Mezigdomide for Kidney Failure

No longer recruiting at 3 trial locations

Overseen By First line of the email MUST contain NCT# and Site#

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Celgene

Disqualifiers: Chronic pruritus, Malignancy, Oral medication intolerance, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body processes the drug mezigdomide in people with varying kidney health conditions, including severe kidney problems, end-stage renal disease, and normal kidney function. The trial seeks participants who have experienced significant kidney issues impacting daily life and meet specific health criteria, such as maintaining a stable body weight and not having skin problems that could affect results. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that mezigdomide is likely to be safe for humans?

Research has shown that mezigdomide is generally safe for patients who have undergone multiple treatments for other conditions. Studies indicate that while some side effects might occur, they are usually expected and manageable.

For patients with mild to moderate kidney problems, mezigdomide does not appear to worsen their condition, and often, no dosage adjustment is necessary. However, in cases of severe kidney issues, the body may not process the drug as effectively, potentially leading to higher drug levels and an increased risk of side effects.

Overall, the safety profile of mezigdomide appears promising, particularly for those with less severe kidney problems. However, caution is advised for those with severe kidney issues due to potential changes in drug processing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for kidney failure?

Unlike the standard treatments for kidney failure, such as dialysis or transplantation, Mezigdomide offers a new approach by potentially targeting inflammation and immune responses linked to kidney damage. Researchers are excited because Mezigdomide may provide a non-invasive alternative that could slow disease progression without the need for surgical intervention or frequent hospital visits. Additionally, its novel mechanism could address underlying causes of kidney failure, offering hope for improved long-term outcomes for patients.

What evidence suggests that mezigdomide might be an effective treatment for kidney failure?

Research shows that mezigdomide is a promising drug for treating kidney failure, offering a new option for patients who haven't found success with other treatments. Early studies suggest that mild to moderate kidney problems don't alter how mezigdomide works when combined with dexamethasone, a type of steroid. This indicates that people with certain kidney issues might not need to adjust their dose. In this trial, participants will be divided into groups based on kidney function to further investigate its effectiveness. However, more information is needed about its efficacy for severe kidney problems, as research is still ongoing. ^{1 2 4 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for adults with kidney failure who have a BMI between 18.0 and 40.0 kg/m2, weigh at least 50 kg, and don't have a fever. It's not for those with chronic itching or skin conditions that could be confused with drug reactions, anyone unable to take oral meds, or people with a history of cancer except certain treated skin cancers.

Inclusion Criteria

Participants must have a body mass index (BMI) of ≥ 18.0 kg/m2 to ≤ 40.0 kg/m2 inclusive at screening

I do not have a fever (above 100.4°F) at the time of screening or treatment.

I weigh at least 50 kg.

Exclusion Criteria

Other protocol-defined Inclusion/Exclusion criteria apply

I have never had long-term itching or skin conditions that could be confused with medication reactions.

I cannot take medicine by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of Mezigdomide to assess pharmacokinetics

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mezigdomide

Trial Overview The study is looking at how the body processes the drug Mezigdomide in patients who have problems with their kidneys. The focus is on understanding different levels of kidney function and how they affect the medication's presence in the body.

How Is the Trial Designed?

Group I: Group C: Participants with normal renal function Experimental Treatment 1 Intervention

Group II: Group B: Participants with End Stage Renal Disease Experimental Treatment 1 Intervention

Group III: Group A: Participants with severe renal impairment Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Celgene

Lead Sponsor

Trials

649

Recruited

130,000+

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Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

In a phase 2 trial with 288 patients suffering from systemic lupus erythematosus (SLE), iberdomide at a dose of 0.45 mg showed a significant improvement in disease activity response compared to placebo, with 54% of patients achieving an SLE Responder Index (SRI-4) response.

Iberdomide was associated with some adverse events, including urinary tract infections, upper respiratory infections, and neutropenia, indicating the need for further studies to assess its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus. Merrill, JT., Werth, VP., Furie, R., et al.[2022]

Iberdomide, a novel immunomodulatory drug, demonstrated safety and tolerability in a 12-week study involving 42 patients with active systemic lupus erythematosus (SLE), with most side effects being mild to moderate, such as nausea and diarrhea.

The treatment led to significant improvements in disease activity scores, correlating with reductions in specific immune cells, suggesting that iberdomide effectively targets the immune system in SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, ascending-dose, phase 2a study. Furie, RA., Hough, DR., Gaudy, A., et al.[2022]

In a phase 1-2 study involving 178 patients with relapsed and refractory multiple myeloma, the combination of mezigdomide and dexamethasone demonstrated an overall response rate of 41%, indicating promising efficacy for this treatment in heavily pretreated patients.

The most common side effects were neutropenia and infections, which were mostly reversible, suggesting that while the treatment has myelotoxic effects, it does not present unexpected toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. Richardson, PG., Trudel, S., Popat, R., et al.[2023]

CC-220 (compound 6) is a new cereblon modulator that binds more tightly to the cereblon protein than existing drugs lenalidomide and pomalidomide, leading to more effective degradation of the transcription factors Ikaros and Aiolos.

The enhanced binding affinity of CC-220 results in greater cellular degradation of these targets, suggesting it may offer improved therapeutic potential for conditions like systemic lupus erythematosus and relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Cereblon Modulator (CC-220) with Improved Degradation of Ikaros and Aiolos. Matyskiela, ME., Zhang, W., Man, HW., et al.[2021]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

In a study of eight patients with worsening idiopathic membranous nephropathy, a 6-month treatment with alternating prednisolone and chlorambucil significantly reduced proteinuria from an average of 15.3 g/24 h to 2.1 g/24 h (p < 0.05).

The treatment also improved kidney function, with creatinine clearance increasing in six patients and the overall group mean rising from 51.6 ml/min to 81.4 ml/min (p < 0.05), although severe adverse effects from chlorambucil required dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prednisolone and chlorambucil treatment in idiopathic membranous nephropathy with deteriorating renal function. Mathieson, PW., Turner, AN., Maidment, CG., et al.[2019]

In a usability study with 15 patients using the CimplyMe companion app for certolizumab pegol (CZP) self-injection, 86% of critical tasks were successfully completed on the first attempt, indicating the app's effectiveness in supporting self-management of treatment.

All noncritical tasks were completed without errors, suggesting that the app is user-friendly and can help patients manage their treatment without the need for formal training.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Companion App to Support Rheumatology Patients Treated with Certolizumab Pegol: Results From a Usability Study. Domańska, B., Vansant, S., Mountian, I.[2020]

In a study of elderly patients with membranous nephropathy, those treated with mizoribine (MZR) showed a similar remission rate (80%) compared to those treated with prednisolone (PSL) alone (75%), suggesting MZR is an effective alternative for patients who do not respond well to PSL.

Patients in the MZR group required a lower total dose of PSL over one year (5,058 mg) compared to the non-MZR group (6,649 mg), indicating that MZR may help reduce the need for higher doses of corticosteroids while still achieving effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of mizoribine therapy in elderly patients with membranous nephropathy: comparison with patients not receiving mizoribine. Ito, T., Mochizuki, K., Oka, T., et al.[2021]

Membranous nephropathy (MN) is a kidney disease that leads to significant protein loss in urine and can have various causes, with idiopathic cases likely involving immune complex formation that triggers inflammation and damage to kidney cells.

Current treatments for MN, such as corticosteroids and cytotoxic agents, can help induce remission but may have serious side effects; new therapies like rituximab and mycophenolate mofetil show promise, highlighting the need for further research to develop more targeted and effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membranous nephropathy. Ponticelli, C.[2022]

Iberdomide, a potent oral cereblon E3 ligase modulator, was well-tolerated in healthy subjects up to a dose of 6 mg and showed a dose-proportional increase in exposure, with a terminal half-life of 9-13 hours.

The drug demonstrated significant immunomodulatory effects, notably reducing peripheral CD19+ B lymphocytes and proinflammatory cytokines, while also increasing certain T-cell responses, indicating its potential for treating autoimmune and hematological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human, Single- and Multiple-Ascending-Dose Studies in Healthy Subjects to Assess Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability of Iberdomide, a Novel Cereblon E3 Ligase Modulator. Ye, Y., Gaudy, A., Schafer, P., et al.[2022]

A phase 1 study involving 40 subjects with varying degrees of hepatic impairment found that a single 1 mg dose of iberdomide was generally well-tolerated and did not show clinically significant changes in its pharmacokinetics compared to healthy controls.

While the active metabolite M12 showed reduced exposure in subjects with moderate and severe hepatic impairment, these differences were not considered clinically meaningful, indicating that no dose adjustment for iberdomide is necessary in patients with hepatic impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics of Iberdomide in Subjects with Mild, Moderate, or Severe Hepatic Impairment Compared with Healthy Subjects. Cheng, Y., Ye, Y., Gaudy, A., et al.[2023]

Cereblon E3 Ligase Modulating Drugs (CELMoDs) represent a promising new approach in targeted protein degradation, allowing for the modulation of previously undruggable targets.

A suite of assays has been developed to effectively characterize the mechanism of action of CELMoDs, including their ability to induce degradation of specific proteins, which supports the discovery and optimization of these therapeutics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Profiling CELMoD-Mediated Degradation of Cereblon Neosubstrates. Thompson, JW., Clayton, T., Khambatta, G., et al.[2022]

In a study of 92 patients with nephrotic syndrome due to idiopathic membranous nephropathy, combining methylprednisolone with chlorambucil resulted in a significantly higher percentage of patients achieving remission compared to those treated with methylprednisolone alone, especially in the first three years.

While the combination treatment showed better initial results, by the fourth year, the difference in remission rates between the two groups was no longer statistically significant, suggesting that the benefits of adding chlorambucil may diminish over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methylprednisolone plus chlorambucil as compared with methylprednisolone alone for the treatment of idiopathic membranous nephropathy. The Italian Idiopathic Membranous Nephropathy Treatment Study Group. Ponticelli, C., Zucchelli, P., Passerini, P., et al.[2013]

High-dose oral corticosteroids are ineffective for achieving sustained remission or preserving kidney function in patients with membranous nephropathy and should not be used alone (grade A recommendation).

Chlorambucil combined with oral steroids is the preferred treatment for membranous nephropathy, while cyclophosphamide and oral steroids are alternative options, particularly for patients at high risk of progressing to end-stage renal disease (grade A and B recommendations).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of idiopathic membranous nephropathy: evidence-based recommendations. Muirhead, N.[2019]

In a phase 2b study involving 308 adults with systemic lupus erythematosus (SLE), iberdomide significantly reduced B cells and plasmacytoid dendritic cells while increasing regulatory T cells (Tregs) and interleukin 2 (IL-2), indicating its potential to rebalance immune abnormalities in SLE.

Iberdomide demonstrated a strong clinical efficacy in patients with high type I interferon (IFN) expression, significantly decreasing the type I IFN gene signature by 81.5%, which correlates with its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological impact of iberdomide in patients with active systemic lupus erythematosus. Lipsky, PE., Vollenhoven, RV., Dörner, T., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7539

Impact of renal impairment (RI) on pharmacokinetics (PK) ... RI is a common complication in MM and may alter drug elimination, leading to increased systemic exposures, risk of adverse events (AEs), and dosing adjustments.

2. withpower.com withpower.com/trial/phase-1-deteriorating-renal-function-2-2024-32a20

Mezigdomide for Kidney Failure · Info for Participants Mezigdomide is a promising drug for kidney failure because it offers a new approach to treatment, potentially improving outcomes for patients who have not ...

3. researchgate.net researchgate.net/publication/381349944_Impact_of_renal_impairment_RI_on_pharmacokinetics_PK_and_clinical_outcomes_with_mezigdomide_plus_dexamethasone_DEX_in_relapsedrefractory_multiple_myeloma_RRMM

Impact of renal impairment (RI) on pharmacokinetics (PK) ... 55 Mild to moderate renal impairment did not influence clinical outcomes with mezigdomide and dexamethasone, and dose adjustments are likely not required for ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12399888/

The Role of CELMoD Agents in Multiple Myeloma - PMC Mild to moderate renal impairment did not influence clinical outcomes with mezigdomide and dexamethasone, and dose adjustments are likely not ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06048250?term=IDECABTAGENE%20VICLEUCEL&rank=6

Mezigdomide (CC-92480) Post Idecabtagene Vicleucel in ... This phase I trial studies the safety, side effects, best dose and effectiveness of mezigdomide (CC-92480) when given after idecabtagene vicleucel (Abecma ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10583261/

Model based assessment of food and acid reducing agent ... Mezigdomide has demonstrated encouraging clinical activity and a manageable safety profile in heavily pretreated patients with relapsed or ...

7. trial.medpath.com trial.medpath.com/clinical-trial/e86b41c91e68deea/ctis2022-500861-29-00-mezigdomide-carfilzomib-dexamethasone-multiple-myeloma

Phase 3 Study to Evaluate Mezigdomide (CC-92480/BMS ... eGFR will be calculated using the Modification of Diet in Renal Disease (MDRD) formula (see Appendix 8). ... Outcome data and publication updates. Subscribe.