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

Trial Summary

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 Golcadomide (BMS-986369) safe for humans?

While Golcadomide itself is not directly mentioned, similar drugs like Thalidomide have been associated with liver issues in some cases, such as hepatitis (liver inflammation) and hepatotoxicity (liver damage). These side effects are rare but can be serious, so it's important to monitor liver function during treatment. ^{1 2 3 4 5}

What makes Golcadomide unique for liver disease treatment?

Golcadomide (BMS-986369) is unique because it is a novel drug that may offer a different mechanism of action compared to existing treatments for liver disease, although specific details about its action in liver disease are not provided in the available research. ^{6 7 8 9 10}

What is the purpose of this trial?

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 Impairment (HI), and in matched healthy control participants with normal hepatic function.

Research Team

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Eligibility Criteria

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.

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

Other protocol-defined Inclusion/Exclusion criteria apply.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Iran 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. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Thalidomide-induced severe hepatotoxicity. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Thalidomide-associated hepatitis: a case report. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Multi-centre phase II trial of Thalidomide in the treatment of unresectable hepatocellular carcinoma. [2013]

5. Spain pubmed.ncbi.nlm.nih.gov

Thalidomide-induced acute cholestatic hepatitis: case report and review of the literature. [2016]

6. Netherlands 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. [2019]

7. Spain pubmed.ncbi.nlm.nih.gov

Budesonide in the first line treatment of patients with autoimmune hepatitis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Budesonide combined with UDCA to improve liver histology in primary biliary cirrhosis: a three-year randomized trial. [2013]

9. India 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. [2014]

10. United States pubmed.ncbi.nlm.nih.gov

Golexanolone improves fatigue, motor incoordination and gait and memory in rats with bile duct ligation. [2023]