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Vidofludimus Calcium for Primary Sclerosing Cholangitis (PSC)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03722576
Recruitment Status : Completed
First Posted : October 29, 2018
Results First Posted : June 2, 2021
Last Update Posted : June 2, 2021
Sponsor:
Collaborator:
Arizona State University
Information provided by (Responsible Party):
Elizabeth Carey, Mayo Clinic

Brief Summary:
To examine the safety, tolerability, and efficacy of daily dosing with vidofludimus calcium over a 6-month period.

Condition or disease Intervention/treatment Phase
Primary Sclerosing Cholangitis Drug: Vidofludimus calcium Phase 2

Detailed Description:

Investigators will assess the following:

  1. Changes on serum alkaline phosphatase levels at 3 & 6 months.
  2. Changes in other liver biochemistries at 3 & 6 months.
  3. Changes in IL-17 &IFNγ levels at 6 weeks and 6 months.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Investigation of the Activity of Vidofludimus Calcium, a Novel, Orally Available, Small Molecule Inhibitor of Dihydroorotate Dehydrogenase, as a Treatment for Primary Sclerosing Cholangitis (PSC)
Actual Study Start Date : June 17, 2019
Actual Primary Completion Date : June 30, 2020
Actual Study Completion Date : June 30, 2020


Arm Intervention/treatment
Experimental: Vidofludimus Calcium (VC)
Daily dosing of VC over 6 months
Drug: Vidofludimus calcium
During the 6-month treatment period, subjects will receive 30 mg VC orally once daily. This will be preceded by a lead-in dosing period where subjects will receive 15 mg VC once daily for 1 week.
Other Name: IMU-838




Primary Outcome Measures :
  1. Subjects Who Experience a Positive Outcome as Measured by Combination of Serum Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST) Levels. [ Time Frame: 24 weeks ]
    The number of subjects who have both an ALP reduction from baseline to week 24 that is greater or equal to 25% and their AST increase from baseline is less than or equal to 33% at week 24. ALP measured as international units per liter (IU/L). AST measured as international units per liter (IU/L).


Secondary Outcome Measures :
  1. Abnormal Aspartate Aminotransferase (AST) [ Time Frame: 24 weeks ]
    Number of subjects with abnormal (not within normal range) AST levels. AST is an enzyme found in high amounts in liver, heart, and muscle cells. This test is mainly done along with other tests such as alkaline phosphatase and bilirubin to diagnose and monitor liver disease. This test evaluates hepatocyte integrity, as serum levels of this enzyme rise in response to a variety of forms of injury to hepatic cells. The normal range is 5 to 40 U/L . Units: U/L

  2. Abnormal Alanine Aminotransferase (ALT) [ Time Frame: 24 weeks ]
    Number of subjects with abnormal (not within normal range) ALT levels. An enzyme normally present in liver and heart cells that is released into the bloodstream when the liver or heart is damaged. The blood ALT levels are elevated with liver damage (for example, from viral hepatitis) or with an insult to the heart (for example, from a heart attack). The normal range is 7 to 56 U/L. Units: U/L

  3. Abnormal Total Bilirubin [ Time Frame: 24 weeks ]
    Number of subjects with abnormal (not within normal range) Total Bilirubin levels. Bilirubin is a yellowish pigment found in bile, a fluid made by the liver. A small amount of older red blood cells are replaced by new blood cells every day. Bilirubin is left after these older blood cells are removed. The liver helps break down bilirubin so that it can be removed from the body in the stool. The normal range for total bilirubin is 0.3 to 1.2 mg/dL Units: mg/dL

  4. Abnormal Direct Bilirubin [ Time Frame: 24 weeks ]
    Number of subjects with abnormal (not within normal range) direct bilirubin levels. In the liver, bilirubin is changed into a form that your body can get rid of. This is called conjugated bilirubin or direct bilirubin. This bilirubin travels from the liver into the small intestine. A very small amount passes into your kidneys and is excreted in your urine. Normal range for direct bilirubin is 0.3 and 1.2 milligrams per deciliter (mg/dL). Units: mg/dL



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subject age 18-75 years
  2. Diagnosis of PSC consistent with the guidelines published by the AASLD. All subjects must have an elevated serum ALP of at least 1.5 times upper limit of normal (ULN) at baseline plus cholangiographic evidence of PSC (MRI, endoscopic retrograde cholangiography, or direct cholangiography).
  3. Indirect bilirubin <1.2 times the ULN
  4. An ultrasound (or equivalent imaging modality) that excludes biliary obstruction and malignancy within 6 months of study enrollment
  5. PSC with or without inflammatory bowel disease, such as ulcerative colitis or Crohn's disease
  6. Must agree to comply with the study protocol and provide informed consent

Exclusion Criteria:

  1. Pregnancy, attempting to become pregnant, or breastfeeding
  2. Active hepatitis A or B infection
  3. Active 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
  4. HIV/AIDS (per medical record or HIVAb/HIA antigen), tuberculosis, or positive interferon-gamma assay (IGRAs) for Mycobacterium tuberculosis
  5. Other cholestatic liver disease such as primary biliary cholangitis and cholestatic diseases of pregnancy
  6. Metabolic liver diseases such as Wilson's disease, Gilbert's syndrome or hemochromatosis
  7. Serum uric acid levels at screening >1.2 ULN
  8. Inherited diseases of the liver such as α-1 antitrypsin deficiency
  9. Immunoglobulin G4-related cholangitis
  10. PSC with concomitant autoimmune hepatitis (AIH) and/or primary biliary cholangitis
  11. Secondary sclerosing cholangitis (SSC)
  12. Active acute ascending cholangitis requiring antibiotics
  13. CCA (malignant biliary stricture, neoplasm, and cytology/histopathology or positive fluorescence in situ hybridization (FISH) consistent with adenocarcinoma of the bile duct)
  14. 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.
  15. Presence of complications of advanced PSC such as hepatic encephalopathy, portal hypertension, hepato-renal syndrome, and hepato-pulmonary syndrome
  16. History of liver transplantation, anticipated need for liver transplantation within 12 months from randomization, a Model of End-stage Liver Disease (MELD) score of ≥15, or a Child Pugh score >6
  17. Ongoing alcohol abuse (>4 drinks per day for men, and >2 drinks per day for women)
  18. Moderate-to-severe renal impairment with a calculated creatinine clearance of <60mL/min
  19. 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
  20. Evidence of, or treatment for, C. difficile infection within 30 days before the initiation of the study drug
  21. Evidence of active C. difficile infection during the screening phase confirmed by a positive C. difficile toxin B
  22. Subjects who have been treated for intestinal pathogens other than C. difficile infection within 30 days prior to study drug initiation
  23. Received or plan to receive live vaccine within 30 days prior to, and through the end of the study
  24. Use of methotrexate at dose ≥17.5mg/week
  25. Rosuvastatin exceeding 10 mg daily

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): NCT03722576


Locations
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United States, Arizona
Mayo Clinic in Arizona
Phoenix, Arizona, United States, 85259
Arizona State University
Tempe, Arizona, United States, 85281
United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Elizabeth Carey
Arizona State University
Investigators
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Principal Investigator: Elizabeth Carey, MD Mayo Clinic
  Study Documents (Full-Text)

Documents provided by Elizabeth Carey, Mayo Clinic:
Additional Information:
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Responsible Party: Elizabeth Carey, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03722576    
Other Study ID Numbers: IND140679
First Posted: October 29, 2018    Key Record Dates
Results First Posted: June 2, 2021
Last Update Posted: June 2, 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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Cholangitis
Cholangitis, Sclerosing
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs