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

NCT03432260 | Completed Phase 2 Results FDA Drug

• 1 other identifier: C928-010
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 7

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).

Conditions

Alcoholic Hepatitis

Keywords

Alcoholic Hepatitis; acute alcoholic liver disease; progressive inflammatory liver injury; IV infusion

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (4)

• Serum Cytokeratin 18 (M30)

  Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28

• Serum Cytokeratin 18 (M65)

  Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28

• International Normalized Ratio (INR) - Percent Change From Baseline

  Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28

• Bilirubin - Percent Change From Baseline

  Baseline (Screening or Day 1 Pre-dose), Day 7, Day 28

Other Outcomes (1)

• Serum Creatinine (sCR)

  Baseline (Screening or Day 1 Pre-dose)

Study Arms (6)

Part A (Moderate AH) DUR-928 30 mg

EXPERIMENTAL

Lowest dose of 3 dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 30 mg

Part A (Moderate AH) DUR-928 90 mg

EXPERIMENTAL

Middle dose of 3 dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 90 mg

Part A (Moderate AH) DUR-928 150 mg

EXPERIMENTAL

Highest dose of dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 150 mg

Part B (Severe AH) DUR-928 30 mg

EXPERIMENTAL

Lowest dose of dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 30 mg

Part B (Severe AH) DUR-928 90 mg

EXPERIMENTAL

Middle dose of dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 90 mg

Part B (Severe AH) DUR-928 150 mg

EXPERIMENTAL

Highest dose of dose escalation arms: 30mg, 90 mg and 150 mg

Drug: DUR-928 150 mg

Interventions

DUR-928 30 mg DRUG

Lowest dose of 3 dose escalation arms.

Part A (Moderate AH) DUR-928 30 mg; Part B (Severe AH) DUR-928 30 mg

DUR-928 90 mg DRUG

Middle dose of 3 dose escalation arms.

Part A (Moderate AH) DUR-928 90 mg; Part B (Severe AH) DUR-928 90 mg

DUR-928 150 mg DRUG

Highest dose of 3 dose escalation arms.

Part A (Moderate AH) DUR-928 150 mg; Part B (Severe AH) DUR-928 150 mg

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent (either from patient or patient's legally acceptable representative)
• Male or female patients 21 years of age or older with BMI ≥ 20 to ≤ 40 kg/m2
• Patients with alcoholic hepatitis defined as:
• History of heavy alcohol abuse: \> 40 g/day in females or \> 60 g/day in males for a minimum period of 6 months, AND
• Consumed alcohol within 12 weeks of entry into the study, AND
• Serum bilirubin \> 3 mg/dL AND AST \> ALT, but less than 300 U/L AND
• MELD score between 11-30, inclusive
• No evidence of active infection as determined by the investigator.
• Women of child-bearing potential must utilize appropriate birth control throughout the study duration.
• Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration

You may not qualify if:

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

Sponsors & Collaborators

• Durect: lead
• CTI Clinical Trial and Consulting Services: collaborator

Study Sites (7)

DURECT Study Site 0001

San Diego, California, 92118, United States

Location

DURECT Study Site 007

Miami, Florida, 33136, United States

Location

DURECT Study Site 0004

Atlanta, Georgia, 30309, United States

Location

DURECT Study Site 0002

Chicago, Illinois, 60611, United States

Location

DURECT Study Site 008

Indianapolis, Indiana, 46202, United States

Location

DURECT Study Site 0005

Louisville, Kentucky, 40202, United States

Location

DURECT Study Site 006

San Antonio, Texas, 78215, United States

Location

Related Publications (1)

• Hassanein T, McClain CJ, Vatsalya V, Stein LL, Flamm SL, Martin P, Cave MC, Mitchell M Jr, Barton B, Nagy L, Szabo G, McCullough A, Dasarathy S, Shah J, Blevins C, Scott D, Krebs W, Brown JE, Lin W. Safety, Pharmacokinetics, and Efficacy Signals of Larsucosterol (DUR-928) in Alcohol-Associated Hepatitis. Am J Gastroenterol. 2024 Jan 1;119(1):107-115. doi: 10.14309/ajg.0000000000002275. Epub 2023 Apr 3.

  PMID: 37011138 DERIVED

MeSH Terms

Conditions

Hepatitis, Alcoholic

Condition Hierarchy (Ancestors)

Hepatitis; Liver Diseases; Digestive System Diseases; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Results Point of Contact

• Title: Director of Regulatory Affairs
• Organization: DURECT Corporation

jill.burns@durect.com

408-777-1418

Study Officials

• Robert Gordon, MD

  CTI Clinical Trial and Consulting Services

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Staggered parallel design.

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 14, 2018
• Study Start: April 18, 2018
• Primary Completion: September 9, 2019
• Study Completion: September 9, 2019
• Last Updated: September 24, 2024
• Results First Posted: December 14, 2022

Record last verified: 2022-11

Locations

US (7)