Golcadomide for Liver Disease

Recruiting at 2 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: Major surgery, ADME conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and metabolism of a drug called golcadomide (BMS-986369) in individuals with liver problems and healthy participants. It includes three groups: one with moderate liver issues, another with severe liver issues, and a healthy group for comparison. The trial seeks participants with ongoing liver conditions, possibly from past alcohol use, who do not have other major health issues. Eligible participants should have a BMI between 18 and 40 and a body weight of at least 50 kg. As a Phase 1 trial, this research aims to understand how golcadomide works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

Is there any evidence suggesting that golcadomide (BMS-986369) is likely to be safe for humans?

Research has shown that golcadomide has been studied for its safety. Some studies have examined its safety when combined with rituximab, helping researchers understand how well people tolerate golcadomide.

The current study is in an early phase, focusing on testing safety and determining the right dose. As a result, detailed safety information is limited. However, the drug's progression in research suggests that earlier results have been promising enough to warrant further testing.

If golcadomide had already been approved for another condition, more would be known about its safety. In this case, the focus is on understanding its effects on liver disease. More information will become available as the study progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for liver disease?

Golcadomide (BMS-986369) is unique because it offers a novel approach to treating liver disease by potentially targeting different degrees of hepatic impairment. Unlike current treatments, which often focus on managing symptoms or slowing disease progression, Golcadomide might work by directly influencing liver function at a molecular level. Researchers are excited about its potential to address both moderate and severe hepatic impairment in a tailored way, which could lead to more effective and personalized treatment plans for patients with varying levels of liver functionality.

What evidence suggests that golcadomide might be an effective treatment for liver disease?

Golcadomide has shown promising results and appears safe in various studies. While its effectiveness for liver disease is still under investigation, it has been tested for other conditions, such as post-CAR T-cell therapy, with positive outcomes. In this trial, participants will be divided into groups based on liver function to study Golcadomide's effects on individuals with varying degrees of hepatic impairment. Researchers are examining its potential to aid conditions requiring immune system support. Golcadomide remains under study to determine its efficacy and safety for individuals with liver issues. Further research will help confirm its effectiveness for liver disease. ^{3 6 7 8 9}

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 moderate to severe liver impairment or cirrhosis, often due to chronic liver disease or past alcohol use. They must have a BMI between 18 and 40 kg/m^2, weigh at least 50 kg, and not have other significant diseases. Healthy individuals with normal liver function are also eligible.

Inclusion Criteria

Participants have moderate (Group A) or severe (Group B) HI as defined by National Cancer Institute-Organ Dysfunction Working Group (NCI-ODWG) criteria.

Participants must have liver-related laboratory test results within the respective reference ranges or with clinically insignificant excursions as agreed by the investigator and the Sponsor Medical Monitor.

Body mass index (BMI) between 18 and 40 kg/m^2 (inclusive), and body weight ≥ 50 kg.

Exclusion Criteria

I have no conditions that could affect how drugs work in my body.

Other protocol-defined Inclusion/Exclusion criteria apply.

I have not had major surgery in the last 8 weeks.

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 Golcadomide (BMS-986369) to assess pharmacokinetics and safety

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Golcadomide (BMS-986369)

Trial Overview The study is testing the drug levels and safety of Golcadomide (BMS-986369) in participants with different degrees of liver impairment compared to healthy controls. It aims to understand how varying levels of liver health affect the drug's behavior in the body.

How Is the Trial Designed?

Group I: Group C: BMS-986369 Normal Hepatic Function Experimental Treatment 1 Intervention

Group II: Group B: BMS-986369 Severe Hepatic Impairment Experimental Treatment 1 Intervention

Group III: Group A: BMS-986369 Moderate Hepatic 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 3-year study involving 77 patients with primary biliary cirrhosis, the combination of budesonide and ursodeoxycholic acid (UDCA) significantly improved liver histology, with 22% of patients showing stage improvement compared to a 20% deterioration in those receiving UDCA alone.

Budesonide and UDCA together led to a 25% decrease in fibrosis and a significant reduction in liver inflammation, while UDCA alone did not show similar histological benefits, indicating that the combination therapy may be more effective for liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. Rautiainen, H., Kärkkäinen, P., Karvonen, AL., et al.[2013]

In a study of 250 Indian patients with intrahepatic cholestasis due to chronic non-alcoholic liver disease, treatment with Heptral (ademetionine) led to significant improvements in symptoms like fatigue, jaundice, and pruritus, as well as reductions in biochemical markers of liver function after six weeks.

The treatment was well tolerated by patients, and physicians reported a favorable opinion on its effectiveness, indicating that Heptral could be a beneficial option for managing intrahepatic cholestasis in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heptral (ademetionine) in patients with intrahepatic cholestasis in chronic liver disease due to non-alcoholic liver disease: results of a multicentre observational study in India. Virukalpattigopalratnam, MP., Singh, T., Ravishankar, AC.[2014]

In a study using bile duct ligation (BDL) rats as a model for primary biliary cholangitis (PBC), golexanolone treatment significantly improved fatigue, cognitive function, and motor coordination, which are commonly impaired in this condition.

The improvements in fatigue and cognitive/motor function were linked to reductions in peripheral inflammation, neuroinflammation, and enhancements in GABAergic neurotransmission in the cerebellum, suggesting a potential therapeutic role for golexanolone in treating symptoms of PBC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation. Arenas, YM., Izquierdo-Altarejos, P., Martinez-García, M., et al.[2023]

Ursodeoxycholic acid treatment for up to 12 years in patients with primary biliary cirrhosis showed significant improvements in symptoms and laboratory markers, particularly in early-stage patients, with 12 out of 13 becoming asymptomatic.

Despite its benefits, ursodeoxycholic acid did not cure the disease or prevent complications associated with cirrhosis, such as variceal hemorrhage and the need for liver transplantation, indicating that while it can improve quality of life, it does not halt disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of ursodeoxycholic acid after 4 to 12 years of therapy in early and late stages of primary biliary cirrhosis. Leuschner, U., Güldütuna, S., Imhof, M., et al.[2019]

Budesonide is an effective first-line treatment for non-severe acute or chronic autoimmune hepatitis, offering a local action with low systemic absorption, which may reduce potential side effects.

The review highlights budesonide's favorable safety profile compared to traditional glucocorticoids like prednisone, making it a recommended alternative for managing autoimmune hepatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide in the first line treatment of patients with autoimmune hepatitis. Olivas, I., Cobreros, M., Londoño, MC., et al.[2022]

Thalidomide significantly improved the heart's response to stimulation in rats with cirrhotic cardiomyopathy, suggesting it may enhance cardiac function in this condition.

The treatment reduced portal pressure and levels of inflammatory markers (NO, TNF-α, IL-6) while increasing the expression of the SOCS1 gene, indicating a potential mechanism for its beneficial effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide attenuates the hyporesponsiveness of isolated atria to chronotropic stimulation in BDL rats: The involvement of TNF-α, IL-6 inhibition, and SOCS1 activation. Hosseini-Chegeni, A., Jazaeri, F., Yousefi-Ahmadipour, A., et al.[2022]

A 58-year-old woman with end-stage plasma cell leukemia developed hepatitis after starting treatment with thalidomide, indicating a potential side effect of this medication.

The patient's liver issues resolved quickly after stopping thalidomide, suggesting that while thalidomide can be effective for certain conditions, it may also pose risks such as hepatotoxicity, especially in patients with pre-existing liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide-associated hepatitis: a case report. Fowler, R., Imrie, K.[2016]

Thalidomide is generally considered a safe and effective treatment for advanced multiple myeloma, but this case highlights that it can cause severe hepatotoxicity, as seen in a 76-year-old woman who experienced a dramatic increase in liver enzymes after 6 weeks of therapy.

The patient's liver function improved significantly after discontinuing thalidomide, indicating that while hepatotoxicity is rare, it is a serious potential side effect that clinicians should monitor, especially as thalidomide use expands.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide-induced severe hepatotoxicity. Hanje, AJ., Shamp, JL., Thomas, FB., et al.[2016]

In a phase II study involving 37 patients with advanced hepatocellular carcinoma (HCC), thalidomide demonstrated modest antitumor activity, with only one patient showing a partial response and 16% achieving stable disease for over 6 months.

Thalidomide was generally well-tolerated, with common side effects including somnolence and fatigue reported in 84% and 73% of patients, respectively, indicating that while it has limited efficacy, it may be a tolerable option for some patients with advanced HCC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-centre phase II trial of Thalidomide in the treatment of unresectable hepatocellular carcinoma. Chuah, B., Lim, R., Boyer, M., et al.[2013]

Thalidomide, commonly used to treat multiple myeloma, has been associated with a case of drug-induced liver injury (DILI), highlighting a potential new side effect as its use expands.

The case presented demonstrates a clear temporal relationship between thalidomide administration and the onset of hepatitis, suggesting a causative link that warrants increased awareness among healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature. Vilas-Boas, F., Gonçalves, R., Sobrinho Simões, M., et al.[2016]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06535399/study-to-assess-drug-levels-and-safety-of-golcadomide-bms-986369-in-healthy-participants-and-participants-with-different-degrees-of-hepatic-impairment

Study to Assess Drug Levels and Safety of Golcadomide ... The purpose of this study is to assess the drug levels and safety of golcadomide (BMS-986369) in adult participants with moderate and severe ...

2. withpower.com withpower.com/trial/phase-1-liver-diseases-7-2024-8d61f

Golcadomide for Liver Disease The purpose of this study is to assess the drug levels and safety of golcadomide (BMS-986369) in adult participants with moderate and severe Hepatic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06271057

NCT06271057 | Golcadomide Post-CAR T-cell in R/R ... The primary objective of the study is to estimate the efficacy of golcadomide administered post-anti-CD19 CAR T-cell infusion, Efficacy determination will be ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124093224

Golseek-1: A Phase 3, Double-Blind, Randomized Study ... The efficacy and safety data observed in early-phase studies suggest promising activity and a manageable safety profile. This supports further investigation ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-golcadomide-for-patients-with-relapsed-or-refractory-aggressive-large-b-cell-lymphoma-at-high-risk-of-relapse-after-car-t-cell-therapy/

Study on Golcadomide for Patients with Relapsed or ... During the study, researchers will look at various outcomes, such as the rate of complete response to the treatment, how long the response lasts, and overall ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/524995

Study to Assess Drug Levels and Safety of Golcadomide (BMS ... The purpose of this study is to assess the drug levels and safety of golcadomide (BMS-986369) in adult participants with moderate and severe Hepatic ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06911502

NCT06911502 | A Study to Compare the Efficacy and ... The study is designed as a multicenter, randomized, open label Phase 3 study to compare the efficacy and safety of golcadomide in combination with rituximab ...

8. dana-farber.org dana-farber.org/clinical-trials/25-477

A Phase 3, Multicenter, Randomized, Open Label Study to ... The study is designed as a multicenter, randomized, open label Phase 3 study to compare the efficacy and safety of golcadomide in combination with rituximab ...

9. bmsclinicaltrials.com bmsclinicaltrials.com/us/en/clinical-trials/NCT06425302

Trial ID CA073-1022 | NCT06425302 - BMS Clinical Trials The purpose of this study is to assess the efficacy and safety of golcadomide in combination with rituximab in participants with newly diagnosed advan