Eltrekibart for Hidradenitis Suppurativa
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Eli Lilly and Company
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing a new medication called eltrekibart to find the most effective treatment for adults with moderate-to-severe hidradenitis suppurativa. The goal is to see if it can safely and effectively reduce symptoms by targeting inflammation pathways.
Is the drug Eltrekitibart a promising treatment for hidradenitis suppurativa?The information provided does not mention Eltrekitibart or its effects on hidradenitis suppurativa, so we cannot determine if it is a promising treatment based on the given data.26789
What safety data is available for Eltrekibart in treating Hidradenitis Suppurativa?The provided research does not contain specific safety data for Eltrekibart (also known as Eltrekitibart, LY3041658, or CXCR1/2L mAb) in the treatment of Hidradenitis Suppurativa. The studies mentioned focus on other treatments such as Fostamatinib, Risankizumab, and Povorcitinib, but do not provide safety data for Eltrekibart.347910
What data supports the idea that Eltrekibart for Hidradenitis Suppurativa is an effective treatment?The available research does not provide specific data on the effectiveness of Eltrekibart for Hidradenitis Suppurativa. Instead, it discusses other treatments like Fostamatinib and Janus kinase inhibitors, which have shown some effectiveness in clinical trials. For example, Fostamatinib showed a 75% clinical response in a trial, and Janus kinase inhibitors are noted for reducing inflammation associated with the condition. Without specific data on Eltrekibart, it's unclear how it compares to these treatments.145910
Do I need to stop my current medications for this trial?The trial protocol does not specify if you need to stop your current medications. However, it does require that you agree to use topical antiseptics daily.
Eligibility Criteria
Adults with moderate-to-severe hidradenitis suppurativa (HS) for at least a year, lesions in two areas with one being Hurley Stage II/III, and an inadequate response to oral antibiotics can join. Those with over 20 draining fistulae, recent HS surgery, other skin conditions that could affect HS assessment, active infections or compromised immunity cannot participate.Inclusion Criteria
I have HS lesions in 2 different body areas, with at least one being moderate to severe.
I did not improve or couldn't tolerate a month-long course of antibiotics.
I agree to use skin cleaners daily.
Exclusion Criteria
I have a skin condition that might affect HS assessment.
I currently have or recently had a serious infection.
Treatment Details
The trial is testing Eltrekibart's safety and effective dose against a placebo in adults with HS. Participants will be randomly assigned to receive either the drug or placebo for about 62 weeks across potentially 31 visits to determine the best dosage frequency for further studies.
4Treatment groups
Experimental Treatment
Placebo Group
Group I: Eltrekibart Dose 3Experimental Treatment1 Intervention
Eltrekibart will be given SC.
Group II: Eltrekibart Dose 2Experimental Treatment1 Intervention
Eltrekibart will be given SC.
Group III: Eltrekibart Dose 1Experimental Treatment1 Intervention
Eltrekibart will be given subcutaneously (SC).
Group IV: PlaceboPlacebo Group1 Intervention
Placebo will be given.
Find a clinic near you
Research locations nearbySelect from list below to view details:
Revival Research Institute - TroyTroy, MI
Washington University School of MedicineSaint Louis, MO
International Clinical Research - Tennessee LLCMurfreesboro, TN
University Hospitals Cleveland Medical CenterCleveland, OH
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Who is running the clinical trial?
Eli Lilly and CompanyLead Sponsor
References
Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group. [2020]Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.
Alterations in innate immunity and epithelial cell differentiation are the molecular pillars of hidradenitis suppurativa. [2021]The large unmet need of hidradenitis suppurativa/acne inversa (HS) therapy requires the elucidation of disease-driving mechanisms and tissue targeting.
Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis. [2022]Hidradenitis suppurativa (HS) is a debilitating chronic inflammatory skin disease characterized by chronic abscess formation and development of multiple draining sinus tracts in the groin, axillae, and perineum. Using proteomic and transcriptomic approaches, we characterized the inflammatory responses in HS in depth, revealing immune responses centered on IFN-γ, IL-36, and TNF, with lesser contribution from IL-17A. We further identified B cells and plasma cells, with associated increases in immunoglobulin production and complement activation, as pivotal players in HS pathogenesis, with Bruton's tyrosine kinase (BTK) and spleen tyrosine kinase (SYK) pathway activation as a central signal transduction network in HS. These data provide preclinical evidence to accelerate the path toward clinical trials targeting BTK and SYK signaling in moderate-to-severe HS.
Janus kinase 1 inhibitor INCB054707 for patients with moderate-to-severe hidradenitis suppurativa: results from two phase II studies. [2022]Janus kinase (JAK)-mediated cytokine signalling contributes to local and systemic inflammation in hidradenitis suppurativa (HS).
Dysregulated CD38 expression in blood and skin immune cells of patients with hidradenitis suppurativa. [2023]Hidradenitis suppurativa (HS) is a multifactorial, inflammatory skin disease. Increased systemic inflammatory comorbidities and serum cytokines highlight systemic inflammation as a feature of HS. However, the specific immune cell subsets contributing to systemic and cutaneous inflammation have not been resolved. Here, we generated whole-blood immunomes by mass cytometry. We performed a meta-analysis of RNA-seq data, immunohistochemistry, and imaging mass cytometry to characterize the immunological landscape of skin lesions and perilesions from patients with HS. Blood from patients with HS exhibited lower frequencies of natural killer cells, dendritic cells, and classical (CD14+CD16-) and nonclassical (CD14-CD16+) monocytes, as well as higher frequencies of Th17 cells and intermediate (CD14+CD16+) monocytes than blood from healthy controls. Classical and intermediate monocytes from patients with HS had increased expression of skin-homing chemokine receptors. Furthermore, we identified a CD38+ intermediate monocyte subpopulation that was more abundant in the immunome of blood from patients with HS. Meta-analysis of RNA-seq data found higher CD38 expression in lesional HS skin than in perilesional skin, and markers of classical monocyte infiltration. Imaging mass cytometry showed that CD38+ classical monocytes and CD38+ monocyte-derived macrophages were more abundant in lesional HS skin. Overall, we report targeting CD38 may be worth pursuing in clinical trials.
Efficacy and Safety of Risankizumab for the Treatment of Hidradenitis Suppurativa: A Phase 2, Randomized, Placebo-Controlled Trial. [2023]Hidradenitis suppurativa (HS) is a chronic, immune-mediated skin condition characterized by inflammatory lesions that can cause pain, impaired physical activity, and reduced quality of life. This study evaluated the efficacy and safety of risankizumab, a humanized immunoglobulin G1 monoclonal antibody that specifically inhibits interleukin 23 by binding to its p19 subunit, for the treatment of HS.
Baseline clinical, hormonal and molecular markers associated with clinical response to IL-23 antagonism in hidradenitis suppurativa: A prospective cohort study. [2023]Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL-23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.
Guselkumab, Risankizumab, and Tildrakizumab in the Management of Hidradenitis Suppurativa: A Review of Existing Trials and Real-Life Data. [2023]The treatment of hidradenitis suppurativa (HS) has always been a real challenge for dermatologists; to date, the only biologic drugs approved for HS are adalimumab, an anti-tumor necrosis factor (TNF)-α drug, authorized in 2015, and secukinumab, recently licensed. The management of this condition is challenging as the available treatments show variable results, and the course of the condition is often chronic-recurrent; therefore, it will be necessary for the future to identify new therapeutic targets for HS. In recent years, studies have focused on the development towards new therapeutic targets. The purpose of our review was to perform a comprehensive literature review of real-life data on anti-IL23 (guselkumab, tildrakizumab, and risankizumab) in HS to summarize the existing evidence on the efficacy and safety of these drugs. We selected 64 articles, among which 32 had the characteristics that we were looking for in our review. To date, the positive data expressed in real-life experiences contrast with the three existing Phase 2 studies conducted so far, where it seems that these drugs may be useful only for a subgroup of patients with HS whose features need to be elucidated. Data from Phase 3 studies and other real-life experiences, perhaps more detailed and with higher numbers, will certainly be needed to fully understand the efficacy and safety of this class of drugs.
Efficacy and safety of the oral Janus kinase 1 inhibitor povorcitinib (INCB054707) in patients with hidradenitis suppurativa in a phase 2, randomized, double-blind, dose-ranging, placebo-controlled study. [2023]Janus kinase 1 inhibition may alleviate hidradenitis suppurativa (HS)-associated inflammation and improve symptoms.
Alterations to the Hidradenitis Suppurativa Serum Proteome with Spleen Tyrosine Kinase Antagonism: Proteomic Results from a Phase 2 Clinical Trial. [2023]Hidradenitis Suppurativa (HS) is a disease in great need of novel therapies. Given the heterogeneous nature of the disease and the variable response to therapies, biomarkers are essential to predict response to therapies and increase our understanding of disease pathogenesis. Our recent Phase 2 clinical trial of Spleen Tyrosine Kinase antagonism using Fostamatinib in Hidradenitis Suppurativa demonstrated a 75% clinical response with the greatest benefit in individuals with elevated serum inflammation and Immunoglobulin G. We herein present results of an in-depth serum proteomic analysis in this patient cohort identifying downregulation of IL-12B, as well as B-cell associated proteins CCL19 and CCL20, and Interferon-gamma mediated proteins CXCL10 and CX3CL1. Clinical responders demonstrated greater reduction in serum IL-17A, IL-6, IL-8 and CX3CL1 compared to clinical non-responders. Baseline levels of CCL28 were associated with clinical response to fostamatinib therapy at week 12. Overall, this suggests that Fostamatinib, by targeting b cell receptor and Fc receptor activity in B cells, monocytes and macrophages has significant molecular impact on the inflammatory serum proteome of HS. Additional, potential therapeutic biomarkers may aid in patient selection for targeted therapy.