Lutikizumab for Hidradenitis Suppurativa (Intrepid Trial)
Palo Alto (17 mi)Age: Any Age
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AbbVie
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?Hidradenitis suppurativa (HS) is a chronic and often painful inflammatory skin disease which includes the forming of lumps, abscesses and scars in areas of the skin such as under the breasts, under armpits, inner thighs, groin and buttocks. This study will compare lutikizumab versus placebo for the treatment of adult and adolescent participants with moderate to severe HS .
Lutikizumab is an investigational drug being developed for the treatment of HS. During Period 1 of the study, participants will placed in 1 of 2 groups called treatment arms. There is a 1 in 2 chance that participants will be assigned to placebo. Around 1280 adult and adolescent participants with moderate to severe HS will be enrolled in the study at approximately 275 sites world wide. During Period 2, participants that were part of the lutikizumab treatment arm in Period 1 will be re-randomized to 1 of 2 lutikizumab treatment arms. Participants that were part of the Placebo arm in Period 1 will start Period 2 with an initiation of lutikizumab followed by a re-randomization to 1 of 2 lutikizumab treatment arms.
In Period 1, participants will receive subcutaneous injections of lutikizumab or placebo every week for 16 weeks. In Period 2, participants that were randomized to lutikizumab in Period 1 will receive subcutaneous injections of lutikizumab every week or every other week for 36-weeks. Participants that were randomized to the placebo arm in Period 1 will receive subcutaneous injections of lutikizumab every week for 16 weeks, then either every week or every other week for 20 weeks
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires and diaries.
Is the drug Lutikizumab a promising treatment for Hidradenitis Suppurativa?The information provided does not mention Lutikizumab as a promising treatment for Hidradenitis Suppurativa. It focuses on other drugs like adalimumab, risankizumab, and others that target specific molecules involved in the disease.1481112
What safety data exists for Lutikizumab in treating Hidradenitis Suppurativa?The provided research does not contain specific safety data for Lutikizumab in treating Hidradenitis Suppurativa. The studies focus on the safety and efficacy of adalimumab and its biosimilars for this condition. Therefore, no direct safety data for Lutikizumab is available in the given research.2671013
What data supports the idea that Lutikizumab for Hidradenitis Suppurativa is an effective drug?The available research does not provide specific data on the effectiveness of Lutikizumab for Hidradenitis Suppurativa. However, it mentions other treatments like IL-17 inhibitors and IL-23 antagonists, which have shown positive results. For example, IL-17 inhibitors had about two-thirds of patients responding positively, and IL-23 antagonism with risankizumab showed a 69.2% response rate. These findings suggest that targeting similar pathways might be effective, but there is no direct evidence for Lutikizumab itself.3591214
Do I have to stop taking my current medications for this trial?The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
Eligibility Criteria
This trial is for adults and adolescents with moderate to severe Hidradenitis Suppurativa (HS), a painful skin condition. Participants must have been diagnosed at least 6 months ago, have five or more abscesses or nodules, and HS lesions in two areas of the body, one being at least Hurley Stage II.Inclusion Criteria
My HS condition is at least at a moderate severity stage.
I have HS lesions in two or more separate areas.
Treatment Details
The study tests Lutikizumab against a placebo in treating HS. Initially, participants are randomly assigned to receive either Lutikizumab or placebo injections weekly for 16 weeks. Afterwards, they may continue with different dosing schedules of Lutikizumab for up to 36 weeks.
6Treatment groups
Experimental Treatment
Group I: Period 2: Placebo to Lutikizumab Group Every WeekExperimental Treatment1 Intervention
Participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every week through Week 52
Group II: Period 2: Placebo to Lutikizumab Group Every Other WeekExperimental Treatment2 Interventions
The participants that were assigned Placebo in Period 1 and initiated lutikizumab in Period 2 will then be re-randomized to lutikizumab Dose A every other week through Week 52
Group III: Period 2: Placebo to Lutikizumab GroupExperimental Treatment1 Intervention
Participants randomized to Placebo in Period 1 who complete Week 16 of the study will initiate lutikizumab with Dose B followed by Dose A every week.
Group IV: Period 2: Lutikizumab Every WeekExperimental Treatment1 Intervention
Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A through Week 52
Group V: Period 2: Lutikizumab Every Other WeekExperimental Treatment2 Interventions
Participants randomized to lutikizumab in Period 1 who complete Week 16 of the study will be re-randomized to lutikizumab Dose A every other week though week 52
Group VI: Period 1Experimental Treatment2 Interventions
Participants will be randomized to either Lutikizumab Dose B at baseline followed by Lutikizumab Dose A, or a matching placebo dose equivalent for both, every week through Week 16 .
Find a clinic near you
Research locations nearbySelect from list below to view details:
Texas Dermatology Research Center /ID# 264488Plano, TX
Ziaderm Research LLC /ID# 263511Miami, FL
Clinical Trials Research Institute /ID# 263743Thousand Oaks, CA
Arlington Dermatology /ID# 263410Rolling Meadows, IL
More Trial Locations
Loading ...
Who is running the clinical trial?
AbbVieLead Sponsor
References
Successful Treatment of Recalcitrant Hidradenitis Suppurativa with Adalimumab. [2021]Hidradenitis suppurativa is a chronic disease that affects the apocrine gland-bearing regions of the body. The etiology of this disorder is poorly understood, but most likely is a complex process involving follicular apocrine occlusion with subsequent perifolliculitis. Many treatment options have been reported with varying degrees of success, including topical and oral therapy and surgical procedures. Recently, TNF-alpha antagonists have been reported as effective therapy in a few patients. We report here a patient who initially responded to infliximab but developed an infusion reaction to this medication. After subsequent treatment with adalimumab, the patient's disease improved dramatically and has been maintained under excellent control for over 15 months. We propose that TNF-alpha inhibitors, particularly monoclonal antibody based agents, are a viable treatment option in patients with severe, recalcitrant HS and that a patient may be safely and successfully treated with the fully human monoclonal antibody adalimumab in cases in which the chimeric monoclonal antibody infliximab therapy is not tolerated.
A prospective open-label clinical trial of adalimumab for the treatment of hidradenitis suppurativa. [2015]To evaluate the safety and efficacy of adalimumab for the management of hidradenitis suppurativa (HS).
Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. [2018]Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS).
Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa. [2018]Hidradenitis suppurativa (HS) is a serious, debilitating, chronic inflammatory skin disease. Adalimumab is a fully human, immunoglobulin G1 monoclonal antibody specific for tumor necrosis factor-alpha recently approved for use in patients with HS. The aim of this study is to describe the population pharmacokinetics and immunogenicity of adalimumab in adult patients with HS.
Medical management of hidradenitis suppurativa. [2018]Hidradenitis suppurativa is a chronic inflammatory disease of the folliculo-infundibular unit for which no individual treatment is uniformly effective. A wide array of therapies has been reported successful in the treatment of hidradenitis, although few high-quality clinical trials have been conducted. Comparing the effectiveness of different therapies has proven challenging due to heterogeneity and limited validation of outcome measures. We performed a systematic review of clinical trials of medical treatments for hidradenitis, yielding 8 articles reporting on 9 trials of antibiotic, hormonal, and biologic therapies. In addition, we discuss existing observational data on commonly used therapeutic regimens, as well as the outcome measures driving clinical research in hidradenitis suppurativa.
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.
Overview and update on biologic therapy for moderate-to-severe hidradenitis suppurativa. [2019]Hidradenitis suppurativa (HS) is a frequently devastating inflammatory skin disorder. Although many treatments have been tried and tested to date, there is only one Food and Drug Administration-approved treatment option, adalimumab, which is currently indicated for moderateto- severe HS. Our understanding of the management of HS with biologic agents and with nonantibiotic and/ or antimicrobial systemic therapies continues to evolve. In this article, we summarize the existing data on biologics and other small-molecule systemic agents, as well as share our personal experiences with the pharmacological management of HS in the clinical setting. Continued challenges that limit our ability to study and treat this disease effectively include a lack of a universally employed scoring system for disease severity, high variability in clinical presentation, high cost of off-label therapy, and the scarcity of long-term studies on treatment response and medication safety.
Target molecules for future hidradenitis suppurativa treatment. [2022]The registration of the tumour necrosis factor-α inhibitor adalimumab in 2015 was a major step forward in the treatment of hidradenitis suppurativa/acne inversa (HS). However, it soon became evident that the effectiveness of adalimumab in daily practice was highly variable. A significant unmet medical need of HS patients remained, and the search for novel therapeutic targets was intensified. During the 10th European Hidradenitis Suppurativa Foundation (EHSF) e.V. Conference, reknown international HS investigators virtually presented and discussed the published data on these potential target molecules for future HS treatment. This article addresses the most promising molecules currently under investigation from a pathophysiological and clinical point of view. With phase III trials ongoing, the anti- interleukin (IL)-17 biologics bimekizumab and secukinumab are in the most advanced stage of clinical development showing promising results. In addition, targeting IL-1α with bermekimab has shown encouraging results in two clinical trials. Directing treatment at neutrophil recruitment and activation by targeting IL-36 with spesolimab fits well in the pathogenic concept of HS and clinical phase II trial results are pending. In contrast to in situ evidence, Complement 5a (C5a) and C5a receptor blockade have only shown greater clinical benefit in patients with severe HS. Inhibition of Janus kinase (JAK) 1 signalling in HS showed clinical efficacy only in the highest dosage, highlighting that careful surveillance of the balance between safety and efficacy of JAK inhibition is warranted. Overall, clinical efficacies of all novel treatments reported so far are modest. To guide drug development, more and better-defined translational data on the pathogenesis of this severe and enigmatic inflammatory skin disease are required.
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.
Switching from Adalimumab Originator to Biosimilar in Patients with Hidradenitis Suppurativa Results in Losses of Response-Data from the German HS Registry HSBest. [2022]Since 2021, adalimumab biosimilar ABP 501 can be used alternatively to adalimumab originator (ADAO) in the treatment of hidradenitis suppurativa (HS). Effectiveness and safety data remain scarce. We investigated the impact of switching from ADAO to ABP 501 on disease severity and the occurrence of adverse events (AEs) in patients with HS. We analyzed clinical data on patients enrolled in the German HSBest registry. Evaluation outcomes were assessed at three time points (baseline of originator (t0), prior to switching to biosimilar (t1) and 12 to 14 weeks after switching (t2)) and included patient-reported AEs and disease severity using the International Hidradenitis Suppurativa Severity Score System (IHS4) score. In total, 94 patients were switched from ADAO to ABP 501. Overall, 33.3% (n = 31/94) of the patients developed AEs and/or loss of response (LoR) within 12 to 14 weeks after switching. Of these, 61.3% (n = 19/31) experienced LoR but no AEs, 22.6% (n = 7/31) LoR combined with AEs and 16.1% (n = 5/31) AEs only. Our study showed that switching HS patients from ADAO to ABP 501 does significantly affect treatment effectiveness. Switching patients who are on remission maintenance therapy should be viewed critically.
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.
Real-world safety and effectiveness of adalimumab in patients with hidradenitis suppurativa: A 52-week analysis of a postmarketing surveillance study in Japan. [2023]Adalimumab is a human monoclonal antibody against tumor necrosis factor-α that was approved in Japan for the treatment of hidradenitis suppurativa (HS), a chronic recurrent inflammatory skin disease. We report the results of the final analysis of the postmarketing surveillance (PMS) study (ClinicalTrials.gov: NCT03894956), which evaluated the 52-week safety and efficacy of adalimumab for HS treatment in real-world clinical practice in Japan. This multicenter, prospective, open-label, observational study (March 2019 to May 2021) included patients with HS treated with subcutaneous adalimumab at doses following the package insert. The primary endpoint was safety, and the secondary endpoints were effectiveness, including HS clinical response (HiSCR), C-reactive protein (CRP), skin pain, and Dermatology Life Quality Index (DLQI). Of the 84 patients registered at 65 sites, 83 patients were included in the analyses. Adverse drug reactions (ADRs) were reported by 10 (12.0%) patients; two patients reported a serious ADR, including one patient with serious infection. Other safety events of special interest reported were liver disorder and dermatitis psoriasiform (one patient each). Almost all patients with ADRs were recovering or had recovered, except for one patient who experienced a serious ADR of liver disorder and died. At 12 weeks, 55.4% of patients achieved HiSCR; this increased to 60.5% and 62.8% at 24 and 52 weeks of adalimumab treatment, respectively. Significant reductions from baseline in CRP (P
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.