SBT777101 for Hidradenitis Suppurativa
(Regulate-HS Trial)
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Sonoma Biotherapeutics, Inc.
Must be taking: Systemic therapy, Biologic drug
Disqualifiers: Autoimmune disease, Complex HS, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This study will test the safety and effects of SBT777101 when given as a single dose to subjects with hidradenitis suppurativa. Increasing dose levels will be given after the safety at lower dose levels is shown.
Will I have to stop taking my current medications?
The trial requires that your medications for hidradenitis suppurativa be stable for at least 5 weeks before starting the study drug. This means you should not change your current medications during that time.
What data supports the effectiveness of the drug SBT777101 for treating Hidradenitis Suppurativa?
Research on similar treatments, like IL-17 inhibitors, shows promise in treating Hidradenitis Suppurativa, with drugs like brodalumab showing a 100% response rate in a small group of patients. This suggests that targeting similar pathways could be effective for SBT777101.
12345How does the drug SBT777101 differ from other treatments for hidradenitis suppurativa?
The drug SBT777101 is unique because it may target specific pathways involved in hidradenitis suppurativa, potentially offering a new approach compared to existing treatments like IL-17 inhibitors, which have shown effectiveness in some patients but not all. This could be particularly beneficial for patients who do not respond well to current therapies.
16789Eligibility Criteria
This trial is for individuals with Hidradenitis Suppurativa, a skin condition characterized by painful lumps under the skin. Participants must meet certain health criteria to join, but specific inclusion and exclusion details are not provided.Inclusion Criteria
Must agree to use highly effective method of contraception for at least 1 year post SBT777101 administration
Body mass index (BMI) must be ≤50 kg/m2
Total draining tunnel (dT) count must be ≤20
+4 more
Exclusion Criteria
I currently have an infection or often get infections.
I have a condition that weakens my immune system.
My condition is a severe form of hidradenitis suppurativa.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive a single ascending dose of SBT777101 to evaluate safety and effects
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after receiving the single dose
4 weeks
Participant Groups
The study is testing SBT777101, a new treatment given as a single dose to people with Hidradenitis Suppurativa. The trial will start at lower doses and increase only if those are shown to be safe.
3Treatment groups
Experimental Treatment
Group I: SBT777101 Dose Level 3Experimental Treatment1 Intervention
High dose SBT777101
Group II: SBT777101 Dose Level 2Experimental Treatment1 Intervention
Mid dose SBT777101
Group III: SBT777101 Dose Level 1Experimental Treatment1 Intervention
Low dose SBT777101
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
SLUCare Academic PavillionSaint Louis, MO
University of MinnesotaMinneapolis, MN
The University of Texas MD Anderson Cancer CenterHouston, TX
More Trial Locations
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Who Is Running the Clinical Trial?
Sonoma Biotherapeutics, Inc.Lead Sponsor
References
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.
Hidradenitis suppurativa: New insights into disease mechanisms and an evolving treatment landscape. [2023]Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic disabling and debilitating inflammatory disease with high unmet medical need. The prevalence of HS is 1-2% in most studies, although it is likely underreported and estimates vary globally due to variance in data collection methods, ethnicity, geographical location, and underdiagnosis. HS is characterized by persistent, painful cutaneous nodules, abscesses, and draining tunnels commonly affecting the axillary, anogenital, inguinal, and perianal/gluteal areas. Over time, chronic uncontrolled inflammation results in irreversible tissue destruction and scarring. Although the pathophysiology of HS has not been fully elucidated, the TNF-α and IL-17 pathways have an important role, involving multiple cytokines. Currently, treatment options include topical medications, systemic therapies including repeated and/or rotational courses of systemic antibiotics, retinoids, hormonal therapies, and various surgical procedures. The anti-TNF-α antibody adalimumab is currently the only biologic approved by both the Food and Drug Administration and the European Medicines Agency for HS; however, efficacy is varied, with clinical response reported in ∼50% of patients in Phase 3 trials. HS is a rapidly evolving field of discovery, with a diverse range of agents with distinct mechanisms of action currently being explored in clinical trials. Several other promising therapeutic targets have emerged recently, and agents targeting the IL-17 and JAK-STAT pathways are the most advanced in ongoing or completed Phase 3 clinical trials. Alongside limited therapeutic options, significant challenges remain in terms of diagnosis and disease management, with a need for better treatment outcomes. Other unmet needs include significant diagnostic delays, thus missing the therapeutic 'window of opportunity'; the lack of standardized outcome measures in clinical trials; and the lack of established, well-defined disease phenotypes and biomarkers.
A Systematic Review of Promising Therapeutic Targets in Hidradenitis Suppurativa: A Critical Evaluation of Mechanistic and Clinical Relevance. [2021]This systematic review identifies and critically evaluates the mechanistic and clinical evidence of new promising therapeutic targets in hidradenitis suppurativa (HS). Evidence for these targets is largely based on observational data with limited ex vivo and translational data from clinical trials. A number of placebo-controlled studies have been completed or are underway utilizing IL-1, IL-23, IL-17, complement, and Jak inhibition, although there is concern regarding elevated placebo response rates and the questionable validity of clinical scores in some participant subsets. Knowledge gaps are identified suggesting a direction for future mechanistic studies in HS, including more comprehensive inflammatory endotype profiling of disease.
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.
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.
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.
Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease. [2022]Hidradenitis Suppurativa (HS) is a chronic inflammatory skin disease of the pilosebaceous unit, clinically consisting of painful nodules, abscesses, and sinus tracts mostly in, but not limited to, intertriginous skin areas. HS can be defined as a complex skin disease with multifactorial etiologies, including-among others-genetic, immunologic, epigenetic, and environmental factors. Based on genetic heterogeneity and complexity, three different forms can be recognized and considered separately as sporadic, familial, and syndromic. To date, several genetic variants associated to disease susceptibility, disease-onset, and/or treatment response have been reported; some of these reside in genes encoding the gamma-secretase subunits whereas others involve autoinflammatory and/or keratinization genes. The aim of this perspective work is to provide an overview of the contribution of several genetic studies encompassing family linkage analyses, target candidate gene studies, and -omic studies in this field. In our viewpoint, we discuss the role of genetics in Hidradenitis suppurativa considering findings based on Sanger sequencing as well as the more recent Next Generation Sequencing (i.e., exome sequencing or RNA Sequencing) with the aim of better understanding the etio-pathogenesis of the disease as well as identifying novel therapeutic strategies.
Management of patients with hidradenitis suppurativa having underlying genetic variation: a systematic review and a call for precision medicine. [2023]Hidradenitis suppurativa (HS) is a chronic inflammatory condition of the pilosebaceous unit characterized by inflammation and hyperkeratinization. A small but significant proportion of patients with HS have a strong genetic susceptibility to (or a syndromic form of) the disease. Current HS treatment guidelines prioritize patients who manifest classic HS and may therefore not be suitable for the minority of patients harbouring genetically driven forms of disease. In this manuscript, we review the extant literature with regards to therapeutic strategies used for patients with HS having disease-associated genetic variants and syndromic forms of the condition. The findings of this review suggest that patients with HS harbouring underlying genetic variants may not be adequately represented in current European and British HS treatment guidelines. Moreover, these patients may be less responsive to the recommended therapeutic options. We therefore make recommendations for future therapeutic guidelines to incorporate considerations for the management of this patient subset.
The genetic aspects of hidradenitis suppurativa. [2023]Genetic aspects have a substantial role in hidradenitis suppurativa (HS) pathogenesis. A positive family history of HS occurs in about one-third of HS cases and is significantly higher in patients with early onset of the disease. Recent twin studies have shown a high heritability in HS, fortifying the importance of genetic factors in disease pathogenesis. Based on existing knowledge on the genomics of HS, the disease can be categorized as familial HS, sporadic, syndromic HS, and "HS plus" associated with other syndromes. In familial HS, autosomal dominant transmission is proposed, and monogenic inheritance is rare. This monogenic trait is related to mutations of γ-secretase component genes and Notch signaling or defects in inflammasome function. With newly discovered gene mutations, such as those related to innate and adaptive immunity, skin microbiome, inflammasome, epidermal homeostasis, and keratinization pathway, we can define HS as a polygenic, multifactorial, autoinflammatory disease. To fully elucidate the genetic aspects of HS, we need extensive, long-term global collaborations.