 18 (M65)	Analysis Population Description: Analysis has been severely delayed due to unavailable testing reagents. Baseline was defined as the last non-missing value prior to study drug administration, at Screening or Day 1 Pre-dose.	Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Secondary	International Normalized Ratio (INR) - Percent Change From Baseline	ITT population. INR (international normalized ratio) is a standardized number based on the prothrombin time and calculated by the clinical lab. INR measures the time it takes for blood to clot in vitro and measures, among other things, liver synthetic function.	Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28
Secondary	Bilirubin - Percent Change From Baseline	ITT population	Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28