Vancomycin for Primary Sclerosing Cholangitis

A Prospective, Randomized, Multi-centered, Placebo-controlled Clinical Trial of Oral Vanycomycin in Adults With Primary Sclerosing Cholangitis

To find out if vancomycin is a safe and effective therapy for primary sclerosing cholangitis.

Funding Source - FDA OOPD

Study Overview

• Status: Recruiting
• Conditions: Primary Sclerosing Cholangitis
• Intervention / Treatment: Drug: Vancomycin; Other: Placebo

Detailed Description

A. Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6,12,and 18 months of OV treatment, and at 3, and 6 months post OV treatment will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.

B. Determine if OV stabilizes or improves liver fibrosis assessed by LSM using TE. Liver stiffness will be measured at 6, 12, and 18 months of OV treatment, and at 6 months post OV treatment, and values will be compared to those obtained at baseline (month 0), and with values in the placebo arm.

C. Determine the changes in the intestinal microbiota in relation to the use of OV, and study the correlation between the changes in the intestinal microbiota and the changes in: 1) liver enzymes, particularly serum ALP, and 2) liver stiffness, assessed by LSM using TE.

D. Determine if changes in proinflammatory cytokines (TGF-β, IL-4, IL-13, IL-10, etc.) predict response to OV. Cytokines will be measured at baseline, months 6, 12, 18, and at 3, and 6 months post OV treatment, if the study is positive.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Latasha Bunkley; Phone Number: 408-342-5756; Email: Bunkley.Latasha@mayo.edu

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic Arizona
      • Contact: Elizabeth Carey, MD; Phone Number: 480-342-1094
    • Tempe, Arizona, United States, 85281
      • Active, not recruiting
      • Arizona State University
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
      • Contact: Denise M Harnois, DO; Phone Number: 904-956-3258
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
      • Contact: John Eaton, MD; Phone Number: 507-284-3917

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subject age 18-76 years
2. Diagnosis of PSC consistent with the guidelines published by the American Association for the Study of Liver Diseases (AASLD).39 All subjects must have an elevated serum ALP of at least 1.5 times upper limit of normal at baseline plus cholangiographic evidence of PSC, as demonstrated by magnetic resonance imaging, endoscopic retrograde cholangiography, direct cholangiography, or liver biopsy.
3. Total bilirubin at screening must be ≤ 2 times upper limit of normal
4. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and malignancy within 6 months of study entry,
5. If a patient is on any of the following medications and/or supplements, he or she is expected to remain on the same daily dose through the treatment period: UDCA, azathioprine, prednisone (or an equivalent steroid compound), methotrexate, a 5-aminosalicylic acid, biologic therapy, and/or a probiotic.
6. If a patient has been on obeticholic acid or other experimental therapies for PSC, they must complete a 3 month washout period before study entry
7. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's disease
8. Must agree to comply with the study protocol and provide informed consent.

Exclusion Criteria:

1. Administration of an antibiotic within 3 months prior to the study,
2. Pregnancy or attempting to become pregnant or breastfeeding,

3. Presence of any of the following:

   i. Hepatitis B infection

   ii. Hepatitis C infection (antibody positive); patients with a history of hepatitis C infection will be eligible for this study if they have undetectable levels of HCV RNA

   iii. Other cholestatic liver diseases such as primary biliary cholangitis and cholestatic diseases of pregnancy

   iv. Metabolic liver diseases such as Wilson's disease and hemochromatosis

   v. Inherited diseases of the liver such as α-1 antitrypsin deficiency

   vi. Immunoglobulin G4-related cholangitis

   vii. PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis (previously known as primary biliary cirrhosis)

   viii. Secondary sclerosing cholangitis (SSC),

   ix. Active acute ascending cholangitis requiring antibiotics

   x. CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile duct)

   xi. A liver biopsy, if one has been previously obtained, which showed non-alcoholic steatohepatitis (NASH). Patients with suspected fatty liver by imaging will not be excluded

   xii. Presence of decompensated cirrhosis such as hepatic encephalopathy, hepato-renal syndrome and hepato-pulmonary syndrome,

   xiii. History of liver transplantation, anticipated need for liver transplantation within 12 months from randomization, or a Model of End Stage Liver Disease (MELD) score of ≥15

   xiv. Ongoing alcohol abuse (>4 drinks per day for men, and >2 drinks per day for women)

   xv. History of allergic reaction to vancomycin,

   xvi. Moderate-to-severe renal impairment with a calculated creatinine clearance of < 60mL/min

   xvii. HIV/AIDS,

   xviii. Any other conditions or abnormalities that, in the opinion of the investigator, may compromise the safety of the subject or interfere with the subject participating in or completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo for Vancomycin
Experimental: Vancomycin	Drug: Vancomycin; Firvanq by Azurity Pharmaceuticals, Inc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alkaline phosphatase at 6 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	6 months
Alkaline phosphatase at 12 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 12 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	12 months
Alkaline phosphatase at 18 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 18 months of OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	18 months
Alkaline phosphatase at 3 months post treatment = 21 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 3 months post OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	21 months
Alkaline phosphatase at 6 months post treatment = 24 months	Determine if OV normalizes serum ALP in adults with PSC. Levels of serum ALP obtained at 6 months post OV treatment, and will be compared to those obtained at baseline (month 0), and with values at the same study time points in the placebo arm.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibroscan, cholangiography	Transient elastography (TE), a new technique that allows non-invasive assessment and follow up of liver fibrosis by measuring liver stiffness, differentiates between severe from non-severe fibrosis in PSC, and the rate of progression of liver stiffness measurement (LSM) assessed by TE correlates well with the rate of progression of fibrosis in PSC and with patients' clinical outcomes.	18 months

Collaborators and Investigators

• Sponsor: Elizabeth Carey
• Collaborators: Arizona State University
• Investigators: Principal Investigator: Elizabeth Carey, MD, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: October 15, 2018
• First Submitted That Met QC Criteria: October 15, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholangitis; Cholangitis, Sclerosing; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin
• Other Study ID Numbers: 18-003439; FD-R-6102 (Other Grant/Funding Number: FDA OOPD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No