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History of Changes for Study: NCT04563026
A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (AHFIRM)
Latest version (submitted February 23, 2024) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 18, 2020 None (earliest Version on record)
2 February 1, 2021 Recruitment Status, Study Status and Contacts/Locations
3 March 22, 2021 Contacts/Locations and Study Status
4 May 11, 2021 Contacts/Locations and Study Status
5 June 11, 2021 Contacts/Locations and Study Status
6 July 26, 2021 Contacts/Locations and Study Status
7 October 11, 2021 Contacts/Locations and Study Status
8 December 9, 2021 Contacts/Locations and Study Status
9 January 28, 2022 Contacts/Locations and Study Status
10 March 8, 2022 Contacts/Locations and Study Status
11 May 2, 2022 Contacts/Locations and Study Status
12 June 13, 2022 Study Status
13 August 6, 2022 Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status and Eligibility
14 September 29, 2022 Contacts/Locations and Study Status
15 November 7, 2022 Contacts/Locations and Study Status
16 June 15, 2023 Recruitment Status, Contacts/Locations, Study Status and Study Design
17 February 23, 2024 Recruitment Status, Study Status and Study Design
Comparison Format:

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Changes (Merged) for Study: NCT04563026
June 13, 2022 (v12) -- August 6, 2022 (v13)

Changes in: Study Status, Arms and Interventions, Outcome Measures, Eligibility and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: C928-011
Brief Title: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment (AHFIRM)
Official Title: A Randomized, Double-blind, Placebo-controlled, Phase 2b Study to Evaluate Safety and Efficacy of DUR-928 in Subjects With Alcoholic Hepatitis
Secondary IDs:
Open or close this module Study Status
Record Verification: June 2022 August 2022
Overall Status: Recruiting
Study Start: January 22, 2021
Primary Completion: September 2023 [Anticipated]
Study Completion: September 2023 [Anticipated]
First Submitted: September 18, 2020
First Submitted that
Met QC Criteria:
September 18, 2020
First Posted: September 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
June 13, 2022 August 6, 2022
Last Update Posted: June 14 August 10, 2022 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Durect
Responsible Party: Sponsor
Collaborators: CTI Clinical Trial and Consulting Services
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This is a randomized, double-blind, placebo-controlled, phase 2b clinical Trial evaluating Safety and Efficacy of DUR-928 (an experimental medication) in Patients with Alcoholic Hepatitis (AH).
Detailed Description:
Open or close this module Conditions
Conditions: Alcoholic Hepatitis
Keywords: Alcoholic Hepatitis
acute alcoholic liver disease
progressive inflammatory liver injury
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.
Number of Arms: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 300 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: DUR-928 (larsucosterol, 30 mg) Drug: DUR-928 30 mg
IV infusion
Experimental: DUR-928 (larsucosterol, 90 mg) Drug: DUR-928 90 mg
IV infusion
Placebo Comparator: (Placebo) Sterile Water for Injection Drug: Placebo+ Standard of Care (SOC)
IV infusion
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 90-day mortality between active group/s and placebo (SOC) group Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
[ Time Frame: Day 90 ]

Secondary Outcome Measures:
1 . Occurrence of adverse events or laboratory abnormalities
[ Time Frame: Day 1 to Day 90 ]

Percentage of Participants with Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Laboratory Abnormalities within 90 days of dosing
2 1. Lille score at Day 7 after the initiation of study drug treatment between the treatment groups Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
[ Time Frame: Day 7 90 ]

3 2. MELD score at Day 28 after the initiation of study drug treatment between the treatment groups Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo.
[ Time Frame: Day 28 ]

4 3. 28-day mortality between the treatment groups Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo.
[ Time Frame: Day 28 ]

5 . ICU days at Day 28
[ Time Frame: Day 1 to Day 28 ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Able to provide written informed consent (either from subject or subject's legally acceptable representative).
  2. Onset of jaundice within prior 8 weeks.
  3. Average daily consumption of >40 (females) or >60 (males) grams of alcohol for 6 months or longer, with < 8 weeks of abstinence before the onset of jaundice . Judgment regarding daily and long-term alcohol use and onset of jaundice will be made by the site investigator .
  4. The determination of AH may be based on typical serum chemistry (as determined by local laboratory) or liver biopsy at any time during the current episode of AH:
    • Serum total bilirubin > 3.0 mg/dL
    • 50 < AST < 400 IU/L
    • ALT < 400 IU/L
    • AST/ALT > 1.5
  5. Serum chemistry (as determined by local laboratory):
    • Serum total bilirubin > 3.0 mg/dL
    • 50 < AST < 400 IU/L
    • ALT < 400 IU/L
    • AST/ALT > 1.5
  6. Maddrey's Maddrey discriminant function (MDF) ≥ 32 assuming a control prothrombin time of 12 seconds.
  7. Model for End-stage Liver Disease (MELD) score: 21- 30 30.
  8. Liver biopsy is not required, but may be used to confirm the diagnosis of AH at the Investigator's discretion. Biopsy, if used as a diagnostic criterion, must have occurred during the current episode.
  9. Male or female subjects 18 years of age or older.
  10. When the diagnosis of AH remains in question, a liver biopsy (if clinically feasible and that subject has no contra-indications) will be required. Historical biopsy is allowed.
  11. Subjects must agree to use effective methods to prevent pregnancy while participating in the study.
  12. Subjects must agree to participate in an alcohol abstinence support program recommended by the local institution's addiction specialists.

Exclusion Criteria:

  1. Subjects taking systemic corticosteroids for a duration exceeding 7 8 days in the 30 days prior to screening.
  2. Subjects experiencing alcohol withdrawal symptoms or treatment with Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol Subjects experiencing or considered at high risk for alcohol withdrawal seizures or delirium tremens.
  3. Active infection (such as spontaneous bacterial peritonitis [SBP], urinary tract infection [UTI], bacteremia, acute viral hepatitis, uncontrolled HIV, and active SARS CoV2 infection).
  4. Active infection. Subjects who are febrile with leukocytosis are also excluded, even if there is no localizing diagnosis of infection.
  5. Serum creatinine >2.5 mg/ dL or eGFR < 60 mL/min/1.73 m2 dL.
  6. Subjects with acute kidney injury (AKl) or Hepatorenal syndrome
  7. Subjects undergoing continuous veno-venous hemodialysis (CVVH).
  8. Uncontrolled active gastrointestinal bleeding.
  9. A history of pre-admission refractory ascites defined as more than 4 paracenteses in the previous 8 weeks despite diuretic therapy.
  10. Refractory ascites
  11. Liver biopsy (if carried out) with findings not compatible with AH.
  12. Stage ≥3 hepatic encephalopathy by West Haven criteria.
  13. Any severe concomitant cardiovascular, renal, endocrine, pulmonary, psychiatric disorder, or multi-organ failure.
  14. Other concomitant cause(s) of liver disease.
  15. Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) or any other malignancy diagnosed within the last five years Any active malignancy or any malignancy diagnosed within the last five years other than curable skin cancer (basal cell or squamous cell carcinomas).
  16. Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications.
  17. Existing or intended pregnancy or breast feeding.
  18. Participation in another interventional clinical trial within 30 days of Screening.
  19. History of organ transplantation, other than a corneal transplant.
  20. Underlying diseases that, in the opinion of the site investigator, might be complicated or exacerbated by proposed treatments or might confound assessment of study drug.
Open or close this module Contacts/Locations
Central Contact Person: Christina Blevins, BS
Telephone: 408-777-1417
Email: christina.blevins@durect.com
Central Contact Backup: Deborah Scott, MS
Telephone: 408-777-1417
Email: deborah.scott@durect.com
Study Officials: Robert Gordon, MD, FACS
Study Director
CTI Clinical Trial and Consulting Services
Locations: United States, Alabama
Site 19
[Recruiting]
Birmingham, Alabama, United States, 35233
United States, Arizona
Site 18
[ Recruiting Withdrawn]
Phoenix, Arizona, United States, 85013
United States, California
Site 01
[Recruiting]
Coronado, California, United States, 92118
Site 42
[Recruiting]
Los Angeles, California, United States, 90033
Site 22
[Recruiting]
Los Angeles, California, United States, 90048
Site 43
[Recruiting]
Sacramento, California, United States, 95817
Site 38
[Recruiting]
San Francisco, California, United States, 94143
Site 24
[Recruiting]
Stanford, California, United States, 94305
United States, Connecticut
Site 30
[Recruiting]
New Haven, Connecticut, United States, 06510
United States, District of Columbia
Site 28
[Recruiting]
Washington, District of Columbia, United States, 20007
United States, Florida
Site 17
[ Recruiting Withdrawn]
Miami, Florida, United States, 33136
United States, Georgia
Site 02
[Recruiting]
Atlanta, Georgia, United States, 30309
United States, Illinois
Site 09
[Recruiting]
Chicago, Illinois, United States, 60611
Site 03
[Recruiting]
Chicago, Illinois, United States, 60612
Site 25
[Recruiting]
Chicago, Illinois, United States, 60637
Site 46
[Recruiting]
Maywood, Illinois, United States, 60153
United States, Indiana
Site 07
[Recruiting]
Indianapolis, Indiana, United States, 46202
United States, Kansas
Site 45
[Recruiting]
Kansas City, Kansas, United States, 66160
United States, Louisiana
Site 34
[Recruiting]
New Orleans, Louisiana, United States, 70112
United States, Maryland
Site 10
[Recruiting]
Baltimore, Maryland, United States, 21201
Site 26
[Recruiting]
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Site 44
[Recruiting]
Boston, Massachusetts, United States, 02111
Site 20
[Recruiting]
Boston, Massachusetts, United States, 02114
Site 27
[Withdrawn]
Burlington, Massachusetts, United States, 01805
United States, Michigan
Site 06
[Recruiting]
Detroit, Michigan, United States, 48202
United States, Minnesota
Site 37
[Recruiting]
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Site 40
[Recruiting]
Kansas City, Missouri, United States, 64111
Site 15
[Recruiting]
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Site 32
[Recruiting]
Omaha, Nebraska, United States, 68198
United States, New Jersey
Site 04
[Recruiting]
Newark, New Jersey, United States, 07103
United States, New Mexico
Site 39
[Recruiting]
Albuquerque, New Mexico, United States, 87106
United States, New York
Site 08
[Recruiting]
Manhasset, New York, United States, 11030
Site 23
[Recruiting]
New York, New York, United States, 10023
Site 21
[Recruiting]
New York, New York, United States, 10065
United States, North Carolina
Site 13
[Recruiting]
Charlotte, North Carolina, United States, 28204
United States, South Carolina
Site 33
[Recruiting]
Charleston, South Carolina, United States, 29425
United States, Texas
Site 11
[Recruiting]
Dallas, Texas, United States, 75203
Site 35
[Recruiting]
Dallas, Texas, United States, 75246
Site 31
[Recruiting]
Edinburg, Texas, United States, 78539
Site 12
[Recruiting]
Houston, Texas, United States, 77030
Site 29
[Recruiting]
Houston, Texas, United States, 77030
Site 36
[Recruiting]
Houston, Texas, United States, 77030
United States, Utah
Site 16
[Recruiting]
Salt Lake City, Utah, United States, 84132
United States, Virginia
Site 41
[Recruiting]
Charlottesville, Virginia, United States, 22908
Site 05
[Recruiting]
Richmond, Virginia, United States, 23226
United States, Washington
Site 14
[Recruiting]
Seattle, Washington, United States, 98104
Australia, New South Wales
Site 73
[Recruiting]
Camperdown, New South Wales, Australia, 2050
Site 74
[Recruiting]
Kingswood, New South Wales, Australia, 2217
Australia, Queensland
Site 75
[Recruiting]
South Brisbane, Queensland, Australia, 4101
Australia, South Australia
Site 71
[Recruiting]
Adelaide, South Australia, Australia, 5000
Site 70
[Recruiting]
Bedford Park, South Australia, Australia, 5042
Australia, Victoria
Site 72
[Recruiting]
Box Hill, Victoria, Australia, 3128
Australia, Western Australia
Site 77
[ Not yet recruiting Recruiting]
Nedlands, Western Australia, Australia, 6009
Site 76
[Recruiting]
Perth, Western Australia, Australia, 6000
Austria
Site 61
[Recruiting]
Graz, Austria, 8036
Belgium
Site 54
[Recruiting]
Brussels, Belgium, 1070
Site 55
[Recruiting]
Edegem, Belgium, 2650
France
Site 56
[Recruiting]
Besançon, France, 25000
Site 53
[ Not yet recruiting Recruiting]
Lille, France, 59037
Site 58
[Recruiting]
Lyon, France, 69004
Site 57
[Recruiting]
Marseille, France, 13008
United Kingdom, England
Site 50 60
[ Not yet recruiting Recruiting]
London, England, United Kingdom, SE5 9RS E1 1BB
Site 52 50
[ Not yet recruiting Recruiting]
London, England, United Kingdom, W2 1NY SE5 9RS
Site 52
[Recruiting]
London, England, United Kingdom, W2 1NY
Site 51
[Recruiting]
Plymouth, England, United Kingdom, PL6 8DH
United Kingdom, Scotland
Site 59
[Recruiting]
Dundee, Scotland, United Kingdom, DD1 9SY
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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