Oral Hymecromone for Primary Sclerosing Cholangitis

(HAAPS Trial)

Recruiting at 1 trial location

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Aparna Goel

Must not be taking: Biologics

Disqualifiers: Cholangiocarcinoma, Pregnancy, Serious liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

24 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but it does require that you are not currently receiving biologic therapies. If you have inflammatory bowel disease, your treatment must be stable for at least 6 months.

What makes the drug Hymecromone unique for treating Primary Sclerosing Cholangitis?

Hymecromone is unique because it is an oral drug that may offer a novel approach to treating Primary Sclerosing Cholangitis, a condition with limited treatment options. Its potential benefits could be related to its known effects in other conditions, such as its anti-inflammatory properties and ability to influence bile acid metabolism. ^{1 2 3 4 5}

Research Team

Aparna Goel, MD

Principal Investigator

Stanford University

Leina Alrabadi, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adolescents and adults with confirmed primary sclerosing cholangitis (PSC). Participants should have stable inflammatory bowel disease if present, normal inflammation markers, and consistent non-excluded medication for at least 6 months. Those on biologics, pregnant individuals, people with serious liver issues or cholangiocarcinoma, or allergies to hymecromone can't join.

Inclusion Criteria

My inflammatory bowel disease is stable, with normal markers and no changes in treatment for 6 months.

My liver condition was confirmed by a biopsy or imaging.

Exclusion Criteria

I have a serious liver condition.

Pregnancy

I have been diagnosed with cholangiocarcinoma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Hymecromone plus Standard Of Care for six months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 months

Treatment Details

Interventions

• Hymecromone

Trial Overview The study tests the effectiveness of hymecromone added to standard care versus standard care alone in treating PSC. It will measure changes in liver enzymes (ALP), fibrosis via FibroScan, serum Hyaluronan levels indicating inflammation, and T-cell counts over a period of six months.

Participant Groups

Group I: Hymecromone Experimental Treatment 1 Intervention

Participants will receive Hymecromone for six months + Standard Of Care (SOC), and will be followed for an additional nine months.

Group II: Standard Of Care (SOC) Active Control 1 Intervention

Participants will receive Standard Of Care (SOC), and will be followed for 15 months.

Hymecromone is already approved in European Union for the following indications:

Approved in European Union as Hymecromone for:

• Biliary spasm

Who Is Running the Clinical Trial?

Aparna Goel

Lead Sponsor

Trials

1

Recruited

20+

Paul Bollyky

Lead Sponsor

Trials

2

Recruited

40+

Findings from Research

The study identified 24 metabolites of chamaechromone in rats, with 20 being novel, highlighting its complex metabolic pathways involving processes like hydroxylation and methylation.

Chamaechromone undergoes extensive Phase I and Phase II metabolism, which is crucial for understanding its safety and efficacy as a potential therapeutic agent, especially given its use in traditional medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolites characterization of chamaechromone in vivo and in vitro by using ultra-performance liquid chromatography/Xevo G2 quadrupole time-of-flight tandem mass spectrometry. Lou, Y., Zheng, J., Wang, B., et al.[2013]

A new compound called sophorophenolone was discovered from the pericarps of Sophorajaponica L., along with 13 other known compounds, indicating the potential for further research into their medicinal properties.

The structure of sophorophenolone was thoroughly characterized using advanced techniques like UV, IR, MS, and various NMR spectroscopy methods, which helps in understanding its chemical properties and potential applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new coumaronochromone from Sophora japonica. Tang, YP., Hu, J., Wang, JH., et al.[2009]

Researchers isolated two new compounds from the roots of Prionosciadium thapsoides, identified as dihydrofurochromones, which could have potential therapeutic applications.

The structures of these new compounds were confirmed using advanced techniques like NMR and X-ray diffraction, ensuring their chemical configurations are accurately understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dihydrofurochromones from Prionosciadium thapsoides. Torres-Valencia, JM., Chávez-Ríos, OE., Cerda-García-Rojas, CM., et al.[2011]

A new compound, 3,3-dimethylallylspatheliachromene methyl ether, was isolated from the plant Dictyoloma vandellianum and showed significant cytotoxic activity against tumor cell lines, with IC50 values between 6.26 and 14.82 μg/ml.

This compound also exhibited a moderate level of cytotoxicity in non-tumor cells (PBMC), with an IC50 value of 11.65 μg/ml, indicating a potential therapeutic window for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pyranochromones from Dictyoloma vandellianum A. Juss and Their Cytotoxic Evaluation. Alves, IM., Abreu, LS., Costa, CO., et al.[2017]

Chamaechromone, found in the roots of Stellera chamaejasme, has been shown to have antihepatitis B virus activity, and its metabolism in the human liver involves specific enzymes that could influence its efficacy.

The study identified key metabolic pathways for chamaechromone, revealing that its hydroxylation is primarily catalyzed by cytochrome P450 1A2 and glucuronidation by several UDP-glucuronosyltransferases, which could affect how the compound is processed in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolism of chamaechromone in vitro with human liver microsomes and recombinant human drug-metabolizing enzymes. Lou, Y., Hu, H., Qiu, Y., et al.[2014]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Metabolites characterization of chamaechromone in vivo and in vitro by using ultra-performance liquid chromatography/Xevo G2 quadrupole time-of-flight tandem mass spectrometry. [2013]

2. England pubmed.ncbi.nlm.nih.gov

A new coumaronochromone from Sophora japonica. [2009]

3. United States pubmed.ncbi.nlm.nih.gov

Dihydrofurochromones from Prionosciadium thapsoides. [2011]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Pyranochromones from Dictyoloma vandellianum A. Juss and Their Cytotoxic Evaluation. [2017]

5. Germany pubmed.ncbi.nlm.nih.gov

Metabolism of chamaechromone in vitro with human liver microsomes and recombinant human drug-metabolizing enzymes. [2014]