Sonelokimab for Hidradenitis Suppurativa
Recruiting in Palo Alto (17 mi)
+86 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: MoonLake Immunotherapeutics AG
Disqualifiers: Active skin disease, Autoimmune disease, IBD, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?This is a study to evaluate the clinical efficacy and safety of sonelokimab administered subcutaneously compared with placebo in the treatment of adult participants with moderate to severe hidradenitis suppurativa. Participants will be randomized 2:1 to either sonelokimab or matching placebo up to Week 16.
Do I have to stop taking my current medications for the trial?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.
What data supports the effectiveness of the drug Sonelokimab for treating Hidradenitis Suppurativa?
Research shows that drugs targeting the IL-17 pathway, like secukinumab, have been effective in treating Hidradenitis Suppurativa (HS), with a significant number of patients responding positively. Since Sonelokimab also targets IL-17, it may offer similar benefits for HS patients.
12345What safety data exists for Sonelokimab and similar treatments for Hidradenitis Suppurativa?
Most biologic treatments for Hidradenitis Suppurativa, including those targeting the IL-17 pathway, are generally well tolerated with infections being the most common side effect. While specific safety data for Sonelokimab is not detailed, similar treatments have shown a good safety profile in clinical trials.
12678What makes the drug Sonelokimab unique for treating Hidradenitis Suppurativa?
Sonelokimab is unique because it is a nanobody, which is a small, single-domain antibody that can specifically target and block certain proteins involved in inflammation, potentially offering a more precise and effective treatment for Hidradenitis Suppurativa compared to traditional therapies.
910111213Eligibility Criteria
Adults with moderate to severe hidradenitis suppurativa, having at least 5 inflammatory nodules and lesions in 2 or more areas, one with fistulas. They must have had symptoms for over 6 months and not responded well to antibiotics.Inclusion Criteria
My skin condition didn't improve after antibiotic treatment.
I am at least 18 years old.
I have HS with sores in 2 or more areas, including at least one with fistulas.
+2 more
Exclusion Criteria
Participants with known hypersensitivity to sonelokimab or any of its excipients
I do not have any autoimmune diseases that could affect my HS symptom assessment.
I do not have any skin conditions that could affect HS assessment.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive sonelokimab or placebo subcutaneously, with dosing adjustments from Weeks 0 to 48
48 weeks
Bi-weekly visits initially, then monthly
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing the effectiveness of Sonelokimab given under the skin versus a placebo in treating hidradenitis suppurativa. Participants will be randomly assigned to receive either Sonelokimab or placebo until Week 16.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: sonelokimabExperimental Treatment1 Intervention
Subjects randomized to this arm will receive sonelokimab 120 mg Q2W from Weeks 0 to 6 then 120 mg Q4W starting at Week 8 up to Week 48.
Group II: PlaceboPlacebo Group1 Intervention
Subjects randomized to this arm will receive placebo Q2W from Weeks 0 to 6 then Q4W starting at Week 8 up to Week 16. They will receive sonelokimab 120 mg Q2W for 4 doses from Weeks 16 to 22 then Q4W from Week 24 up to Week 48
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Clinical SiteAventura, FL
Clinical SiteHialeah, FL
Clinical SiteAnn Arbor, MI
Clinical SiteLas Vegas, NV
More Trial Locations
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Who Is Running the Clinical Trial?
MoonLake Immunotherapeutics AGLead Sponsor
References
Severe hidradenitis suppurativa responding to treatment with secukinumab: a case report. [2022]An inappropriate immunological response to an unknown antigen has been suggested to play a role in the pathogenesis of hidradenitis suppurativa (HS). Studies have identified elevated levels of several proinflammatory cytokines, including interleukin (IL)-17A and tumour necrosis factor-α, nominating these as possible therapeutic targets.1 Secukinumab is an IL-17A monoclonal antibody, which binds to IL-17A and inhibits the cytokine interaction with the IL-17 receptors, inhibiting the inflammatory cascade. Here we report a case of a 47-year-old man, with Hurley stage III lesions on the neck, axillae, breasts, genital skin and buttocks, who had experienced only temporary benefit from different medical treatments over several years. After 12 weeks of treatment with secukinumab, the number of lesions reported by the patient within the period of the last 4 weeks was reduced from 23 to seven, his pain visual analogue scale (VAS) score was reduced from 5 to 3 and pain/utility/handicap VAS score was reduced from 7 to 4. These results may be taken to imply that IL-17 blockade could provide a possible therapeutic approach in the treatment of HS.
Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review. [2022]The IL-17 pathway is a potential therapeutic target shown to be implicated in hidradenitis suppurativa (HS), however, it remains unclear whether evidence from mechanistic studies may translate into clinical practice. This systematic review summarizes available treatment outcomes of IL-17 inhibitors in patients with HS. Embase, MEDLINE, PubMed, and clinicaltrials.gov were comprehensively searched on February 26, 2021 to include 16 original studies representing 128 patients with HS (mean age: 36.5 years; age range: 21-47 years; male: 50.0%). Treatment outcomes were reported for the following biologics: secukinumab (n = 105), brodalumab (n = 22), and ixekizumab (n = 1). Patients were classified as responders or non-responders according to achievement of a positive response/improvement based on criteria established for each included study. For secukinumab 57.1% (n = 60/105) of patients were responders in a mean response period of 16.2 weeks and 42.9% (n = 45/105) were non-responders; for brodalumab, 100.0% (n = 22/22) of patients were responders within 4.4 weeks; and the one patient treated with ixekizumab was a responder within 10 weeks. In conclusion, IL-17 inhibitors may serve as an effective therapeutic target in approximately two-thirds of patients with HS and can be considered in those who are refractory to other treatment modalities. We also stress the importance of consistent outcome measures to enhance evidence synthesis, decrease reporting bias, provide potential for future meta-analysis, and ultimately improve clinical outcomes for patients with HS.
IL-17 Inhibition: A Valid Therapeutic Strategy in the Management of Hidradenitis Suppurativa. [2023]Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a significant negative impact on the quality of life of patients. To date, the therapeutic landscape for the management of the disease has been extremely limited, resulting in a profound unmet need. Indeed, adalimumab, an anti-tumor necrosis factor (TNF)-α monoclonal antibody, is the only approved biologic agent for HS, obtaining a therapeutic response in only 50% of HS patients. Numerous clinical trials are currently ongoing to test novel therapeutic targets in HS. The IL-17-mediated cascade is the target of several biologic agents that have shown efficacy and safety in treating moderate-to-severe HS. Both bimekizumab and secukinumab, targeting IL-17 in different manners, have successfully completed phase III trials with promising results; the latter has recently been approved by EMA for the treatment of HS. The aim of this review is to summarize the current state of knowledge concerning the relevant role of IL-17 in HS pathogenesis, highlighting the key clinical evidence of anti-IL-17 agents in the treatment of this disease.
Hidradenitis Suppurativa Is Characterized by Dysregulation of the Th17:Treg Cell Axis, Which Is Corrected by Anti-TNF Therapy. [2018]Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating disease of hair follicles with 1-4% prevalence and high morbidity. There is a dearth of information on the pathogenesis and immune dysregulation underlying HS; therefore, we carried out a detailed analysis of skin-infiltrating T cells. Cells isolated from skin biopsy samples and blood from HS patients and healthy control subjects were analyzed by 16-parameter flow cytometry to provide detailed profiles of CD4 T-cell subsets. We observed substantial infiltration of inflammatory T cells with a striking T helper (Th) type 17-skewed cytokine profile in HS skin; these cells expressed the Th17 lineage marker CD161 and IL-17, as well as proinflammatory cytokines GM-CSF, IL-22, IFN-γ, and tumor necrosis factor. Regulatory T cells were also enriched in HS lesional skin; however, the ratio of Th17 to regulatory T cells was nonetheless highly dysregulated in favor of Th17 cells. In contrast, lesional skin from anti-tumor necrosis factor-treated HS patients who showed substantial clinical improvement exhibited a significant reduction in the frequency of Th17 cells and normalization of the Th17 to regulatory T cell ratio. These data suggest that inhibition of pathogenic IL-17 via tumor necrosis factor blockade is associated with improvement in immune dysregulation in HS and may provide a rationale for targeting IL-17 in the disease.
Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa. [2023]Skin disorders affect ∼40% of the human population. One of the most debilitating cutaneous disorders is Hidradenitis suppurativa (HS), a noncommunicable chronic inflammatory disease with an estimated global prevalence of 0.4% to 2.5%. In January 2011, high levels of IL-17 were discovered in skin lesions of HS patients. In the following years, translational and clinical research led to a better understanding of the pathogenesis of HS. In June 2023, more than 12 years after the initial note, secukinumab, an anti-IL-17A monoclonal antibody, was approved for the treatment of moderate to severe HS. This is the next milestone in improving the treatment of these patients after the approval of the anti-TNF-α monoclonal antibody adalimumab in 2015. In this review article, we present the IL-17 pathway in HS and discuss the use of secukinumab as a therapeutic option for this disease. Our review starts with a description of the epidemiology, clinical features, etiology, and pathogenesis of HS. An overview of the IL-17/IL-17 receptor system in general and a detailed description of the known facts about the expression and action of IL-17 in HS follow. Afterward, we consider the results of clinical trials evaluating the safety and efficacy of IL-17 inhibitors in HS. Finally, a comparison is made between secukinumab and adalimumab and the characteristics of the patients that may be particularly suitable for each of these biologics are described.
Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. [2018]Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS).
Defining targets to defeat hidradenitis suppurativa. [2019]Immunological data implicates IL-17 pathway in the pathogenesis of hidradenitis suppurativa.
Systematic review of immunomodulatory therapies for hidradenitis suppurativa. [2020]Background: Greater understanding of the roles of tumor necrosis factor-α, IL-1β, IL-10, and the IL-23/T-helper (Th) 17 and IL-12/Th1 pathways in immune dysregulation in moderate/severe hidradenitis suppurativa (HS) has helped in developing new regimens. We aim to review the use of different immunomodulatory therapies used to manage HS. Methods: A comprehensive literature search was conducted on the PubMed and Clinicaltrials.gov databases from 1 January 1947 to 31 December 2018. Only clinical trials, case reports, case series and retrospective analyses published in the English language were included. Results: Our search yielded 107 articles and 35 clinical trials, of which 15 are still ongoing. The tumor necrosis factor-α inhibitors adalimumab and infliximab were the most comprehensively studied agents. Published data from clinical trials support the efficacy of adalimumab, infliximab, anakinra, ustekinumab, bermekimab and apremilast but not etanercept and MEDI8968. Clinical trials for CJM112 have been completed, with results awaiting publication. Trials are underway for secukinumab, IFX-1, INCB054707 and bimekizumab. Biologics used in smaller cohorts include canakinumab, golimumab and rituximab. Most agents are well tolerated and demonstrate a good safety profile, with the most commonly reported adverse event being infections. Discussion and conclusions: To date, adalimumab is the only biologic which has been approved by the United States Food and Drug Administration for HS. However, other agents also show promise, with further trials underway to evaluate their efficacy, tolerability and safety profiles. Different clinical measurement scores and endpoints used to make direct comparison difficult. Longitudinal surveillance and pooled registry data are paramount to evaluate the long-term safety profile and efficacy of therapy.
Nanobodies targeting the interaction interface of programmed death receptor 1 (PD-1)/PD-1 ligand 1 (PD-1/PD-L1). [2023]Targeting the interaction interface is an effective strategy to obtain programmed death receptor 1 (PD-1)/PD-1 ligand 1 (PD-L1) nanobody blockers. To validate this strategy, the interaction interface between PD-1 and the PD-L1 extracellular domain were analyzed using Cn3D 4.1. The peptide PD-1125-136 located at the interface of PD-1 was selected as the antigen to screen nanobodies from a humanized nanobody phage display library. Six different nanobodies were screened, with molecular weights of 12 ∼ 13 kDa, excluding a single basic protein. The nanobody with the longest CDR3 region, termed PD-1-Nb-B20, was selected for further analysis. For mass production, the C-terminal His6-tagged nanobody coding sequence was optimized and cloned into pET-21b for over-expression under the T7 promoter in Escherichia coli BL21 (DE3). PD-1-Nb-B20 was expressed and pancreatic adenocarcinoma cells BxPC-3 over-expressing PD-L1 were selected for nanobody competitive inhibition assays. The purified nanobodies significantly inhibited PD-1 binding to the surface of target cells, indicating their ability to block the PD-1/PD-L1 interaction.
Evaluation the potential of recombinant anti-CD3 nanobody on immunomodulatory function. [2020]T cells are the most predominant effector cells in immune-mediated elimination of cancer and circumventing tumor progression. Among various approaches, T cells activation by specific antibodies independently of their TCR specificity, is considered as an effective approach to circumvent tumor progression. The most common surface marker for all T cells which is crucial for T cell activation is regarded as CD3. Therefore, the goal of our study was to evaluate the preclinical efficacy of recombinant anti-CD3 nanobody. To this end, anti-CD3 sequence, was PCR amplified, following cloning and expression in E.coli and purification, the purified nanobody with a molecular weight of ∼17 kDa was confirmed by western blot. Furthermore, flow cytometry analysis demonstrated that purified nanobody could bind to CD3 on Jurkat cell line. Subsequently, results from inoculation of 3 μg/g of nanobody to tumor bearing balb/c mice indicate inhibition of tumor growth. Furthermore, circulating levels of tumoricidal cytokines such as IL-2 and IFNγ were raised whereas tolerogenic cytokines such as IL-4, 6 and 10 were decreased at the end of the treatment. Moreover, IHC analysis confirmed the presence and also the percentage of TILs in tumor sites in response to anti-CD3 therapy. Hence, our results suggest that the purified anti-CD3 nanobody may become a promising candidate for targeting and activating CTLs to induce anti-tumor responses and may provide groundwork for future studies involving other kind of cancers.
G250 Antigen-Targeting Drug-Loaded Nanobubbles Combined with Ultrasound Targeted Nanobubble Destruction: A Potential Novel Treatment for Renal Cell Carcinoma. [2022]We intended to design G250 antigen-targeting temsirolimus-loaded nanobubbles (G250-TNBs) based on the targeted drug delivery system and to combine G250-TNBs with ultrasound targeted nanobubble destruction (UTND) to achieve a synergistic treatment for renal cell carcinoma (RCC).
In vivo tumor-suppressing and anti-angiogenic activities of a recombinant anti-CD3ε nanobody in breast cancer mice model. [2020]Aim: Achievements in cancer immunotherapy require augmentation of a host's anti-tumor immune response for anti-cancer modality. Materials & methods: Different concentrations of recombinant anti-CD3 nanobody were administered at predetermined time intervals during a 24-day treatment period and then expression of angiogenic biomarkers including VEGFR2, MMP9 and CD31, as well as tumor cell proliferation marker ki67, was determined in tumor sections by immunohistochemistry. Furthermore, expression of cytokines was examined in peripheral blood of mice. Results: Based on our results, administration of nanobody could reduce biomarker expression in tumor sections. Tumor growth was also delayed and survival rate was increased in response to nanobody treatment. Moreover, expression of pro-inflammatory cytokines was reduced. Conclusion: In conclusion, we demonstrated that administration of nanobody could effectively suppress angiogenesis as well as tumor growth.
[Single-Domain Antibodies Used to Pretreat the Human Urinary Proteome in Cancer Biomarker Testing]. [2022]A number of single-domain antibodies (nanobodies) obtained previously to major marker blood proteins were tested as tools to preprocess urine samples from patients with bladder cancer. Nanobody-based tools demonstrated unique possibilities for noninvasive diagnostic studies along with other conventional methods, such as electrophoresis and, in prospect, mass spectrometric analysis. A testing of 22 samples from bladder cancer patients showed that the development of bladder cancer is accompanied by an increase in the urine contents of major blood proteins, including those known as potential bladder cancer biomarkers. New nanobody-based immunosorbents allow both specific enrichment and specific removal of particular antigenic proteins and subproteomes associated with them from a biological fluid. The isolation of immune complexes from the urine of a particular patient is of particular interest. An initial study of the complexes showed not only increased contents of IgA and IgG at advanced stages of the disease, but also many other components, which provide potential biomarkers of the pathological process in a particular patient. It is intended to use the approaches proposed in this work in a future larger-scale study of urine samples from patients with bladder cancer at different stages of the disease in order to identify new promising biomarkers of bladder cancer.