Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a multi-center, open-label study to assess the PK of single 100 mg oral doses of
enasidenib (CC-90007) in subjects with mild, moderate, and severe hepatic impairment (HI),
and in matched healthy control subjects with normal hepatic function.
Degrees of hepatic impairment will be determined during screening by the subject's score
according to Pugh's Modification of Child's Classification of Severity of Liver Disease.
Subjects will be enrolled in 4 Groups as follows:
- Group A: Approximately 8 subjects with mild hepatic impairment (with a Child-Pugh score
of < 7) will be enrolled in Group A.
- Group B: Approximately 8 subjects with moderate hepatic impairment (with a Child-Pugh
score of ≥ 7 to ≤ 9) will be enrolled in Group B.
- Group C: Approximately 8 subjects with severe hepatic impairment (with a Child-Pugh
score of ≥ 10 to ≤ 15) will be enrolled in Group C.
- Group D: Approximately 8-24 healthy subjects with normal hepatic function will be
enrolled in Group D. Subjects in Group D will be matched to subjects in Groups A-C with
respect to sex, age (± 10 years), and weight (± 30 pounds). More than 1 subject with
differing degrees of HI can be matched to a single control; however, all subjects with
HI must be matched to at least 1 healthy match subject.
Phase
Phase 1
Funding Agency/Sponsor
Industry
Disease
Other
Enrollment Eligibility
Inclusion Criteria:
Inclusion Criteria for all subjects (Groups A, B, C, D) Each subject must satisfy all of
the following criteria to be enrolled in the study.
1. Subject must understand and voluntarily sign an informed consent form (ICF) prior to
any study-related assessments/procedures being conducted.
2. Subject is able to communicate with the Investigator, understand and comply with the
requirements of the study, and agree to adhere to restrictions and examination
schedules and other protocol requirements.
3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements, including the restrictions.
4. 4. Male, or non-pregnant and non-nursing female between ≥ 40 and ≤ 75 years of age the
time of signing the ICF..
5. Body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
6. Supine systolic blood pressure (BP): 90 to 160 mmHg, supine diastolic BP:50 to 100
mmHg, and pulse rate: 40 to 100 bpm.
7. Subject is afebrile.
8. Female subjects NOT of childbearing potential must:
a. Have been surgically sterilized at least 6 months before screening, or be naturally
postmenopausal.
9. Females of childbearing potential (FCBP) must have a negative pregnancy test at
Screening and Baseline Visits. While receiving IP and for at least 2 months after
taking the last dose of IP, FCBP who engage in activity in which conception is
possible must use one of the approved contraceptive options.
10. Male subjects must:
1. Practice true abstinence or
2. agree to use a barrier method of birth control during sexual contact with a
pregnant female or FCBP while participating in the study, during dose
interruptions, and for at least 2 months after the last dose of IP, even if he
has undergone a successful vasectomy.
Inclusion Criteria for Subjects with mild, moderate, or severe hepatic impairment
(Groups A-C)
Each subject with mild, moderate, or severe hepatic impairment must also meet all the
applicable criteria listed below for study entry:
11. Subject has moderate or severe hepatic impairment or cirrhosis due to chronic hepatic
disease and/or prior alcohol use.
12. Subject has mild (Group A), moderate (Group B), or severe (Group C) hepatic impairment
as defined by Child-Pugh Score.
1. Group A subjects must have mild hepatic impairment and are required to have
documentary confirmation of the diagnosis of cirrhosis made by biopsy,
laparoscopy, or imaging study with a Child-Pugh score of < 7, at screening.
2. Group B subjects must have moderate hepatic impairment and are required to have
documentary confirmation of the diagnosis of cirrhosis made by biopsy,
laparoscopy, or imaging study with a Child-Pugh score of ≥ 7 to ≤ 9, at
screening.
3. Group C subjects must have severe hepatic impairment. If biopsy or laparoscopy is
not performed prior to screening, subject can be included only if they have
chronic liver disease and objective evidence of portal hypertension (ascites
diagnosis by imaging or varices), or current medication for consequences of
portal hypertension.
In either case a Child-Pugh score of ≥ 10 to ≤ 14 at screening is required. Subjects
should be enrolled into the group corresponding to the Child-Pugh classification score
that most accurately reflects the most severe hepatic disease classification within
the past 6 months (based on past medical history or physical examination observation).
13. Must be medically stable for at least 1 month before screening with clinically
acceptable medical history, PE, clinical laboratory tests, vital signs, and 12-lead
ECGs consistent with the underlying stable mild (Group A), moderate (Group B), or
severe (Group C) hepatic impairment condition, as judged by the Investigator.
14. Subject has a normal or clinically acceptable 12-lead ECG at screening. In addition:
• Subject (male or female) has a QTcF value ≤ 500 msec at screening.
15. Must be stable on a concomitant medication regimen before dosing with study drug).
16. Subjects may be treated with diuretics for ascites; however, subjects with severe
ascites at time of enrollment may only be included at the discretion of the
investigator with agreement of the Sponsor.
17. Subjects may have a history of encephalopathy; however, they must be on stable
treatment for at least 1 month prior to screening, and must not have had an acute
encephalopathic episode in the 1 months prior to screening.
Inclusion Criteria for a Matched Healthy Subject (Group D)
Each matched healthy subject must also meet all applicable criteria listed below for
study entry:
18. Subject must be free of any clinically significant disease that would interfere with
the study evaluations.
19. Subject must have liver-related laboratory test results within the respective
reference ranges or with clinically insignificant excursions therefrom as agreed by
the Investigator.
20. Subject in Group D must match at least one subject in Groups A-C, as needed with
respect to sex, age (± 10 years), and weight (± 30 pounds).
21. Subject must be in good health as determined by past medical history, PE, vital signs,
ECG, and clinical laboratory safety tests. Clinical laboratory safety tests (ie,
hematology, chemistry, and urinalysis) and 12-lead ECGs must be within normal limits
or clinically acceptable as judged by the Investigator.
22. Subject has a normal or clinically acceptable 12-lead ECG at screening. In addition:
23. If male, subject has a QTcF value ≤ 450 msec at screening;
24. If female, subject has a QTcF value ≤ 470 msec at screening.
Exclusion Criteria:
Exclusion Criteria for all Subjects (Group A, B, C, and D) The presence of any of the
following will exclude a subject from enrollment.
1. Subject has any condition or circumstance that prevents the subject from understanding
and signing the ICF.
2. Subject has any condition that places the subject at an unacceptable risk from
participating in the study or would confound the ability to interpret data from the
study.
3. Subject has any significant medical condition or psychiatric illness that would
prevent the subject from participating in the study at Investigator discretion.
4. Subject has any surgical or medical condition(s) possibly affecting drug absorption,
distribution, metabolism, excretion, eg, bariatric procedure. Subjects with
cholecystectomy and appendectomy may be included.
a. Subject has an estimated creatinine clearance < 60 mL/min as calculated using the
Cockcroft-Gault formula- at screening and baseline (Day -1).
5. Subject is pregnant or is breastfeeding.
6. Subject participated in Study CC-90007-CP-003.
7. Subject donated blood or plasma within 2 weeks before dose administration to a blood
bank or blood donation center.
8. Subject has a history of alcohol abuse within 6 months before the first dose
administration, or positive alcohol screen.
9. Subject has a history of drug abuse within 6 months before the first dose
administration, or positive drug screen that is not consistent with the patient's
prescribed medication and or/medical history.
10. Subject is known to have active serum hepatitis, or have a positive result to the test
for Human immunodeficiency virus (HIV) antibodies at screening.
• Chronic or resolved Hepatitis B or Hepatitis C are acceptable only if sequelae are
limited to hepatic involvement and its consequent comorbidities. (ie, Vasculitis,
clinically significant cryoglobulinemia, etc. are unacceptable.)
11. Subject was exposed to an investigational drug within 30 days before dosing, or 5
half-lives of that investigational drug, if known (whichever is longer).
12. Subject used approved medications or herbal medicines that are moderate or strong
cytochrome P450 (CYP)1A2, CYP2B6 CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5
inducers and/or inhibitors (including St. John's wort) within 14 days or 5 half-lives
of screening, whichever is longer.
13. Subject will have consumed Seville oranges, grapefruit or grapefruit juice and/or
pomelos, exotic citrus fruits, or grapefruit hybrids within 14 days or 5 half-lives of
dosing, whichever is longer.
14. Subject smokes more than 10 cigarettes per day, or the equivalent in other tobacco
products (self-reported).
15. Subject has a history of multiple drug allergies or drug-related anaphylaxis.
16. Subject has received live vaccination (excluding seasonal flu vaccination) within 90
days of dosing.
17. Subject is part of the staff personnel or a family member of the investigational study
staff.
18. Subject is, for any reason, deemed by the investigator to be inappropriate for this
study, including a subject who is unable to communicate or to cooperate with the
investigator or the clinical staff.
19. Subject has had a Transjugular intrahepatic portosystemic shunt (TIPS) procedure.
20. Positive SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) test or
signs/symptoms of COVID-19 (Coronavirus Disease 2019) infection.
21. Participants currently in other interventional trials, including those for COVID-19,
may not participate in BMS clinical trials until the protocol specific washout period
is achieved. If a study participant has received an investigational COVID-19 vaccine
or other investigational product designed to treat or prevent COVID-19 prior to
screening, enrollment must be delayed until the biologic impact of the vaccine or
investigational product is stabilized, as determined by discussion between the
Investigator and the Medical Monitor.
Exclusion Criteria for Subjects with Hepatic Impairment (Group A, B, and C) The
presence of any of the following will exclude a hepatically impaired subject from
enrollment.
22. Subject has any unstable medical condition occurring within 3 months prior to signing
the ICF (excluding hepatic impairment and associated comorbidities per Investigator
discretion).
23. Subject has any serious medical condition (excluding hepatic impairment and related
complications), clinically significant laboratory abnormality not related to hepatic
impairment and related complications, or psychiatric illness that would prevent the
subject from signing the ICF and participating in the study per Investigator
discretion.
24. Subject has hepatic encephalopathy with time- or place- disorientation, somnolence,
stupor, rigidity, coma, no personality/behavior, rigidity, or hyperactive reflexes -
or has had such within 1 month of screening.
25. Subject has a history of incipient/planned liver transplantation within 6 months of
screening or has received a liver transplant.
26. Subject has a history of hepatorenal syndrome or hemolysis.
Exclusion Criteria for a Matched Healthy Subject (Group D) The presence of any of the
following will exclude a healthy match subject from enrollment.
27. Subject has any clinically significant laboratory abnormality that in the opinion of
the Investigator, is considered to prevent the subject from safely completing the
study.
28. Subject has any unstable clinically significant illness within 3 months prior to the
study.
29. Subject has any significant medical condition, laboratory abnormality, or psychiatric
illness that would prevent the subject from participating in the study.
30. Positive testing for any active hepatitis, or history of Hepatitis B or C.