Comparative PK Assessment Study of Casdatifan in Moderate Hepatically Impaired Participants Versus Matched Participants With Normal Hepatic Function

A Phase 1, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Pharmacokinetics of Casdatifan (AB521) in Participants With Moderate Hepatic Impairment Compared to Healthy Matched Participants

The purpose of the study is to compare the single dose PK of casdatifan between participants with moderate hepatic impairment (HI) and healthy matched control participants with normal hepatic function.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Impairment; Healthy Participants
• Intervention / Treatment: Drug: Casdatifan

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Medical Director; Phone Number: +1-510-462-3330; Email: ClinicalTrialInquiry@arcusbio.com

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

All Participants:

• Male participants must be vasectomized
• BMI ≥ 18.0 and ≤ 42.0 kg/m2 and body weight ≥ 45 kg at screening.

Participants with Moderate HI (Group 1)

• Is classified as having moderate HI by the Child-Pugh classification system (Class B, score of 7 to 9, inclusive) at screening.
• Has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency at screening

Healthy Participants:

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

Exclusion Criteria:

All Participants:

• Participants with Gilbert's syndrome.

Participants with Moderate HI (Group 1):

• Positive for HBsAg or HCV Ab, and detectable viral load at screening.
• Severe complications of liver disease within the preceding 3 months of screening.
• Fluctuating or rapidly deteriorating hepatic function from screening until prior to dosing, in the opinion of the PI or designee.

Healthy Control Participants:

• History or presence of clinically significant medical or psychiatric condition or disease, or presence of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Moderate Hepatic Impairment; Administered as specified in the treatment arm.	Drug: Casdatifan; Participants will receive a 100 mg single oral dose of casdatifan.
Experimental: Group 2: Healthy Control Participants; Administered as specified in the treatment arm.	Drug: Casdatifan; Participants will receive a 100 mg single oral dose of casdatifan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the concentration time curve, from time 0 to the last observed non-zero concentration, of casdatifan in plasma (AUC0-t)	Up to 10 days post-dose
Area under the concentration time curve from time 0 extrapolated to infinity of casdatifan in plasma (AUC0-inf)	Up to 10 days post-dose
Maximum observed concentration of casdatifan in plasma (Cmax)	Up to 10 days post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach Cmax of casdatifan in plasma (Tmax)	Up to 10 days post-dose
Apparent first order terminal elimination rate constant calculated from a semi log plot of the plasma concentration versus time curve (Kel)	Up to 10 days post-dose
Percent of AUC0-inf extrapolated (AUC%extrap)	Up to 10 days post-dose
Apparent first order terminal elimination half life (t½)	Up to 10 days post-dose
Apparent total clearance (CL/F)	Up to 10 days post-dose
Apparent total clearance (Vz/F)	Up to 10 days post-dose
Unbound fraction (fu) of casdatifan	Up to 10 days post-dose
Number of participants experiencing Adverse Events (AEs)	Up to 23 days post-dose

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Investigators: Study Director: Medical Director, Arcus Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: August 3, 2026
• First Submitted That Met QC Criteria: August 3, 2026
• First Posted (Actual): August 7, 2026

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 2, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatic Impairment; AB521; HIF-2α; Casdatifan
• Other Study ID Numbers: ARC-521-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

For more information, please visit our website. URL: https://trials.arcusbio.com/our-transparency-policy

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

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