Summary

Eligibility
for people ages 21 years and up (full criteria)
Location
at La Jolla, California
Dates
study started
estimated completion
Principal Investigator
by Rohit Loomba
Photo of Rohit Loomba
Rohit Loomba

Description

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.

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

Keywords

Alcoholic Liver Disease Liver Diseases Liver Diseases, Alcoholic Antibodies, Monoclonal Guselkumab 30mg Guselkumab 70mg Guselkumab 100mg Guselkumab 70 mg

Eligibility

You can join if…

Open to people ages 21 years and up

  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:
  11. Markedly increased amounts of the alcohol in order to achieve intoxication or desired effect
  12. Markedly diminished effect with continued use of the same amount
  13. Withdrawal, as manifested by either of the following:
  14. The characteristic alcohol withdrawal syndrome or
  15. Alcohol (or a closely related substance) is taken to relieve or avoid withdrawal symptoms
  16. Evidence of end-organ damage to the liver as defined by
  17. MRI-PDFF ≥ 8% suggestive of significant hepatic accumulation of triglyceride within 3 months of screening; if patients cannot get an MRI, CAP ≥ 300dB/m
  18. Consumed alcohol within 12 weeks of entry into the study, AND
  19. AST and ALT less than 200 U/L AND
  20. No evidence of active infection as determined by the investigator.
  21. 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.
  22. Male patients must agree to use a medically acceptable method of contraception/birth control throughout the study duration.

You CAN'T join if...

  1. History or evidence of other or concomitant cause(s) of liver disease as a result of:
  2. Autoimmune liver disease
  3. Wilson disease (ceruloplasmin levels < 10 mcg/L)
  4. Vascular liver disease
  5. Drug induced liver disease
  6. Surface antigen positive hepatitis B (HBsAg+). Note: patients with isolated core antibody (HBcAb) are not excluded.
  7. Acute hepatitis A
  8. 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)
  9. Noninvasive criteria to exclude cirrhosis:
  10. MRE ≥ 3.63 kPa; if MRE not available, VCTE ≥ 16 kPa
  11. FIB-4 ≥ 2.67
  12. Imaging evidence of varices, splenomegaly, ascites, or shrunken cirrhotic liver
  13. Co-infection with human immunodeficiency virus (HIV)
  14. History or evidence of positive Urine Drug Screen (amphetamines, barbiturates, benzodiazepines, cocaine and opiates) except THC and legal prescription medications.
  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
  16. History or evidence of active tuberculosis
  17. Positive Quantiferon test
  18. 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
  19. Patients requiring the use of vasopressors or inotropic support.
  20. . 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
  21. . Patients who are taking drug products that are primarily the substrates of CYP2C8, such as chloroquine, paclitaxel, rosiglitazone, repaglinide
  22. . If female, known pregnancy, or has a positive serum pregnancy test, or is lactating/breastfeeding
  23. . Serum creatinine > 1.5 mg/dL
  24. . Patients who have had organ transplantation (such as liver, kidney, lung, heart, bone marrow, or stem cell etc.), other than cornea transplant
  25. . Presence of cirrhosis on imaging or any of following lab parameters:
  26. Albumin < 3.7 g/dL
  27. Direct bilirubin > 0.5 mg/dl unless due to Gilbert's syndrome
  28. Platelets < 140K
  29. INR > 1.3
  30. . Presence of any features of portal hypertension such as ascites, history of ascites or varices, or encephalopathy
  31. . Previous use of guselkumab ( or another IL-23 inhibitors) or hypersentivity to guselkumab
  32. . Previous history of skin cancers in the last one year
  33. . Previous history of breast or prostate cancer or any cancer within the last 5 years

Location

  • University of California, San Diego accepting new patients
    La Jolla California 92093 United States

Lead Scientist at UCSD

  • Rohit Loomba
    NAFLD Research Center Center for Microbiome Innovation Collapse Websites [IMAGE] Loomba Lab [IMAGE] Patient Website [IMAGE] Liver Epidemiology Fellowship [IMAGE] Division of Gastroenterology [IMAGE] Department of Family Medicine and Public Health [IMAGE] Division of Epidemiology [IMAGE] Clinical Profile

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Diego
ID
NCT04736966
Phase
Phase 1
Study Type
Interventional
Last Updated