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

NCT04933747 | Completed Phase 1 FDA Drug

• 1 other identifier: CC-220-CP-008
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 3

Brief 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%).

Conditions

Renal Insufficiency

Keywords

Renal Insufficiency; CC-220; Iberdomide; Phase 1

Outcome Measures

Primary Outcomes (16)

• 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

• 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

• Iberdomide Pharmacokinetics - AUC(INF)

  Estimation of AUC calculated from time zero extrapolated to infinity

  Up to 72 hours following the last dose of iberdomide

• 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

• Iberdomide Pharmacokinetics - Cmax

  Estimation of maximum observed plasma concentration

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - Tmax

  Estimated time to Cmax

  Up to 72 hours following the last dose of iberdomide

• Metabolite M12 Pharmacokinetics - Tmax

  Estimated time to Cmax

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - T-HALF

  Estimation of terminal elimination half-life in plasma

  Up to 72 hours following the last dose of iberdomide

• Metabolite M12 Pharmacokinetics - T-HALF

  Estimation of terminal elimination half-life in plasma

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - CLT/F

  Apparent total plasma clearance when dosed orally

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - CLNR/F

  Apparent nonrenal clearance

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - VZ/F

  Estimation of apparent volume of distribution when dosed orally

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - CLR

  Renal Clearance

  Up to 72 hours following the last dose of iberdomide

• Metabolite M12 Pharmacokinetics - CLR

  Renal clearance

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - UR

  Estimation of amount excreted in urine

  Up to 72 hours following the last dose of iberdomide

• Iberdomide Pharmacokinetics - CLD

  Dialysis clearance

  4 hours post-start of dialysis

Secondary Outcomes (1)

• Incidence of Adverse Events (AEs)

  From enrollment until at least 28 days after completion of the study treatment

Study Arms (3)

Group 1: Participants with severe Renal Impairment (RI)

EXPERIMENTAL

Severe Renal Impairment (RI), as defined by an eGFR \< 30 mL/min/1.73 m2 and not requiring dialysis, at screening

Drug: Iberdomide

Group 2: Participants with kidney failure who are on intermittent hemodialysis (IHD)

EXPERIMENTAL

Kidney failure participants on intermittent hemodialysis (IHD)

Drug: Iberdomide

Group 3: Participants with normal renal function

EXPERIMENTAL

Normal renal function, as defined by a creatinine clearance (Clcr) \> 90 mL/min estimated using the Cockcroft-Gault (C-G) equation, at screening.

Drug: Iberdomide

Interventions

Iberdomide DRUG

Administration of a single oral dose of 1mg iberdomide in participants

Also known as: CC-220

Group 1: Participants with severe Renal Impairment (RI); Group 3: Participants with normal renal function

Eligibility Criteria

• Age: 18 Years - 82 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must satisfy the following criteria to be enrolled in the study:
• Participant is ≥ 18 and ≤ 82 years of age at the time of signing the informed consent form (ICF).
• Participant must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• 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.
• Participant has a body mass index (BMI) ≥ 18 and ≤ 40 kg/m2 at screening.
• Participant has a body weight \> 50 kg at screening.
• Participant is afebrile (febrile is defined as ≥ 38°C or 100.4°F).
• Participants in Group 1 must also satisfy the following criteria to be enrolled in the study:
• 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.
• 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.
• 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.
• 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).
• Participants in Group 2 must also satisfy the following criteria to be enrolled in the study:
• 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.

You may not qualify if:

• The presence of any of the following will exclude a participant from enrollment:
• 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).
• 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.
• Participant has any condition that confounds the ability to interpret data from the study.
• Participant has any surgical or medical condition(s) possibly affecting drug absorption, distribution, metabolism, or excretion
• Participant has any medical or dietary conditions affecting assessment of eGFR or creatinine clearance (not applicable for participants in Group 2).
• Participant is a female of childbearing potential, pregnant, or breastfeeding.
• Participant has donated blood or plasma within 8 weeks prior to the first IP administration.
• Participant has a history of alcohol abuse within 6 months prior to the first IP administration, or positive alcohol screen.
• 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.
• 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.
• 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).
• 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.
• Participant has consumed any medication known to be a strong CYP3A inhibitor within 7 days prior to the first IP administration.
• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (3)

Local Institution - 001

Orlando, Florida, 32809, United States

Location

Local Institution - 002

Knoxville, Tennessee, 37920, United States

Location

Local Institution - 003

San Antonio, Texas, 78215, United States

Location

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency

Interventions

iberdomide

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2021
• First Posted: June 22, 2021
• Study Start: August 12, 2021
• Primary Completion: January 23, 2023
• Study Completion: January 23, 2023
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (3)