GSK1070806 for Eczema
(AtDvance Trial)
Recruiting in Palo Alto (17 mi)
+90 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: GlaxoSmithKline
Must not be taking: Topical medications
Disqualifiers: Uncontrolled diseases, Pregnancy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?The study is designed to evaluate the long-term safety and efficacy of GSK1070806 in participants with moderate-to severe atopic dermatitis, who have completed phase 2b parent GSK atopic dermatitis (AtD) study (NCT05999799).
Will I have to stop taking my current medications?
The trial requires that you stop using certain topical medications for eczema, like topical corticosteroids and calcineurin inhibitors, at least one week before starting the study. The protocol does not specify about other medications, so it's best to discuss your current medications with the study team.
What data supports the effectiveness of the drug GSK1070806 for eczema?
Research shows that interferon-gamma, a component related to GSK1070806, has been effective in improving symptoms of severe atopic dermatitis (eczema) by reducing skin redness, dryness, and thickening. This improvement is linked to its ability to decrease excessive immune cell activation.
12345Is GSK1070806 safe for humans?
Research on similar treatments like recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis shows that it is generally safe, with some patients experiencing flu-like symptoms but no severe side effects.
34678How does the drug GSK1070806 work differently for eczema?
GSK1070806 is unique because it targets interleukin-18 (IL-18), a protein involved in the immune response that is elevated in eczema patients, potentially reducing inflammation by modulating immune cell activity differently than standard treatments like antihistamines or tacrolimus.
246910Eligibility Criteria
This trial is for individuals with moderate to severe atopic dermatitis who completed the Phase 2 study (NCT05999799) and may benefit from further treatment. Participants must be able to attend clinic visits, use electronic devices for questionnaires, and women of childbearing potential must follow strict contraceptive guidelines and have negative pregnancy tests.Inclusion Criteria
Participants must sign and date the consent document.
I am not pregnant or breastfeeding and follow the required birth control guidelines.
Be intentional and able to visit the doctor at the clinic by appointment and follow all procedures related to research studies and questionnaires (able to read and understand Patient-reported outcomes (PRO) questionnaires and be able to use electronic devices).
+5 more
Exclusion Criteria
I haven't used certain skin medications for a week.
Permanent discontinuation of the study drug at any time during GSK's qualifying Phase 2 AtD (NCT05999799) or a medical condition that would hinder GSK's participation in the Phase 2 219538 (NCT05999799) AtD research project.
Systemic therapy is not suitable for my condition.
+4 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive GSK1070806 at various doses to evaluate long-term safety and efficacy
280 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Open-label extension
Participants continue to receive GSK1070806 to assess long-term outcomes
Long-term
Participant Groups
The long-term safety and effectiveness of GSK1070806 are being tested in patients with atopic dermatitis who previously participated in a related Phase 2b study. The goal is to see how well this drug works over an extended period.
4Treatment groups
Experimental Treatment
Group I: GSK1070806 Dose 4Experimental Treatment1 Intervention
Participants will receive GSK1070806 Dose 4.
Group II: GSK1070806 Dose 3Experimental Treatment1 Intervention
Participants will receive GSK1070806 Dose 3.
Group III: GSK1070806 Dose 2Experimental Treatment1 Intervention
Participants will receive GSK1070806 Dose 2.
Group IV: GSK1070806 Dose 1Experimental Treatment1 Intervention
Participants will receive GSK1070806 Dose 1.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
GSK Investigational SiteW. Lake Hills, TX
GSK Investigational SiteCanoga Park, CA
GSK Investigational SiteSanta Monica, CA
GSK Investigational SiteFountain Valley, CA
More Trial Locations
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Who Is Running the Clinical Trial?
GlaxoSmithKlineLead Sponsor
References
[Interleukin-18 and new drugs. Protective effect against tumor growth and infections]. [2006]IL-18, originally identified as interferon-gamma inducing factor (IGIF), is related to the IL-1 family in terms of its structure as well as its processing, receptor, signal transduction pathway and pro-inflammatory properties. IL-18 is also functionally related to IL-12, as it induces the production of Th1 cytokines and participates in cell-mediated immune cytotoxicity. A summary is made of recent advances in the understanding of IL-18 structure, processing, receptor expression and immunoregulatory functions. It focuses on the role of IL-18 modulation in tumours, infections and autoimmune and inflammatory diseases.
[Clinical significance of serum interleukin-18 concentration in the patients with atopic dermatitis]. [2019]Interleukin (IL)-18, a potent inducer of interferon gamma (IFN-gamma), is known to have a role in diseases involving type-2 T helper cell responses including atopic dermatitis. In this study, we aimed to determine the clinical significance of serum IL-18 level in the patients with atopic dermatitis.
Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. [2011]Interferon-gamma (IFN-gamma) is a potent cytokine that modulates IL-4-induced immune responses. Atopic dermatitis is associated with increased IgE levels and decreased IFN-gamma production. Recent phase I and phase II studies have suggested that short-term rIFN-gamma therapy is effective in the treatment of severe atopic dermatitis.
[Human recombinant interferon gamma in the treatment of atopic dermatitis]. [2017]Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. We have studied the efficacy of recombinant human interferon gamma (rhINF-gamma) administered subcutaneously at a dose of 0.05 mg/m2 in ten patients with severe AD. Patients were treated for 4 weeks. They have shown marked clinical improvement starting from the third week of treatment. The efficacy of the drug varied, with erythema, dryness and lichenification being the most responsive symptoms. There was no change in serum immunoglobulin E and IgG4 levels. Whole blood eosinophil count decreased only transiently and was accompanied by a tendency to lower values of serum eosinophil cationic protein. Patient with AD showed an increased expression of a T-cell surface activation marker CD 25 as compared to healthy controls. Moreover, clinical improvement was roughly paralleled by the decrease in this T-cell activation marker. We conclude that rhINF-gamma is a novel efficacious therapeutic approach in severe AD. We suggest that its primary action might be related to the inhibition of T-cell activation.
Interferon-gamma in the treatment of atopic dermatitis: influence on T-cell activation. [2019]Atopic dermatitis (AD) is a chronic relapsing skin disease characterized by various immunologic abnormalities. Its pathogenesis remains obscure and its treatment difficult. We have studied the efficacy of systemic recombinant human interferon-gamma (rhIFN-gamma) treatment (0.05 mg/m2 sc on 3 consecutive days, during 4 weeks) in 10 patients with severe AD. Marked clinical improvement was observed starting from the third week of treatment. Erythema, dryness, and lichenification were the most responsive symptoms. Serum immunoglobulin E and IgG4 levels did not change during treatment. Blood eosinophil count decreased only transiently at the end of the first and second series of injections (days 4 and 11; P = 0.02). Patients with AD showed an increase in CD25-positive cells (11.0% vs 4.88%; P = 0.0001) as compared to 10 age-matched healthy controls. Moreover, in parallel with clinical improvement, a distinct decrease in CD25-positive lymphocytes was observed on days 32 and 50 (P = 0.002 and P = 0.006, respectively). We suggest that in AD the beneficial effect of rhIFN-gamma might be related to the inhibition of excessive T-cell activation, perhaps of the subpopulations, producing interleukin (IL)-4 and IL-5.
IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. [2023]Atopic eczema (AE) is a chronic relapsing inflammatory skin disease where the commensal yeast Malassezia can act as a microbial trigger factor. Malassezia activates human DC to produce IL-18, an innate cytokine that is elevated in serum of AE patients; however, the precise role of IL-18 in human AE etiology is unknown. Herein, we investigated the effect of IL-18 on the human invariant NKT (iNKT) cell compartment in AE. We found that IL-18 was a potent activator of human iNKT-cells and promoted a pro-inflammatory CD1d-dependent response, even in the absence of exogenous ligands. Chronic activation via IL-18 on the other hand was inhibitory and skewed the iNKT-cell pool by selectively suppressing CD4(+) iNKT-cells. This was mimicked in AE patients where the proportion of CD4(+) iNKT-cells was reduced in peripheral blood and coincided with elevated plasma levels of IL-18. Furthermore, a reduced CD4(+) iNKT-cell pool was associated with elevated IgE levels in plasma, and the plasma levels of IL-18 correlated with both total IgE and disease severity in the AE patients. Based on these findings, we propose that IL-18-mediated activation and subsequent dysregulation of the CD1d-restricted iNKT-cells plays a role in the pathogenesis of human AE.
Interferon-alpha therapy in atopic dermatitis. [2021]Thirteen patients with a severe adult form of atopic dermatitis (AD) received 3.0 x 10(6) IU of recombinant interferon-alpha 2a (rIFN-alpha 2a) 3 times a week. A satisfactory response was obtained in 5 of them. Serum IgE levels in all 13 patients remained unchanged throughout the study. Flu-like symptoms were common, but clinical or laboratory adverse effects were otherwise slight. The moderately beneficial therapeutic effects observed in this study support a possible role for IFN-alpha in controlling immunologic deficiencies in atopic dermatitis.
IL-4 Augments IL-31/IL-31 Receptor Alpha Interaction Leading to Enhanced Ccl 17 and Ccl 22 Production in Dendritic Cells: Implications for Atopic Dermatitis. [2020]Severe pruritus is a characteristic feature of atopic dermatitis (AD) and is closely related to its activity. Recent studies have shown that IL-31 is a key determinant of pruritus in AD. Anti-IL-31 receptor alpha (IL-31RA) antibody treatment has also been reported to improve pruritus clinically, subsequently contributing to the attenuation of AD disease activity. Therefore, IL-31 has been thought to be an important cytokine for regulating pruritus and AD disease activity; however, how IL-31 is involved in the immune response in AD has remained largely unknown. Epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) derived from bone marrow cells have been reported to play a critical role in AD pathogenesis. LCs and DCs produce Ccl 17 and Ccl 22, which chemoattract Th2 cells, leading to AD development. Therefore, we aimed to clarify how IL-31/IL-31RA interaction affects Ccl 17 and Ccl 22 production. To test this, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-4, an important cytokine in AD development. We found that IL-31RA expression was upregulated by IL-4 stimulation in a dose-dependent manner in BMDCs. Furthermore, IL-31 upregulates Ccl 17 and Ccl 22 production in the presence of IL-4, whereas IL-31 stimulation alone did not produce Ccl 17 and Ccl 22. These findings suggest that IL-4 mediates IL-31RA expression and IL-31/IL-31RA interaction augments Ccl 17 and Ccl 22 production in BMDCs, which promotes Th2-deviated immune response in AD. Since we previously reported that soybean tar Glyteer, an aryl hydrocarbon receptor (AHR) ligand, impairs IL-4/Stat 6 signaling in BMDCs, we examined whether Glyteer affects IL-31RA expression induced by IL-4 stimulation. Glyteer inhibited upregulation of IL-31RA expression induced by IL-4 stimulation in a dose-dependent manner. Glyteer also inhibited Ccl 17 and Ccl 22 production induced by IL-4 and IL-31 stimulation. Taken together, these findings suggest that Glyteer treatment may improve AD disease activity by impairing IL-31/IL-31RA interaction in DCs.
An unexpected increase in circulating IFN-gamma by cyclosporin A in atopic patients: a discrepancy between in vitro and in vivo events. [2019]Defective interferon gamma (IFN-gamma) production has been suggested to be relevant to immunologic abnormalities observed in atopic dermatitis (AD). We describe two patients with severe AD who were treated with oral cyclosporin A (Cy-A) and in whom the serum levels of IL-1 alpha, IFN-gamma and tumor necrosis factor alpha (TNF-alpha) were sequentially measured. Cy-A, known to inhibit IFN-gamma production in vitro, caused a rapid rise in serum IFN-gamma, but not Il-1 alpha and TNF alpha, levels in the patients and the IFN-gamma levels appeared to be inversely related to the therapeutic efficacy. The observed increase in serum IFN-gamma levels during Cy-A therapy may have contributed to a marked clinical improvement of the AD.
Atopic dermatitis and alpha-chemokines. [2019]Many studies have shown the involvement of interferon (IFN)γ-inducible protein 10 (IP-10) and T-helper 1 (Th1) cytokines in Atopic Dermatitis (AD). IFN-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-18 are potent stimulators of the expression and secretion of IP-10 in cultured keratinocytes from AD patients. Apoptosis of keratinocytes, induced mainly by T cells and mediated by IFN-γ, is the essential pathogenetic event in eczema formation. Enhanced IP-10, induced by IFN-γ, and IFN-inducible T cell alpha-chemoattractant (I-TAC) expression has been observed in lesional AD skin. It has been shown that keratinocytes undergoing apoptosis in acute eczematous lesions release chemokines that attract more T cells toward the epidermis, which may further augment the inflammation and keratinocyte apoptosis. Drugs used in the treatment of AD modulate IP-10. Antihistamines are widely used for the treatment of AD; it has been shown in human monocyte-derived dendritic cells (MoDCs) and autologous CD4+ T cells that antihistamines inhibited the production of IP-10 and�� monokine induced by IFN-gamma (MIG) expressions. It has been also shown that antimycotics and tacrolimus suppress the induced production of IP-10 in human keratinocytes.