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AHFIRM: A Phase 2b Study in Subjects With Alcoholic Hepatitis to Evaluate Safety and Efficacy of DUR-928 Treatment

Sponsor
Durect (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04563026
Collaborator
CTI Clinical Trial and Consulting Services (Other)
300
Enrollment
66
Locations
3
Arms
31.3
Anticipated Duration (Months)
4.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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).

Condition or Disease Intervention/Treatment Phase
  • Drug: DUR-928 30 mg
  • Drug: DUR-928 90 mg
  • Drug: Placebo+ Standard of Care (SOC)
 Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.This is a Phase 2b randomized, double-blind, placebo-controlled, multi-arm, multi-center, parallel design trial.
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, Phase 2b Study to Evaluate Safety and Efficacy of DUR-928 in Subjects With Alcoholic Hepatitis
Actual Study Start Date :
Jan 22, 2021
Anticipated Primary Completion Date :
Sep 1, 2023
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

Arm Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

  1. Difference in 90-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo. [Day 90]

Secondary Outcome Measures

  1. Difference in 90-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo. [Day 90]

  2. Difference in 28-day mortality or liver transplant between IV DUR-928, 30 mg or 90 mg, and placebo. [Day 28]

  3. Difference in 28-day mortality between IV DUR-928, 30 mg or 90 mg, and placebo. [Day 28]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.

  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

  1. Maddrey discriminant function (MDF) ≥ 32 assuming a control prothrombin time of 12 seconds.

  2. Model for End-stage Liver Disease (MELD) score: 21-30.

  3. 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.

  4. Male or female subjects 18 years of age or older.

  5. Subjects must agree to use effective methods to prevent pregnancy while participating in the study.

  6. 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 8 days in the 30 days prior to screening.

  2. 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. Serum creatinine >2.5 mg/dL.

  5. Subjects undergoing continuous veno-venous hemodialysis (CVVH).

  6. Uncontrolled gastrointestinal bleeding.

  7. A history of pre-admission refractory ascites defined as more than 4 paracenteses in the previous 8 weeks despite diuretic therapy.

  8. Liver biopsy (if carried out) with findings not compatible with AH.

  9. Stage ≥3 hepatic encephalopathy by West Haven criteria.

  10. Any severe concomitant cardiovascular, renal, endocrine, pulmonary, psychiatric disorder, or multi-organ failure.

  11. Other concomitant cause(s) of liver disease.

  12. Any active malignancy or any malignancy diagnosed within the last five years other than curable skin cancer (basal cell or squamous cell carcinomas).

  13. Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and prescription medications.

  14. Existing or intended pregnancy or breast feeding.

  15. Participation in another interventional clinical trial within 30 days of Screening.

  16. History of organ transplantation, other than a corneal transplant.

  17. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Site 19 Birmingham Alabama United States 35233
2 Site 18 Phoenix Arizona United States 85013
3 Site 01 Coronado California United States 92118
4 Site 42 Los Angeles California United States 90033
5 Site 22 Los Angeles California United States 90048
6 Site 43 Sacramento California United States 95817
7 Site 38 San Francisco California United States 94143
8 Site 24 Stanford California United States 94305
9 Site 30 New Haven Connecticut United States 06510
10 Site 28 Washington District of Columbia United States 20007
11 Site 17 Miami Florida United States 33136
12 Site 02 Atlanta Georgia United States 30309
13 Site 09 Chicago Illinois United States 60611
14 Site 03 Chicago Illinois United States 60612
15 Site 25 Chicago Illinois United States 60637
16 Site 46 Maywood Illinois United States 60153
17 Site 07 Indianapolis Indiana United States 46202
18 Site 45 Kansas City Kansas United States 66160
19 Site 34 New Orleans Louisiana United States 70112
20 Site 10 Baltimore Maryland United States 21201
21 Site 26 Baltimore Maryland United States 21205
22 Site 44 Boston Massachusetts United States 02111
23 Site 20 Boston Massachusetts United States 02114
24 Site 27 Burlington Massachusetts United States 01805
25 Site 06 Detroit Michigan United States 48202
26 Site 37 Minneapolis Minnesota United States 55455
27 Site 40 Kansas City Missouri United States 64111
28 Site 15 Saint Louis Missouri United States 63110
29 Site 32 Omaha Nebraska United States 68198
30 Site 04 Newark New Jersey United States 07103
31 Site 39 Albuquerque New Mexico United States 87106
32 Site 08 Manhasset New York United States 11030
33 Site 23 New York New York United States 10023
34 Site 21 New York New York United States 10065
35 Site 13 Charlotte North Carolina United States 28204
36 Site 33 Charleston South Carolina United States 29425
37 Site 11 Dallas Texas United States 75203
38 Site 35 Dallas Texas United States 75246
39 Site 31 Edinburg Texas United States 78539
40 Site 12 Houston Texas United States 77030
41 Site 29 Houston Texas United States 77030
42 Site 36 Houston Texas United States 77030
43 Site 16 Salt Lake City Utah United States 84132
44 Site 41 Charlottesville Virginia United States 22908
45 Site 05 Richmond Virginia United States 23226
46 Site 14 Seattle Washington United States 98104
47 Site 73 Camperdown New South Wales Australia 2050
48 Site 74 Kingswood New South Wales Australia 2217
49 Site 75 South Brisbane Queensland Australia 4101
50 Site 71 Adelaide South Australia Australia 5000
51 Site 70 Bedford Park South Australia Australia 5042
52 Site 72 Box Hill Victoria Australia 3128
53 Site 77 Nedlands Western Australia Australia 6009
54 Site 76 Perth Western Australia Australia 6000
55 Site 61 Graz Austria 8036
56 Site 54 Brussels Belgium 1070
57 Site 55 Edegem Belgium 2650
58 Site 56 Besançon France 25000
59 Site 53 Lille France 59037
60 Site 58 Lyon France 69004
61 Site 57 Marseille France 13008
62 Site 60 London England United Kingdom E1 1BB
63 Site 50 London England United Kingdom SE5 9RS
64 Site 52 London England United Kingdom W2 1NY
65 Site 51 Plymouth England United Kingdom PL6 8DH
66 Site 59 Dundee Scotland United Kingdom DD1 9SY

Sponsors and Collaborators

  • Durect
  • CTI Clinical Trial and Consulting Services

Investigators

  • Study Director: Robert Gordon, MD, FACS, CTI Clinical Trial and Consulting Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Durect
ClinicalTrials.gov Identifier:
NCT04563026
Other Study ID Numbers:
  • C928-011
First Posted:
Sep 24, 2020
Last Update Posted:
Aug 10, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Durect
Alcoholic Hepatitis
acute alcoholic liver disease
progressive inflammatory liver injury
Additional relevant MeSH terms:
Hepatitis A
Hepatitis
Hepatitis, Alcoholic

Study Results

No Results Posted as of Aug 10, 2022