Oral Hymecromone to Treat Adolescents and Adults With Primary Sclerosing Cholangitis.

Study Overview
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Brief Summary
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Primary objective: To evaluate the efficacy of hymecromone plus standard of care compared with standard of care alone in the treatment of adolescents and adults with primary sclerosing cholangitis (PSC). Secondary objectives: To evaluate the change in Alkaline Phosphatase (ALP) from baseline to 6 months post-treatment following treatment with hymecromone plus standard of care compared with standard of care. To evaluate changes in biomarkers of PSC disease during hymecromone treatment, namely: (a) fibrotic effect (FibroScan); (b) inflammatory biomarkers (serum Hyaluronan (HA)); and, (c) T-cell count.

Official Title
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A Study of Oral Hymecromone to Treat Adolescents and Adults With Primary Sclerosing Cholangitis(HAAPS Study).

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Drug: Hymecromone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of primary sclerosing cholangitis confirmed by liver biopsy and/or imaging study If history of endoscopically confirmed inflammatory bowel disease, currently stable based on Mayo Score / Disease Activity Index (DAI) for Ulcerative Colitis Score ≤ 1, normal inflammatory markers (ESR, CRP and fecal calprotectin) and stable non-excluded medical therapy for at least 6 months Exclusion Criteria: Currently receiving biologic therapies Known allergy to hymecromone Cholangiocarcinoma Pregnancy Serious liver disease

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hymecromone<br>Participants will receive Hymecromone for six months + Standard Of Care (SOC), and will be followed for an additional nine months. | Drug: Hymecromone<br>* Hymecromone 400 mg 3 times daily by mouth.<br>* Other names: Isochol;|
| No Intervention: Standard Of Care (SOC)<br>Participants will receive Standard Of Care (SOC), and will be followed for 15 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum gamma-glutamyltransferase (GGT) levels |  | Baseline to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum Alkaline Phosphatase (ALP) levels |  | Baseline to Month 6 | 
| Change in serum hyaluronan levels |  | Baseline to Month 6 | 
| Change in T-cell count |  | Baseline to Month 6 | 
| Change in fibrotic effect based on FibroScan | Fibrotic effect is the amount of liver with fatty change | Baseline to Month 6 | 
| Change in biliary tree anatomy (e.g. strictures) based on FibroScan |  | Baseline to Month 6 | 
| Change in serum inflammatory cytokine profile | This outcome measure will assess pro-inflammatory cytokines previously associated with biliary inflammation and other autoimmune diseases including IFNg, IL-6, and TNF. | Baseline to Month 6 | 
| Change in lymphocyte immunophenotype | Single cell analysis technique will be used to assess the lymphocytes (B- and T-cells) present in serum samples, including FoxP3+ regulatory T-cells, a tolerogenic lymphocyte subset with important roles in immune tolerance. | Baseline to Month 6 | 
| Plasma drug levels of 4-MU |  | Single blood draw at baseline, week 2, and months 1, 3, and 6 study visits | 
| Plasma drug levels of 4-MUG |  | Single blood draw at baseline, week 2, and months 1, 3, and 6 study visits | 
| Plasma drug levels of 4-MUS |  | Single blood draw at baseline, week 2, and months 1, 3, and 6 study visits |