Topical Ruxolitinib Cream for Hidradenitis Suppurativa
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Milton S. Hershey Medical Center
Must not be taking: JAK inhibitors, Systemic corticosteroids
Disqualifiers: Active skin disease, Pregnancy, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?Investigators hypothesize that ruxolitinib 1.5% cream is an effective therapy for HS participants through inhibition of inflammatory activity.
Investigators aim to:
* Demonstrate the clinical efficacy of ruxolitinib 1.5% cream in decreasing the clinical disease activity after 16 weeks of treatment.
* Investigate the impact of ruxolitinib 1.5% cream on skin inflammation through translational analyses of skin biopsy samples.
Will I have to stop taking my current medications?
You may need to stop some medications, but others can be continued if they have been at a stable dose for a certain period. For example, biologic medications can be continued if stable for 6 months, oral antibiotics for 28 days, hormone-based therapy for 4 months, and oral retinoids for 90 days. However, other topical therapies must be stopped 14 days before the study starts.
What data supports the effectiveness of the drug Ruxolitinib 1.5% Cream for treating hidradenitis suppurativa?
Ruxolitinib cream has shown effectiveness in treating atopic dermatitis, a skin condition, by reducing itchiness and improving skin condition. While it hasn't been specifically studied for hidradenitis suppurativa, its success in treating similar inflammatory skin conditions suggests it might be beneficial.
12345Is topical Ruxolitinib cream safe for use in humans?
Topical Ruxolitinib cream has been well tolerated in studies for conditions like atopic dermatitis, with a safety profile similar to a placebo cream and only infrequent mild skin reactions like stinging or burning. It has minimal absorption into the body, which supports its safety compared to oral forms of the medication.
23567How is Ruxolitinib cream different from other drugs for hidradenitis suppurativa?
Ruxolitinib cream is unique because it is a topical treatment, meaning it is applied directly to the skin, unlike other drugs for hidradenitis suppurativa that are usually injected or taken orally. This cream works by targeting specific pathways involved in inflammation, potentially offering a new approach for managing this condition.
1891011Eligibility Criteria
This trial is for individuals aged 12 or older with Hidradenitis Suppurativa (HS), specifically Hurley Stage I or II. Participants must have active HS lesions in at least one area, a minimum of 3 inflammatory lesions, and a diagnosis of HS for at least 3 months. They should not have other skin conditions that could affect the study, be pregnant or lactating, and must agree to use contraception during the study.Inclusion Criteria
My current medications have been stable and won't change during the study.
I had surgery in the treatment area more than 3 months ago.
I have Hidradenitis suppurativa at an early or moderate stage.
+6 more
Exclusion Criteria
Does not have reliable internet access for weekly electronic surveys
I do not have any active skin conditions that could affect HS assessment.
Pregnant (or considering becoming pregnant) or lactating females
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
8 weeks
Treatment
Participants receive topical Ruxolitinib 1.5% cream, twice daily for 16 weeks
16 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial tests Ruxolitinib 1.5% cream's effectiveness on HS by reducing inflammation over a period of 16 weeks. It also examines how this topical treatment affects skin inflammation through analysis of biopsy samples from participants.
1Treatment groups
Experimental Treatment
Group I: Open-labelExperimental Treatment1 Intervention
Topical Ruxolitinib 1.5% Cream, twice daily for 16 weeks
Ruxolitinib 1.5% Cream is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Opzelura for:
- Atopic dermatitis
- Nonsegmental vitiligo
🇪🇺 Approved in European Union as Opzelura for:
- Atopic dermatitis
- Nonsegmental vitiligo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Penn State Hershey Medical CenterHershey, PA
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Who Is Running the Clinical Trial?
Milton S. Hershey Medical CenterLead Sponsor
Incyte CorporationIndustry Sponsor
References
Secukinumab in the treatment of hidradenitis suppurativa. [2023]The IL-17 pathways are involved in the pathophysiology of many inflammatory skin conditions, including hidradenitis suppurativa. Secukinumab, an IL-17A inhibitor, has been used for years in inflammatory skin disorders such as psoriasis. To date, the only US FDA-approved medication for hidradenitis suppurativa is adalimumab, a TNF-α inhibitor. Recently, secukinumab has demonstrated promising results in the treatment of hidradenitis suppurativa in the phase III SUNSHINE and SUNRISE clinical trials. This article reviews the mechanism of action of secukinumab and summarizes the available clinical efficacy and safety data regarding secukinumab in the management of hidradenitis suppurativa.
Ruxolitinib Cream 1.5%: A Review in Mild to Moderate Atopic Dermatitis. [2023]Ruxolitinib cream 1.5% (OPZELURA™) is a topical formulation of ruxolitinib, a potent, selective inhibitor of Janus kinase (JAK)1 and JAK2. The targeting of these kinases is associated with therapeutic benefits in patients with atopic dermatitis (AD). In two identically designed, multinational, phase III studies in patients aged ≥ 12 years with mild to moderate AD, ruxolitinib cream 1.5% improved measures of disease severity, pruritus and sleep disturbance relative to vehicle cream when applied twice daily for 8 weeks. Disease severity was controlled for the next 44 weeks when applied as needed to active lesions. Ruxolitinib cream 1.5% was well tolerated in this patient population; its safety profile was similar to that of vehicle cream over the short term, with the types of treatment-emergent adverse events typical of those seen in the vehicle-controlled period over the longer term. Moreover, application site treatment-emergent adverse events indicative of skin tolerability issues (e.g. stinging/burning sensation) were infrequent and no safety findings suggestive of systemic JAK inhibition were identified. Although further longer-term data would be of use, ruxolitinib cream 1.5% provides an alternative to established topical agents (e.g. corticosteroids and calcineurin inhibitors) for the treatment of mild to moderate AD in adults and adolescents.
A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. [2022]Ruxolitinib cream is a topical formulation of ruxolitinib, an inhibitor of Janus kinase 1 and Janus kinase 2.
Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. [2023]Ruxolitinib cream is a topical formulation of ruxolitinib, a Janus kinase (JAK) 1/JAK2 inhibitor.
Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy. [2023]Ruxolitinib cream is a topical formulation of ruxolitinib, a selective inhibitor of Janus kinase (JAK) 1 and JAK2. In two phase 3 studies in adults and adolescents (aged ≥12 years) with atopic dermatitis (AD; TRuE-AD1/TRuE-AD2), significantly more patients who applied ruxolitinib cream versus vehicle cream achieved Investigator's Global Assessment treatment success (IGA-TS; IGA score of 0/1 with ≥2-point improvement from baseline) at week 8 (primary endpoint). This post hoc analysis evaluated the efficacy, safety, and disease control of ruxolitinib cream in patients with AD who did not achieve IGA-TS at week 8. Patients in TRuE-AD1/TRuE-AD2 (N = 1249) were randomized 2:2:1 to apply twice-daily 0.75% ruxolitinib cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks followed by a long-term safety period in which patients applied ruxolitinib cream as needed. In this pooled analysis, clinically meaningful response thresholds included ≥50% improvement in the Eczema Area and Severity Index, ≥2-point reduction in the Itch Numerical Rating Scale, ≥4-point improvement in the Dermatology Life Quality Index (DLQI) or ≥6-point improvement in Children's DLQI, and ≥1-point reduction in IGA from baseline. Among patients who did not achieve IGA-TS at week 8 (n = 584), significantly more patients who applied either strength ruxolitinib cream versus vehicle achieved each response threshold at week 8. A response in ≥1 clinically meaningful endpoint was achieved in significantly more patients who applied ruxolitinib cream (93.4%/90.9% for 0.75%/1.5% ruxolitinib cream, respectively) versus vehicle (69.0%, both P
Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. [2021]Ruxolitinib is a selective and potent inhibitor of Janus kinase (JAK) 1 and JAK2. It is approved for the treatment of patients with intermediate or high-risk myelofibrosis, or those with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. To investigate its carcinogenic potential, ruxolitinib was administered by oral gavage once daily to Tg.rasH2 mice for 6 months at doses of 15, 45 or 125 mg/kg/day, and to Sprague-Dawley (Crl:CD) rats for 2 years at 10, 20 or 60 mg/kg/day. Ruxolitinib had no effect on survival, and did not increase the incidence of any neoplastic findings in either species. Exposure (AUC) was similar to or exceeded that associated with therapeutic use. Lymphoid depletion and a decrease in extramedullary hematopoiesis in the spleen occurred in rats, which were attributed to the pharmacologic activity of ruxolitinib. In Tg.rasH2 mice, increased inflammation in the nasal cavity was observed. Dose-dependent decreases in a number of spontaneous neoplastic/preneoplastic lesions were observed in rats, including mammary tumors in females, adrenal pheochromocytomas in males, hepatocellular adenomas/carcinomas in males, and hepatic basophilic (males and females) and eosinophilic (males) foci. Peribiliary fibrosis was also decreased. Clear cell foci in the liver were increased in females. Based on the results of these studies, ruxolitinib is not considered to be carcinogenic.
Utilization of Topical Ruxolitinib in Dermatology: A Review. [2023]As systemic administration of Janus kinase-inhibitors is associated with safety concerns, local alternatives, such as topical ruxolitinib, have been developed. This review summarizes utilization of topical ruxolitinib in dermatology. A literature search was performed of studies reporting topical use of ruxolitinib in dermatologic conditions. Twenty-four articles were included, representing 2618 patients. Results show improvement with topical ruxolitinib formulations in atopic dermatitis, vitiligo, psoriasis, and lichen planus. Results are conflicting in alopecia areata. Minimal bioavailability and low rates of mild-to-moderate treatment-related adverse events support a favorable safety profile and higher tolerability of topical ruxolitinib compared to oral Janus kinase-inhibitors.
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.
Pharmacological development in hidradenitis suppurativa. [2020]Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating disease of a relapsing nature which presents with nodules, abscesses, and suppurating lesions of intertriginous areas of the skin. Within recent years, there has been significant progress in terms of the treatment of HS, nevertheless, an unmet need of treatment exists and effective therapy remains a serious challenge. The current treatment strategies are focused on known pathomechanisms underlying and responsible for development of HS lesions, including hyperkeratinization and occlusion of pilosebaceous unit, dysbiosis and the extensive, chronic inflammation. Several cytokines (i.e. TNF-a, IL-1, IL-17, and IL-23) seem to be involved in HS pathogenesis, and their blockade appears as a rational therapeutic approach. So far TNF inhibition with adalimumab remains the only EMA-approved/FDA-approved agent in HS treatment and should be consequently considered first. Other drugs, however, play an increasing role in off-label therapy. In recent years, new phase II and III trials for HS management have appeared aimed at inhibition of specific targetable inflammatory pathways identified in HS. Thus, several new biologics are being investigated, including MABp1 (bermekimab), CJM112, bimekizumab, guselkumab, secukinumab, and IFX-1.
Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis. [2023]Background: Treatment of hidradenitis suppurativa (HS) is difficult and current guidelines are based mainly on expert opinion and non-randomized controlled trials. Recently, there have been some targeted therapies using uniform primary endpoints for outcome assessment. Objective: Recommendations can be provided on selecting biologics and targeted synthetic small molecules for refractory HS by comparing the efficacy and safety of these medications. Methods: Databases including ClinicalTrial.gov, Cochrane Library, and PubMed were searched. Randomized controlled trials (RCTs) for moderate-to-severe HS were eligible. We performed random-effect network meta-analysis and ranking probability. The primary outcome was Hidradenitis Suppurativa Clinical Response (HiSCR) at 12-16 weeks. Secondary outcome included Dermatology Life Quality Index (DLQI) 0/1, mean change of DLQI from baseline, and adverse effects. Results: A total of 12 RCTs involving 2915 patients were identified. Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w showed superiority to placebo in HiSCR at weeks 12 to 16. In addition, there was no significant difference between bimekizumab and adalimumab as measured by HiSCR (RR = 1.00; 95% CI: 0.66-1.52) and DLQI 0/1 (RR = 2.40, 95% CI: 0.88-6.50). In terms of ranking probability for achieving HiSCR at 12-16 weeks, adalimumab ranked first, followed by bimekizumab, secukinumab 300 mg q4w, and secukinumab 300 mg q2w. All biologics and small molecules did not differ in the development of adverse effects compared to placebo. Conclusions: Adalimumab, bimekizumab, secukinumab 300 mg q4w and secukinumab 300 mg q2w represent four regimens that produce better outcomes than placebo without increased risk of adverse events. Adalimumab and bimekizumab exhibited best HiSCR and DLQI 0/1 between weeks 12-16.
Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors. [2018]Hidradenitis suppurativa (HS) is a common inflammatory skin disease. Medical treatment is often disappointing and in severe disease surgery remains the therapy of choice. Extensive surgery may be effective but also mutilating. Patients experience a significant reduction in quality of life and the need for new treatment modalities are urgent. In recent years patients with HS have been treated off-label with tumour necrosis factor-alpha (TNF-alpha) inhibitors with a varying degrees of effect. We performed a systematic review of papers retrieved from two databases (PubMed and Web of Science) using the follow-ing keywords: hidradenitis suppurativa, acne inversa, infliximab, etanercept, and adalimumab. A total of 34 publications were retrieved, describing treatment of 105 patients. Most cases report treatment with infliximab (52/105). A positive treatment outcome was reported in 90/105 cases, with only 7/105 non-responders and 8/105 patients experiencing side-effects. The side-effects were comparable to those seen in other TNF-alpha inhibitor studies. In the majority of cases the treatment was effective when given as a suppressive therapy, but 15/105 cases were described with long-term remission (>or= 3 months) after the end of therapy. In most publications follow-up was, however, insufficient to allow a systematic exploration of this. TNF-alpha inhibitors seem to be effective in the treatment of HS. However, several questions remain to be answered through specific studies. This review has also identified a need for more standardized reporting of the outcomes as well as randomized controlled trials in this disease.