Trial Summary
What is the purpose of this trial?There is a significant unmet need for safe and effective therapeutic approaches to prevent immune-mediated graft injury and its complications in liver transplant (LT) recipients with autoimmune liver disease (AILD) including autoimmune hepatitis and primary sclerosing cholangitis. Siplizumab is an anti-cluster of differentiation 2 (CD2) monoclonal antibody that has demonstrated a favorable safety profile of siplizumab in over 779 human subjects and has been shown to target memory T cells-a key driver in the immune processes surrounding rejection and autoimmunity post LT in AILD. The purpose of this pilot, open-label phase 1 study is to determine the safety of siplizumab for induction in patients with AILD undergoing LT.
Up to eight (8) subjects will receive siplizumab 0.6 mg/kg/dose on the day of transplant (Day 0) and Day 4 post-transplant, for a total of two doses.
All subjects will be followed in the study for 12 months post-LT.
Is the drug Siplizumab a promising treatment for autoimmune liver disease?The provided research articles do not mention Siplizumab or its effectiveness for autoimmune liver disease. Therefore, based on the given information, we cannot determine if Siplizumab is a promising treatment for this condition.157810
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you need to stop taking your current medications. However, it excludes those who have used other investigational products in the last 30 days or 5 half-lives, so it's best to discuss your current medications with the trial team.
What safety data is available for Siplizumab (MEDI-507, TCD 601) in autoimmune liver disease?The provided research does not contain specific safety data for Siplizumab (also known as MEDI-507 or TCD 601) in the context of autoimmune liver disease. The studies focus on other biologic agents such as tocilizumab, vedolizumab, and immune checkpoint inhibitors, discussing their potential liver-related adverse effects. To find relevant safety data for Siplizumab, further research specifically targeting this treatment would be necessary.27101112
What data supports the idea that Siplizumab for Autoimmune Liver Disease is an effective treatment?The available research does not provide any data on Siplizumab for Autoimmune Liver Disease. Instead, it focuses on a different drug, Tocilizumab, which is used for conditions like rheumatoid arthritis. There is no information here to support the effectiveness of Siplizumab for Autoimmune Liver Disease.346910
Eligibility Criteria
This trial is for liver transplant recipients with autoimmune liver diseases like autoimmune hepatitis and primary sclerosing cholangitis. Participants should not have other conditions that could interfere with the study or pose a risk.Inclusion Criteria
I have been diagnosed with autoimmune hepatitis or primary sclerosing cholangitis.
I am on the waiting list for a liver transplant.
I am 18 years old or older.
Exclusion Criteria
I am on the waiting list for a multiorgan transplant.
I am experiencing sudden liver failure.
I have been diagnosed with a type of cancer, such as bile duct or liver cancer.
I have an untreated latent TB infection confirmed by a TB blood test.
I have had an organ or tissue transplant.
I have not received a live vaccine within 2 months before my transplant.
I have or had liver disease not related to AIH or PSC.
My organ donor had a non-heart-beating donation or tested positive for hepatitis or had a different blood type.
Treatment Details
The trial tests Siplizumab, an anti-CD2 monoclonal antibody, to see if it's safe and can prevent immune-mediated graft injury post-transplant in patients with AILD. It involves two doses of the drug given around the time of transplant.
1Treatment groups
Experimental Treatment
Group I: Open LabelExperimental Treatment1 Intervention
subjects will receive 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) intraoperatively and on post-transplant Day 4.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Columbia University Irving Medical Center/NewYork-Presbyterian HospitalNew York, NY
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Who is running the clinical trial?
Elizabeth C. VernaLead Sponsor
ITB-Med LLCIndustry Sponsor
References
Autoimmune liver disease. [2023]Autoimmune liver disorders are inflammatory liver diseases characterised histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G (IgG), in the absence of a known etiology. They usually respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. The onset is variable and often mimics acute hepatitis. The previously accepted requirement of six month duration of symptoms before a diagnosis of autoimmune disease could be made has been abandoned.
Tocilizumab: an interleukin-6 receptor inhibitor for the treatment of rheumatoid arthritis. [2016]To review the pharmacology, pharmacokinetics, clinical trial data, and safety profile of tocilizumab, a new biologic agent targeting the interleukin-6 cytokine receptor.
Tocilizumab - a novel therapy for non-organ-specific autoimmune diseases. [2018]In the past decade, tocilizumab, an anti interleukin-6 agent, has been successfully developed as a therapeutic agent for the treatment of rheumatoid arthritis and systemic onset juvenile idiopathic arthritis. In addition to countering inflammation, tocilizumab is also known affect B cell as well as T cell function, thus modulating immune function, and impact osteoclasts, as well as vascular endothelial growth factor. As such, its efficacy is currently being explored in a large number of autoiommune conditions including a number of vasculitides, systemic lupus erythematosus, systemic sclerosis, polymyositis, graft versus host disease, relapsing polychondritis, as well as Behcet's syndrome, spondyloarthropathies, and tumor necrosis factor receptor associated periodic syndrome.
Tocilizumab in patients with active rheumatoid arthritis and inadequate responses to DMARDs and/or TNF inhibitors: a large, open-label study close to clinical practice. [2021]To evaluate the safety and efficacy of tocilizumab in clinical practice in patients with rheumatoid arthritis (RA) with inadequate responses (IR) to disease-modifying antirheumatic drugs (DMARDs) or both DMARDs and tumour necrosis factor α inhibitors (TNFis).
Treatment of autoimmune liver disease: current and future therapeutic options. [2022]Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.
Tocilizumab efficacy and safety in rheumatoid arthritis patients after inadequate response to disease-modifying anti-rheumatic drugs oranti-tumor necrosis factor. [2018]Tocilizumab (TCZ) is a humanized anti-human IL-6R antibody, a novel therapy for rheumatoid arthritis (RA) patients who fail treatment with disease modifying anti-rheumatic drugs (DMARDs) or anti-tumor necrosis factor (anti-TNFs).
Chronic Cholestatic Liver Injury Attributable to Vedolizumab. [2020]Drug-induced liver injury is a rare but clinically important diagnosis. Vedolizumab is an α4β7 integrin inhibitor recently approved for use in patients with moderate-to-severe inflammatory bowel disease. Cases of hepatoxicity due to vedolizumab in the pre-marketing stage were rare, and all cases resolved upon drug withdrawal. We present here the first reported case of hepatotoxicity attributable to vedolizumab, which despite drug cessation persisted with chronic cholestatic liver injury.
[Research advances in autoimmune liver diseases in 2016]. [2018]Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC. This article reviews the research advances in the diagnosis and treatment of autoimmune liver diseases in 2016.
Tocilizumab in the treatment of patients with rheumatoid arthritis in real clinical practice: results of an Italian observational study. [2018]To describe the effectiveness and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, in a cohort of patients with rheumatoid arthritis (RA) recruited in clinical practice.
A case series analysis of serious exacerbations of viral hepatitis and non-viral hepatic injuries in tocilizumab-treated patients. [2021]Reports of moderate to severe liver injury associated with tocilizumab, an interleukin-6 (IL-6) receptor antagonist, have been reported in the post-marketing setting. This case series aims to characterize cases of tocilizumab-associated clinically significant hepatic injury.
Review article: safety of new biologic agents for inflammatory bowel disease in the liver. [2023]New biologic agents (vedolizumab, ustekinumab and tofacitinib) represent an effective treatment for inflammatory bowel diseases and have been recently approved. However, with a rapidly evolving complement of advanced targeted therapies, new concerns about their potentially undesirable effects on liver function emerge. In particular, little is known about safety data in patients with hepatitis B virus, hepatitis C virus chronic infections, cirrhosis and in transplanted patients who are accumulating. In addition, these new agents have also been associated with drug-induced liver injury. Limited data on the efficacy of vedolizumab in patients with primary sclerosing cholangitis are also available. This article reviews available data about hepatic safety concerns in patients receiving vedolizumab, ustekinumab and tofacitinib with and without preexistent hepatic diseases.
Hepatotoxicity in immune checkpoint inhibitors: A pharmacovigilance study from 2014-2021. [2023]Adverse events(AEs) related to hepatotoxicity have been reported in patients treated with immune checkpoint inhibitors (ICIs). As the number of adverse events increases, it is necessary to assess the differences in each immune checkpoint inhibitor regimen. The purpose of this study was to examine the relationship between ICIs and hepatotoxicity in a scientific and systematic manner. Data were obtained from the FDA Adverse Event Reporting System database (FAERS) and included data from the first quarter of 2014 to the fourth quarter of 2021. Disproportionality analysis assessed the association between drugs and adverse reactions based on the reporting odds ratio (ROR) and information components (IC). 9,806 liver adverse events were reported in the FAERS database. A strong signal was detected in older patients (≥65 years) associated with ICIs. hepatic adverse events were most frequently reported with Nivolumab (36.17%). Abnormal liver function, hepatitis, and autoimmune hepatitis were most frequently reported, and hepatitis and immune-mediated hepatitis signals were generated in all regimens. In clinical use, patients should be alert to these adverse effects, especially in elderly patients, who may be aggravated by the use of ICI.