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Guselkumab (Anti-IL 23 Monoclonal Antibody) for Alcohol Associated Liver Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04736966
Recruitment Status : Recruiting
First Posted : February 3, 2021
Last Update Posted : May 5, 2021
Sponsor:
Information provided by (Responsible Party):
Rohit Loomba, University of California, San Diego

Brief Summary:
This is a phase I study of guselkumab, a humanized anti-IL23 monoclonal antibody, for patients with alcoholic liver disease. This drug is approved for the use in psoriatic arthritis but not for alcoholic liver disease. The investigators will be using a standard 3+3 phase I dose escalation trial design, the dose levels will start from 30 mg, 70 mg and to 100 mg, a maximum total of 24 patients will be evaluable. In this study the investigators propose to establish safety of the product in those with alcoholic liver disease and efficacy (secondary endpoint) will be determined by biomarkers for liver inflammation and fibrosis surrogate biomarkers.

Condition or disease Intervention/treatment Phase
Alcoholic Liver Disease Drug: Guselkumab 30mg Drug: Guselkumab 70mg Drug: Guselkumab 100mg Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Determine the Safety and Tolerability of Anti-IL23 Monoclonal Antibody, for the Treatment of Patients With Alcohol Associated Liver Disease
Actual Study Start Date : March 3, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : March 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases
Drug Information available for: Guselkumab

Arm Intervention/treatment
Experimental: Guselkumab 30mg Drug: Guselkumab 30mg
30mg of Guselkumab administered by subcutaneous injection

Experimental: Guselkumab 70 mg Drug: Guselkumab 70mg
70mg of Guselkumab administered by subcutaneous injection

Experimental: Guselkumab 100mg Drug: Guselkumab 100mg
100mg of Guselkumab administered by subcutaneous injection




Primary Outcome Measures :
  1. Assess the safety and tolerability of Guselkumab [ Time Frame: 48 Weeks ]
    Incidence of treatment-emergent adverse events: Outcome measures will include incidence of treatment-emergent adverse events and the proportion of subjects prematurely withdrawn from the study due to adverse events.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 ≤ 45 kg/m2
  3. Patients with moderate alcohol use disorder (AUD) as defined by the AASLD Practice Guidance to have ≥ 4 symptoms out of 11:

    1. Alcohol is often taken in larger amounts and/or over a longer period than the patient intended.
    2. Persistent attempts or one or more unsuccessful efforts made to cut down or control alcohol use.
    3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from effects.
    4. Craving or strong desire or urge to use alcohol
    5. Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school, or home.
    6. Continued alcohol use despite having persistent or recurrent social or interpersonal problem caused or exacerbated by the effects of the alcohol.
    7. Important social, occupational or recreational activities given up or reduced because of alcohol use.
    8. Recurrent alcohol use in situations in which it is physically hazardous.
    9. Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the alcohol.
    10. Tolerance, as defined by either of the following:
    1. Markedly increased amounts of the alcohol in order to achieve intoxication or desired effect
    2. Markedly diminished effect with continued use of the same amount

    k. Withdrawal, as manifested by either of the following:

    1. The characteristic alcohol withdrawal syndrome or
    2. Alcohol (or a closely related substance) is taken to relieve or avoid withdrawal symptoms
  4. Evidence of end-organ damage to the liver as defined by

    a. MRI-PDFF ≥ 8% suggestive of significant hepatic accumulation of triglyceride within 3 months of screening; if patients cannot get an MRI, CAP ≥ 300dB/m

  5. Consumed alcohol within 12 weeks of entry into the study, AND

    a. AST and ALT less than 200 U/L AND

  6. No evidence of active infection as determined by the investigator.
  7. 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.
  8. Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration.

Exclusion Criteria:

  1. History or evidence of other or concomitant cause(s) of liver disease as a result of:

    1. Autoimmune liver disease
    2. Wilson disease (ceruloplasmin levels < 10 mcg/L)
    3. Vascular liver disease
    4. Drug induced liver disease
    5. Surface antigen positive hepatitis B (HBsAg+). Note: patients with isolated core antibody (HBcAb) are not excluded.
    6. Acute hepatitis A
    7. 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. Anti-HBc antibody positive patients will be given a prophylaxis with entecavir 0.5mg PO once daily, starting one week prior to start of guselkumab to 6 months after the last dose of guselkumab)
  2. Noninvasive criteria to exclude cirrhosis:

    1. MRE ≥ 3.63 kPa; if MRE not available, VCTE ≥ 16 kPa
    2. FIB-4 ≥ 2.67
    3. Imaging evidence of varices, splenomegaly, ascites, or shrunken cirrhotic liver
  3. Co-infection with human immunodeficiency virus (HIV)
  4. History or evidence of positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and legal prescription medications.
  5. 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
  6. History or evidence of active tuberculosis
  7. Positive Quantiferon test
  8. 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
  9. Patients requiring the use of vasopressors or inotropic support.
  10. Any patient that has received any investigational drug within 30 days of dosing or who is scheduled to receive another investigational drug at any time during the study
  11. Patients who are taking drug products that are primarily the substrates of CYP2C8, such as chloroquine, paclitaxel, rosiglitazone, repaglinide
  12. If female, known pregnancy, or has a positive serum pregnancy test, or is lactating/breastfeeding
  13. Serum creatinine > 1.5 mg/dL
  14. Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant
  15. Presence of cirrhosis on imaging or any of following lab parameters:

    1. Albumin < 3.7 g/dL
    2. Direct bilirubin > 0.5 mg/dl unless due to Gilbert's syndrome
    3. Platelets < 140K
    4. INR > 1.3
  16. Presence of any features of portal hypertension such as ascites, history of ascites or varices, or encephalopathy
  17. Previous use of guselkumab ( or another IL-23 inhibitors) or hypersentivity to guselkumab
  18. Previous history of skin cancers in the last one year
  19. Previous history of breast or prostate cancer or any cancer within the last 5 years

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04736966


Contacts
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Contact: Lori Edge 858-246-5333 ledge@health.ucsd.edu

Locations
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United States, California
University of California, San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Lori Edge    858-246-5333    ledge@health.ucsd.edu   
Sponsors and Collaborators
University of California, San Diego
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Responsible Party: Rohit Loomba, Professor of Medicine, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04736966    
Other Study ID Numbers: Anti-IL23 Trial Phase 1
First Posted: February 3, 2021    Key Record Dates
Last Update Posted: May 5, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Liver Diseases, Alcoholic
Digestive System Diseases
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs