Study to Evaluate Safety and Tolerability of Iberdomide (CC-220) in Participants With Kidney Impairment Compared to Participants With Normal Kidney Function

Renal Insufficiency Clinical Trial

Official title:

A Phase 1, Open-label, Multicenter Study to Evaluate the Pharmacokinetics of Iberdomide (CC-220) in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04933747
• Other study ID #: CC-220-CP-008
• Status: Completed
• Phase: Phase 1
• Start date: August 12, 2021
• Est. completion date: January 23, 2023

Study information

• Verified date: February 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label study of iberdomide in participants with severe renal impairment or participants receiving dialysis compared to participants with normal renal function. An open-label design was selected based on the objective nature of the primary endpoints (i.e., Pharmacokinetics parameter estimates based on measurement of iberdomide and M12 concentrations). Participants with severe renal impairment (RI), participants with kidney failure on intermittent hemodialysis (IHD), and participants with normal renal function are being included in the current study. Participants with severe RI and kidney failure participants will be matched to participants with normal renal function based on sex, age (approximately ± 10 years), and body mass index (BMI; approximately ± 30%).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: January 23, 2023
• Est. primary completion date: January 23, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 82 Years

Eligibility

Inclusion Criteria:

Inclusion Criteria for All Participants (All Groups)

Participants must satisfy the following criteria to be enrolled in the study:

1. Participant is = 18 and = 82 years of age at the time of signing the informed consent form (ICF).

2. Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

3. Participant is able to communicate with the Investigator, understand and comply with the requirements of the study, and agree to adhere to restrictions, the study visit schedule, and other protocol requirements, including contraception requirements.

4. Participant has a body mass index (BMI) = 18 and = 40 kg/m2 at screening.

5. Participant has a body weight > 50 kg at screening.

6. Participant is afebrile (febrile is defined as = 38°C or 100.4°F).

Inclusion Criteria for Participants with Severe Renal Impairment (RI) - Group 1

Participants in Group 1 must also satisfy the following criteria to be enrolled in the study:

7. Participant has a supine systolic blood pressure (BP) = 90 and = 180 mm Hg, supine diastolic BP = 60 and = 110 mm Hg, and pulse rate = 40 and = 110 beats per minute.

8. Participant has severe renal impairment as defined by an eGFR < 30 mL/min/1.73 m2 (and not requiring dialysis) at screening. The eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) equation.

9. Participant must be medically stable for at least 1 month before the first IP administration with a clinically acceptable medical history, physical examination (PE), clinical laboratory safety test results, vital sign measurements, and 12-lead electrocardiograms (ECGs) consistent with the underlying stable RI condition, as judged by the Investigator.

a. Participant must have a QTcF value < 480 ms.

10. Participant must be stable in concomitant medication regimen (defined as not starting a new medication[s] or a change in the dosage or frequency of the concomitant medication[s] within 7 days or 5 half-lives [whichever is longer] before the first IP administration).

Inclusion Criteria for Participants with Kidney Failure on IHD - Group 2

Participants in Group 2 must also satisfy the following criteria to be enrolled in the study:

11. Participant has a pulse rate = 40 and = 110 beats per minute. Blood pressure measurements must be consistent with the participant's underlying medical condition(s) and judged by the Investigator as being clinically acceptable for purposes of study entry.

12. Participant must be medically stable for at least 1 month before the first IP administration with a clinically acceptable medical history, PE, clinical laboratory safety test results, vital sign measurements, and 12-lead ECGs consistent with the underlying kidney failure, as judged by the Investigator.

13. Participant must be stable in concomitant medication regimen

14. Participant has been attending an average of 3 hemodialysis treatments per week within the 3 months prior to screening.

Inclusion Criteria for Participants with Normal Renal Function -Group 3

15. Participant has a supine systolic BP = 90 and = 160 mm Hg, supine diastolic BP = 50 and = 100 mm Hg, and pulse rate = 40 and = 100 beats per minute.

16. Participant is in good health, as determined by past medical history, PE, vital signs, 12-lead ECG, and clinical laboratory safety test results, and has normal renal function, as defined by having a Clcr > 90 mL/min estimated using the C-G equation, at screening.

1. If male, participant has a QTcF value < 470 ms;

2. If female, participant has a QTcF value < 480 ms.

17. Participant must match at least 1 participant in Groups 1 or 2 with respect to sex, age (approximately ± 10 years), and BMI (approximately ± 30%).

Exclusion Criteria:

Exclusion Criteria for All Participants (All Groups)

The presence of any of the following will exclude a participant from enrollment:

1. Participant has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the participant from participating in the study (excluding stable renal impairment and associated comorbidities for participants in Groups 1 and 2).

2. Participant has any condition, including active or uncontrolled infection and/or the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.

3. Participant has any condition that confounds the ability to interpret data from the study.

4. Participant has any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, or excretion

5. Participant has any medical or dietary conditions affecting assessment of eGFR or creatinine clearance (not applicable for participants in Group 2).

6. Participant is a female of childbearing potential, pregnant, or breastfeeding.

7. Participant has donated blood or plasma within 8 weeks prior to the first IP administration.

8. Participant has a history of alcohol abuse within 6 months prior to the first IP administration, or positive alcohol screen.

9. Participant has history of drug abuse within 6 months prior to the first IP administration, or positive drug screen that is not consistent with the participant's prescribed medication and/or medical history.

10. Participant is known to have serum hepatitis; known to be a carrier of the hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc); - have a positive result to the test for hepatitis B or hepatitis C virus (positive viral ribonucleic acid (RNA) titer for hepatitis C) at screening or have a positive result to the test for human immunodeficiency virus (HIV) antibodies at screening. Positive anti-HBc results may be further qualified with a hepatitis B virus (HBV) DNA test; subjects with non-detectable HBV levels may be included at the discretion of the Investigator.

11. Participant has been exposed to an investigational drug (new chemical entity) within 30 days prior to the first IP administration, or 5 half-lives of that investigational drug, if known (whichever is longer).

12. Participant has consumed any medication known to be a strong CYP3A inducer (including St. John's wort) within 30 days prior to the first IP administration.

13. Participant has consumed any medication known to be a strong CYP3A inhibitor within 7 days prior to the first IP administration.

14. Participant has consumed grapefruit, grapefruit juice, or any other grapefruit-containing product or oranges, orange juice, or any other product containing and/or made from oranges within 7 days prior to the first IP administration.

15. Participant smokes more than 10 cigarettes per day, or the equivalent in other tobacco products (self-reported).

16. Participant is part of the clinical site staff personnel or a family member of the clinical site staff.

17. Participant has received immunization with a live or live attenuated vaccine within 30 days prior the first IP administration or is planning to receive immunization with a live or live attenuated vaccine within 30 days following administration of the last dose of IP.

18. Participant has a history of multiple drug allergies or drug-related anaphylaxis.

Exclusion Criteria for Participants with Severe Renal Impairment and Participants with Kidney Failure on IHD - Groups 1 and 2

The presence of any of the following will also exclude a participant from enrollment:

19. Participant has any serious and/or unstable medical condition occurring within 3 months prior to screening (excluding stable renal impairment and associated comorbidities) with complete resolution of any symptoms and no sequelae that would place the participant at a higher risk from receiving IP, based on Investigator assessment in consultation with the Medical Monitor.

20. Participant has any clinically significant laboratory abnormality not related to renal impairment and related complications.

21. Participant has a history of renal transplant.

a. Participants who had a renal transplant approximately > 2 years which is no longer functioning are allowable.

Exclusion Criteria for Participants with Normal Renal Function - Group 3

The presence of any of the following will also exclude a participant from enrollment:

22. Participant has used any prescribed systemic or topical medication within 30 days prior to the first dose administration.

23. Participant has used any non-prescribed systemic or topical medication within 14 days prior to the first dose administration.

Related Conditions & MeSH terms

• Renal Insufficiency

Intervention

Drug:
• Iberdomide
Administration of a single oral dose of 1mg iberdomide in participants
• Iberdomide
Administration of a single oral dose of 1mg iberdomide in participants on 2 occasions - once on a dialysis day and once on a non-dialysis day

Locations

Country	Name	City	State
United States	Local Institution - 002	Knoxville	Tennessee
United States	Local Institution - 001	Orlando	Florida
United States	Local Institution - 003	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Iberdomide Pharmacokinetics - AUC(0-T)	Estimation of area under the plasma concentration -time curve (AUC) calculated from time zero to time t, where t is the time point of the last measurable concentration	Up to 72 hours following the last dose of iberdomide
Primary	Metabolite M12 Pharmacokinetics - AUC(0-T)	Estimation of AUC calculated from time zero to time t, where t is the time point of the last measurable concentration	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - AUC(INF)	Estimation of AUC calculated from time zero extrapolated to infinity	Up to 72 hours following the last dose of iberdomide
Primary	Metabolite M12 Pharmacokinetics - AUC(INF)	Estimation of AUC calculated from time zero extrapolated to infinity	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - Cmax	Estimation of maximum observed plasma concentration	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - Tmax	Estimated time to Cmax	Up to 72 hours following the last dose of iberdomide
Primary	Metabolite M12 Pharmacokinetics - Tmax	Estimated time to Cmax	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - T-HALF	Estimation of terminal elimination half-life in plasma	Up to 72 hours following the last dose of iberdomide
Primary	Metabolite M12 Pharmacokinetics - T-HALF	Estimation of terminal elimination half-life in plasma	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - CLT/F	Apparent total plasma clearance when dosed orally	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - CLNR/F	Apparent nonrenal clearance	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - VZ/F	Estimation of apparent volume of distribution when dosed orally	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - CLR	Renal Clearance	Up to 72 hours following the last dose of iberdomide
Primary	Metabolite M12 Pharmacokinetics - CLR	Renal clearance	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - UR	Estimation of amount excreted in urine	Up to 72 hours following the last dose of iberdomide
Primary	Iberdomide Pharmacokinetics - CLD	Dialysis clearance	4 hours post-start of dialysis
Secondary	Incidence of Adverse Events (AEs)	An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values), regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE	From enrollment until at least 28 days after completion of the study treatment

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting
•   FDA Safety Alerts and Recalls