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Alcoholic HepatitisPhase 2DUR-928/AHNCT03917407

DUR-928 in Patients With Alcoholic Hepatitis

A Phase 2 study testing DUR-928 (Moderate AH) and DUR-928 (Severe AH) in people with Alcoholic Hepatitis, run by Craig James McClain at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The proposed study is An Open-Label, Dose Escalation Study to Assess the Safety, and Pharmacodynamics (PD) signals of DUR 928 in Patients with AH. DUR-928 will be administered in 100 mL 5% dextrose or 0.9% sodium chloride by slow intravenous infusion over 2 hrs (50mL/h) until entire dose is given at Day 1 and Day 4. Read more about this study

Who is it for?
Ages 21 to 67 years
Conditions the study is for
Alcoholic Hepatitis
What is being tested?
DUR-928 (Moderate AH) and DUR-928 (Severe AH)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
1 Jun 2021to 30 Sep 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 67 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • MELD score between 11-30, inclusive
  • No evidence of active infection as determined by the investigator. If infection is initially suspected clinically,
  • blood cultures, urine cultures, and peritoneal cultures should be without growth for 48 hrs, AND
  • peritoneal cell count should be less than 250 Polymorphonuclear cell (PMN)/ml. If infection is diagnosed, then the infection must be
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  • treated with antibiotics, AND
  • documented negative blood cultures for 48 hrs, or for spontaneous bacterial peritonitis (SBP) 25% reduction in PMN count prior to enrollment.
  • Women of child-bearing potential (defined as females who are not surgically sterile or who are not over the age of 52 and amenorrheic for at least 12 months) must utilize appropriate birth control throughout the study duration. Acceptable methods that may be used are abstinence, birth control pills ("The Pill") or patch, diaphragm, intrauterine device (IUD/ coil), vaginal ring, condom, surgical sterilization or progestin implant or injection, or sexual activity limited to a sterile (e.g., vasectomized) male partner.
  • Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration.

Who cannot join

  • Other or concomitant cause(s) of liver disease as a result of:
  • Autoimmune liver disease (positive anti-mitochondrial antibody and smooth muscle antibody, positive reading on anti-nuclear antibody titer > 1:160)
  • Wilson disease (ceruloplasmin levels < 10 mcg/L)
  • Vascular liver disease
  • Drug induced liver disease
  • Surface antigen positive hepatitis B (HBsAg+). Note: patients with isolated core antibody (HBcAb) are not excluded.
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  • Acute hepatitis A
  • Acute HCV or chronic hepatitis C with a history of decompensated cirrhosis. Note: patients with stable chronic Hep C Virus (HCV) or successfully treated HCV are not excluded.
  • Co-infection with human immunodeficiency virus (HIV)
  • Positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and legal prescription medications.
  • 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
  • Active tuberculosis on chest x-ray at study entry
  • Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious psychiatric disease, that, in the opinion of the Investigator would preclude the patient from participating in and completing the study
  • Patients requiring the use of vasopressors or inotropic support. Prior use of inotropic support will be allowed if the condition has stabilized within the first 7 days of admission to the hospital
  • Liver biopsy, if carried out, showing findings not compatible with AH
  • Any patient that has received any investigational drug or device within 30 days of dosing or who is scheduled to receive another investigational drug or device at any time during the study
  • Patients who are taking drug products that are primarily the substrates of CYP2C8, such as chloroquine, paclitaxel, rosiglitazone, repaglinide
  • If female, known pregnancy, or has a positive serum pregnancy test, or is 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Louisville

    Louisville, Kentucky, 40202

Other trials in United States

About this study

Official title: U01 Pilot Trial of DUR-928 in Patients With Moderate and Severe Alcoholic Hepatitis

The proposed study is An Open-Label, Dose Escalation Study to Assess the Safety, and Pharmacodynamics (PD) signals of DUR 928 in Patients with AH. DUR-928 will be administered in 100 mL 5% dextrose or 0.9% sodium chloride by slow intravenous infusion over 2 hrs (50mL/h) until entire dose is given at Day 1 and Day 4. If a patient meets the hospital discharge criteria prior to the 2nd dose, the patient will receive only one dose of DUR-928 instead of 2 doses.

Read the detailed description

The study will be conducted in 2 Parts using a staggered parallel design. Part A will include patients with MELD scores of 11-20, and Part B will include patients with MELD of scores 21-30.

Within each Part, the study will be conducted using a starting dose level of 30 mg with sequential dose escalation following review of safety results of the prior dose level by the sponsor, the principal investigators. The planned subsequent doses of DUR-928 after the starting dose are 90 mg and 150 mg.

Patients with a MELD score of 21-30 (Part B) receiving the 30 mg dose level will only be enrolled once safety review of the 30 mg dose of DUR-928 in patients with MELD score 11-20 (Part A) has been completed. The subsequent dose escalation in Part B will not proceed until the sponsor, and the principal investigators, and the medical monitor complete the review of safety of the 30 mg dose level and determine it is safe to do so.

At each dose level within a Part, 4 patients will be treated. If no SUSAR is observed, dose escalation to the next dose cohort within the Part will proceed. If 1 of the 4 patients demonstrates a SUSAR in a given dose level, an additional 2 patients will be treated at that dose level. If only 1 of the 6 patients demonstrates SUSAR, the next cohort of four patients will enter at the next dose level. If 6 patients are dosed and 2 or more demonstrate SUSAR at that dose level, the study will deescalate to a lower dose (but higher than the previous dose). At subsequent dose levels, the maximum tolerated dose (MTD) is defined as the dose level where no more than 1 of 6 patients experiences a SUSAR.

If no SUSAR is observed, dose escalation to the next dose cohort will proceed. All patients will be followed up to Day 28 (Total duration of patient engagement is 33 days).

Trial Population:

Patients with AH will be enrolled at Louisville associated hospitals in the US. The target number of participants to complete the study is 24-36. During the trial, patients should receive standard of care as determined by the PI (e.g. pentoxifylline or corticosteroids).

Being tested
DUR-928 (Moderate AH), DUR-928 (Severe AH)
Keywords
Alcoholic Hepatitis, Alcoholic Liver Disease
Medical subject headings
Hepatitis, Alcoholic, Liver Diseases, Alcoholic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DUR-928 (Moderate AH)Drug

    Also called Sulfated oxysterol: 5 cholesten-3β, 25-diol 3-sulfate (25HC3S)

    A total of no more than two doses of DUR-928 will be given, with 72 hrs between each dose. A second dose of the assigned study treatment (test drug) will be repeated 3 days after Dose 1 to patients who are still hospitalized. If a patient meets the discharge criteria prior to Day 4, the patient will receive only one dose of DUR 928.

    Patients of Part A (MELD 11-20) will follow the dose escalation procedure based on cohort; each patient will receive an intravenous infusion dose of:

    • Cohort 1A: 30 mg of DUR-928in 100 mL 5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.
    • Cohort 2A: 90 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.
    • Cohort 3A: 150 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.

  • DUR-928 (Severe AH)Drug

    Also called Sulfated oxysterol: 5 cholesten-3β, 25-diol 3-sulfate (25HC3S)

    Dose escalation to the next cohort will be determined after review of safety, tolerability and pharmacokinetic data of the previous cohort. Dose escalation for Part B will follow the same requirements as for Part A. The dose levels for Part B are planned to be the same as Part A.

    Patients of Part B (MELD 21-30) will follow the dose escalation procedure based on cohort; each patient will receive an intravenous infusion dose of:

    • Cohort 1B: 30 mg of DUR-928 in 100 mL 5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.
    • Cohort 2B: 90 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion.
    • Cohort 3B: 150 mg of DUR 928 in 100 mL5% dextrose or 0.9% sodium chloride administered over approximately 2 hrs via IV infusion More details on preparation and administration of study drug will be provided in the Investigation Product Manual for this study.
Study groups in NCT03917407
Study groupRoleWhat they receive
Arm1: DUR-928 treatment for moderate alcoholic hepatitisActive comparatorEnrolled alcoholic hepatitis patients would have MELD of 11-20; and have met inclusion and exclusion criteria. DUR-928 as a novel study treatment would be administered in patients with moderate alcoholic hepatitis (AH) as determined by the absence of suspected unexpected serious adverse reaction (SUSAR).
Receives: Drug: DUR-928 (Moderate AH)
Arm 2: DUR-928 treatment for severe alcoholic hepatitis.Active comparatorEnrolled alcoholic hepatitis patients would have MELD of 21-30; and have met inclusion and exclusion criteria. DUR-928 as a novel study treatment would be administered in patients with severe alcoholic hepatitis (AH) as determined by the absence of suspected unexpected serious adverse reaction (SUSAR).
Receives: Drug: DUR-928 (Severe AH)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of Treatment-Emergent Adverse Events

    Assess the safety and tolerability of DUR-928 in patients with alcoholic hepatitis (AH) as determined by the absence of suspected unexpected serious adverse reaction (SUSAR).

    Measured: 4.5 years.

  2. Pharmacodynamic signals of DUR-928: Model for End-Stage Liver Disease [MELD]

    Drivers of the Model for End-Stage Liver Disease [MELD] score individually using a formula (3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43 that incorporates following lab measures: International Normalized Ratio [INR], and Serum Creatinine and Serum Total Bilirubin [units for both: mg/dl]) at baseline, Day 7 and Day 28. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  3. Pharmacodynamic signals of DUR-928: Liver Biochemical Biomarker "Alanine Aminotransferase"

    Improvement in liver biochemistry at baseline, Day 7 and Day 28 (Alanine Aminotransferase [ALT, unit: IU/L]. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  4. Pharmacodynamic signals of DUR-928: Liver Biochemical Biomarker "Aspartate Aminotransferase"

    Improvement in liver biochemistry at baseline, Day 7 and Day 28 for Aspartate Aminotransferase [AST, unit: IU/L]. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  5. Pharmacodynamic signals of DUR-928: Liver Biochemical Biomarker "Total Bilirubin"

    Improvement in liver biochemistry at baseline, Day 7 and Day 28 for Total Bilirubin [unit: mg/dl]. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  6. Pharmacodynamic signals of DUR-928: Liver Biochemical Biomarker "Albumin"

    Improvement in liver biochemistry at baseline, Day 7 and Day 28 for Albumin [unit: g/L]. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  7. Quality of life biomarkers: 36-item Short Form Survey (SF-36).

    Quality of Life biomarkers (eg. SF-36) at Baseline, Day 7 and Day 28. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  8. Biomarkers of liver cell death: Cytokeratin 18 (CK18)

    Novel liver cell death markers: Cytokeratin18M65 (K18M65), and Cytokeratin18M30 (K18M30). Units: IU/L. Evaluation at baseline, day 7 and day 28. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  9. Biomarkers of Inflammation (Interleukins): Interleukin 6 and Interleukin 8

    interleukin 6 (IL6, unit: pg/mL) and Interleukin 8 (IL8, unit: pg/mL) at baseline, day 7 and day 28. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

  10. Biomarkers of Inflammation: C-reactive Protein

    C-reactive Protein (CRP, unit: mg/dL) assessed at baseline, day 7 and days 28. Participant's involvement in study: 33 days maximum.

    Measured: 33 days.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2019
  2. Study start1 Jun 2021
  3. Primary completion24 Sep 2023
  4. Study completion30 Sep 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
An Open-Label, Dose Escalation Study to Assess the Safety, and Pharmacodynamics signals of DUR 928 in Patients with AH. DUR-928 will be administered in 100 mL 5% dextrose or 0.9% sodium chloride by slow intravenous infusion over 2 hrs (50mL/h) until entire dose is given at Day 1 and Day 4. If a patient meets the hospital discharge criteria prior to the 2nddose, the patient will receive only one dose of DUR-928 instead of 2 doses.
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03917407
Sponsor's protocol ID
19.0776
Other IDs
1U01AA026934-01
Acronym
DUR-928/AH
Status last verified
Oct 2023
First submitted
27 Mar 2019
Last updated
18 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: There is not a plan to make Individual patient data (IPD) available.

Publications

  • Liangpunsakul S. Clinical characteristics and mortality of hospitalized alcoholic hepatitis patients in the United States. J Clin Gastroenterol. 2011 Sep;45(8):714-9. doi: 10.1097/MCG.0b013e3181fdef1d.

    PubMed 21085006

  • Menon KV, Gores GJ, Shah VH. Pathogenesis, diagnosis, and treatment of alcoholic liver disease. Mayo Clin Proc. 2001 Oct;76(10):1021-9. doi: 10.4065/76.10.1021.

    PubMed 11605686

  • FDA, Draft guidance for Drug Interaction Studies. February 2012.

  • Orman ES, Odena G, Bataller R. Alcoholic liver disease: pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol. 2013 Aug;28 Suppl 1(0 1):77-84. doi: 10.1111/jgh.12030.

    PubMed 23855300

  • O'Shea RS, McCullough AJ. Treatment of alcoholic hepatitis. Clin Liver Dis. 2005 Feb;9(1):103-34. doi: 10.1016/j.cld.2004.11.004.

    PubMed 15763232

  • Thursz MR, Richardson P, Allison M, Austin A, Bowers M, Day CP, Downs N, Gleeson D, MacGilchrist A, Grant A, Hood S, Masson S, McCune A, Mellor J, O'Grady J, Patch D, Ratcliffe I, Roderick P, Stanton L, Vergis N, Wright M, Ryder S, Forrest EH; STOPAH Trial. Prednisolone or pentoxifylline for alcoholic hepatitis. N Engl J Med. 2015 Apr 23;372(17):1619-28. doi: 10.1056/NEJMoa1412278.

    PubMed 25901427

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DUR-928 (Moderate AH) and DUR-928 (Severe AH) in people with Alcoholic Hepatitis, run by Craig James McClain at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of Treatment-Emergent Adverse Events (time frame: 4.5 years.). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03917407, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Oct 2023.

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