A Study to Evaluate CC-486/Onureg in Participants With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Participants With Myeloid Malignancies

A Phase 1, Multicenter, Open-label Study to Evaluate the Pharmacokinetics of CC-486 (Onureg®) in Subjects With Moderate or Severe Hepatic Impairment Compared With Normal Hepatic Function in Adult Subjects With Myeloid Malignancies

The purpose of this study is to evaluate the effect of moderate or severe liver impairment on the drug levels of oral azacitidine and the safety and tolerability of oral azacitidine in participants with myeloid malignancies.

Study Overview

• Status: Terminated
• Conditions: Hepatic Insufficiency; Neoplasms
• Intervention / Treatment: Drug: Onureg

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1426
    • Local Institution - 0012
  • Buenos Aires
    • Pilar, Buenos Aires, Argentina, 1629
      • Local Institution - 0011
  • Buenos Aires F.D.
    • ABB, Buenos Aires F.D., Argentina, C1199ABB
      • Local Institution - 0010
    • Buenos Aires, Buenos Aires F.D., Argentina, C1118AAT
      • Local Institution - 0014
• Colombia
  • Bogota D.C.
    • Bogotá, Bogota D.C., Colombia, 110131
      • Local Institution - 0085
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia, 111151
      • Local Institution - 0084
  • Santander Department
    • Piedecuesta, Santander Department, Colombia, 681017
      • Local Institution - 0086
• Germany
  • Hamburg, Germany, 20246
    • Local Institution - 0074
  • Bavaria
    • Augsburg, Bavaria, Germany, 86156
      • Local Institution - 0076
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Local Institution - 0075
• Spain
  • Salamanca, Spain, 37007
    • Local Institution - 0078
  • Barcelona [Barcelona]
    • Badalona, Barcelona [Barcelona], Spain, 08916
      • Local Institution - 0018
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Local Institution - 0017
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Local Institution - 0015
• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Local Institution - 0083
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Local Institution - 0069
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Local Institution
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Local Institution - 9003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented diagnosis of Myelodysplastic syndrome, Acute myeloid leukemia, Non-acute promyelocytic leukemia, Chronic myelomonocytic leukemia, Philadelphia-negative myeloproliferative neoplasms, Myelodysplastic syndrome Myeloproliferative neoplasms overlap, Accelerated phase and blast phase Myeloproliferative neoplasms, Blastic plasmacytoid dendritic cell neoplasm according to the World Health Organization (WHO) 2016 classification
• Life expectancy of ≥ 3 months
• Stable renal function without dialysis for at least 2 months prior to investigational product administration
• Has moderate or severe hepatic impairment as defined by National Cancer Institute Organ Dysfunction Working Group criteria

Exclusion Criteria:

• Chemotherapy or radiotherapy within 2 weeks or 5 half-lives, whichever is longer, prior to the first day of investigational product administration
• Persistent, clinically significant non-hematologic toxicities from prior therapies which have not recovered to < Grade 2
• Any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study
• History of inflammatory bowel disease, celiac disease, prior gastrectomy, gastric bypass, upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption of the investigational product and/or predispose the participant to an increased risk of gastrointestinal toxicity

Other protocol-defined inclusion/exclusion criteria 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2	Drug: Onureg; Specified dose on specified days; Other Names: CC-486, Oral Azacitidine
Experimental: Group 1	Drug: Onureg; Specified dose on specified days; Other Names: CC-486, Oral Azacitidine
Other: Group 3; Control - participants with normal hepatic function	Drug: Onureg; Specified dose on specified days; Other Names: CC-486, Oral Azacitidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-t: Estimation of area under the plasma concentration-time curve (AUC) calculated from time zero to the last measured time point	Day 1
AUC0-∞: Estimation of AUC calculated from time zero to infinity	Day 1
Cmax: Observed maximum concentration	Day 1

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events	Up to 9 Months
Incidence of serious adverse events	Up to 9 Months
Number of participants with clinically significant changes in electrocardiogram parameters	Up to 9 Months
Incidence of clinically significant changes in vital signs: Body temperature	Up to 9 Months
Incidence of clinically significant changes in vital signs: Respiratory rate	Up to 9 Months
Incidence of clinically significant changes in vital signs: Blood pressure	Up to 9 Months
Incidence of clinically significant changes in vital signs: Heart rate	Up to 9 Months
Incidence of clinically significant changes in clinical laboratory results: Hematology tests	Up to 9 Months
Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests	Up to 9 Months
Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests	Up to 9 Months
Number of Participants with clinically significant changes in Eastern Cooperative Oncology Group (ECOG) performance status	Up to 9 Months
Incidence of clinically significant changes in clinical laboratory results: Liver Function tests	Up to 9 Months
Number of clinically significant changes in physical examinations	Up to 9 Months
Number of participants with a recording of concomitant medications	Up to 9 Months
Number of participants with a recording of concomitant procedures	Up to 9 Months

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2024
• Primary Completion (Actual): April 20, 2025
• Study Completion (Actual): April 20, 2025

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: January 13, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Azacitidine; Hepatic Impairment; Myeloid Malignancies; CC-486; Onureg
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Neoplasms; Hepatic Insufficiency; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Aza Compounds; Nucleosides; Ribonucleosides; Azacitidine; cc-486
• Other Study ID Numbers: CA055-001

Drug and device information, study documents

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