Varegacestat for Liver Disease

Recruiting at 1 trial location

Overseen By Thomas Marbury, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Immunome, Inc.

Disqualifiers: Significant emotional problems, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

44 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is Varegacestat safe for human use?

There is no specific safety data available for Varegacestat in the provided research articles. ^{1 2 3 4 5}

What is the purpose of this trial?

This clinical trial is designed to determine the pharmacokinetics, safety and tolerability of varegacestat in people with impaired liver function compared to people with normal liver function.

Eligibility Criteria

This trial is for adults with diabetic liver disease or other forms of liver impairment, as well as healthy individuals. Participants must have varying degrees of liver function from normal to impaired.

Inclusion Criteria

Medically healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee

Has a score on the Child-Pugh scale at screening visit and confirmed at check-in as follows: Mild: ≥5 and ≤6 [Category A]; or Moderate: ≥7 and ≤9 [Category B]; or Severe: ≥10 and ≤15 [Category C].

Medically healthy, apart from HI, with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs as deemed by the PI or designee

Exclusion Criteria

History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.

History of any illness that, in the opinion of the PI or designee, might confound the results of the study or pose an additional risk to the participant by their participation in the study.

Participants must not be enrolled in the study, if they meet any of the following criteria:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single oral dose of varegacestat on study day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Varegacestat

Trial Overview The study is testing varegacestat to see how the drug behaves in the body (pharmacokinetics), and how safe and tolerable it is for people with different levels of liver health.

Participant Groups

Group I: Treatment Arm Experimental Treatment 1 Intervention

Single oral dose of varegacestat administered on study day 1

Who Is Running the Clinical Trial?

Immunome, Inc.

Lead Sponsor

Trials

7

Recruited

420+

Findings from Research

The FDA's guidance on evaluating drug-induced liver injury (DILI) is effective for most low-risk populations but presents challenges for patients with existing liver diseases, such as viral hepatitis or cancer.

There is a pressing need for clearer guidelines and consensus on liver safety assessments, particularly regarding stopping rules based on ALT levels, to facilitate the approval and use of new antiviral and cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver safety assessment in special populations (hepatitis B, C, and oncology trials). Kullak-Ublick, GA., Merz, M., Griffel, L., et al.[2022]

Thiazolidinediones, like rosiglitazone and pioglitazone, are safer alternatives to the earlier drug troglitazone, which was withdrawn from the market due to severe liver toxicity; the newer drugs have a much lower risk of liver damage, with rare and usually reversible cases reported.

These newer thiazolidinediones may also help reduce liver fat in patients with non-alcoholic steatohepatitis, potentially protecting against serious liver conditions like cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hepatotoxicity of thiazolidinediones. Isley, WL.[2019]

In a study of 38 elderly patients with drug-induced liver injury (DILI), approximately 32.3% of DILI-drug pairs were deemed 'avoidable' using the Liverpool adverse drug reactions avoidability tool (LAAT), indicating potential for prevention strategies.

The findings suggest that a significant portion of DILI cases in this population could be prevented, highlighting the importance of using tools like LAAT for improving patient safety and reducing healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. Danjuma, MI., Almasri, H., Alshokri, S., et al.[2020]

Drug-induced liver injury (DILI) and herb-induced liver injury are increasingly recognized as significant issues, necessitating careful diagnosis and management, particularly through drug discontinuation and therapy reconciliation.

Post-marketing databases are crucial for detecting DILI risks, highlighting the need for improved pre-clinical testing and ongoing surveillance, with a focus on direct oral anticoagulants and herbal supplements as key areas for future research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk. Raschi, E., De Ponti, F.[2020]

A new predictive model using support vector machine (SVM) techniques has been developed to assess the risk of drug-induced liver injury (DILI) based on the physicochemical and structural properties of drug candidates, achieving an average sensitivity and specificity of 70%.

This in silico approach shows promise for early identification of safety alerts in drug development, potentially allowing for better screening of compounds alongside traditional in vitro safety tests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A compound attributes-based predictive model for drug induced liver injury in humans. Liu, Y., Gao, H., He, YD.[2020]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Liver safety assessment in special populations (hepatitis B, C, and oncology trials). [2022]

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

Hepatotoxicity of thiazolidinediones. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. [2020]

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

Drug- and herb-induced liver injury: Progress, current challenges and emerging signals of post-marketing risk. [2020]

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

A compound attributes-based predictive model for drug induced liver injury in humans. [2020]