GSK1070806 for Eczema

(AtDvance Trial)

Recruiting at 90 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Must not be taking: Topical medications

Disqualifiers: Uncontrolled diseases, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 280 weeks

79 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{3 4 6 7 8}

How 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. ^{2 4 6 9 10}

Eligibility 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).

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.

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

Treatment Details

Interventions

• GSK1070806

Trial Overview 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.

Participant Groups

Group I: GSK1070806 Dose 4 Experimental Treatment 1 Intervention

Participants will receive GSK1070806 Dose 4.

Group II: GSK1070806 Dose 3 Experimental Treatment 1 Intervention

Participants will receive GSK1070806 Dose 3.

Group III: GSK1070806 Dose 2 Experimental Treatment 1 Intervention

Participants will receive GSK1070806 Dose 2.

Group IV: GSK1070806 Dose 1 Experimental Treatment 1 Intervention

Participants will receive GSK1070806 Dose 1.

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Findings from Research

IL-18 is a pro-inflammatory cytokine that plays a crucial role in the immune response by inducing Th1 cytokines and enhancing cell-mediated immune cytotoxicity, making it important in fighting tumors and infections.

Recent research has advanced our understanding of IL-18's structure, processing, and receptor interactions, highlighting its potential as a target for therapeutic modulation in autoimmune and inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Interleukin-18 and new drugs. Protective effect against tumor growth and infections]. Wollheim, FA.[2006]

Patients with atopic dermatitis have significantly higher serum levels of IL-18 compared to healthy individuals, indicating its potential role in the disease's pathology (332 pg/mL vs 151 pg/mL).

Serum IL-18 levels correlate with the severity of atopic dermatitis, suggesting it could be an independent predictor of disease severity, although its clinical utility as a test needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical significance of serum interleukin-18 concentration in the patients with atopic dermatitis]. Park, DS., Youn, YH.[2019]

Long-term treatment with recombinant interferon-gamma (rIFN-gamma) for severe atopic dermatitis in 15 patients over a minimum of 22 months resulted in significant improvements, with total body surface area involvement decreasing from 61.6% to 18.5%.

The therapy was found to be safe, with no significant laboratory abnormalities or growth issues reported, while also leading to a reduction in clinical severity scores from 11.4 to 6.3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. Schneider, LC., Baz, Z., Zarcone, C., et al.[2011]

In a study of 10 patients with severe atopic dermatitis (AD) treated with recombinant human interferon gamma (rhINF-gamma) for 4 weeks, significant clinical improvement was observed starting from the third week, particularly in symptoms like erythema, dryness, and lichenification.

The treatment appears to work by inhibiting T-cell activation, as indicated by a decrease in the T-cell activation marker CD 25, while serum immunoglobulin levels and eosinophil counts showed little change, suggesting a targeted mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human recombinant interferon gamma in the treatment of atopic dermatitis]. Musiał, J., Milewski, M., Undas, A., et al.[2017]

In a study of 10 patients with severe atopic dermatitis, treatment with systemic recombinant human interferon-gamma (rhIFN-gamma) led to significant clinical improvement starting from the third week, particularly in symptoms like erythema, dryness, and lichenification.

The mechanism of action appears to involve the inhibition of excessive T-cell activation, as evidenced by a decrease in CD25-positive lymphocytes, suggesting that rhIFN-gamma may help regulate immune responses in atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-gamma in the treatment of atopic dermatitis: influence on T-cell activation. Musiał, J., Milewski, M., Undas, A., et al.[2019]

IL-18 is a strong activator of human invariant NKT (iNKT) cells, promoting a pro-inflammatory response that may contribute to the development of atopic eczema (AE).

In patients with AE, elevated levels of IL-18 correlate with a reduced population of CD4(+) iNKT cells and higher IgE levels, suggesting that IL-18 may play a significant role in the disease's pathogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. Lind, SM., Kuylenstierna, C., Moll, M., et al.[2023]

In a study of 13 patients with severe atopic dermatitis, treatment with recombinant interferon-alpha 2a (rIFN-alpha 2a) resulted in a satisfactory response in 5 patients, suggesting potential efficacy in managing the condition.

While flu-like symptoms were common, the treatment was generally well-tolerated with minimal clinical or laboratory adverse effects, indicating a favorable safety profile for rIFN-alpha 2a in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interferon-alpha therapy in atopic dermatitis. Torrelo, A., Harto, A., Sendagorta, E., et al.[2021]

IL-31 plays a crucial role in promoting pruritus and atopic dermatitis (AD) by enhancing the production of Ccl 17 and Ccl 22 in dendritic cells when stimulated by IL-4, indicating its importance in the immune response associated with AD.

Glyteer, a soybean tar compound, can inhibit the IL-4-induced expression of IL-31RA and subsequently reduce the production of Ccl 17 and Ccl 22, suggesting it may be a potential treatment to improve AD by disrupting the IL-31/IL-31RA signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Miake, S., Tsuji, G., Takemura, M., et al.[2020]

In two patients with severe atopic dermatitis (AD) treated with oral cyclosporin A (Cy-A), there was a rapid increase in serum interferon gamma (IFN-gamma) levels, which is known to be inhibited by Cy-A in laboratory settings.

The rise in IFN-gamma levels during treatment appeared to correlate with significant clinical improvement in AD, suggesting that this increase may play a role in the therapeutic effects of Cy-A.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An unexpected increase in circulating IFN-gamma by cyclosporin A in atopic patients: a discrepancy between in vitro and in vivo events. Shiohara, T., Sagawa, Y., Nagashima, M.[2019]

Interferon (IFN)γ and T-helper 1 (Th1) cytokines play a crucial role in Atopic Dermatitis (AD) by stimulating the expression of IP-10 in keratinocytes, which contributes to inflammation and keratinocyte apoptosis.

Treatment options for AD, such as antihistamines, antimycotics, and tacrolimus, can effectively modulate IP-10 levels, potentially reducing inflammation and improving symptoms in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atopic dermatitis and alpha-chemokines. Di Bari, F.[2019]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

[Interleukin-18 and new drugs. Protective effect against tumor growth and infections]. [2006]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

[Clinical significance of serum interleukin-18 concentration in the patients with atopic dermatitis]. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Long-term therapy with recombinant interferon-gamma (rIFN-gamma) for atopic dermatitis. [2011]

4. Poland pubmed.ncbi.nlm.nih.gov

[Human recombinant interferon gamma in the treatment of atopic dermatitis]. [2017]

5. Denmark pubmed.ncbi.nlm.nih.gov

Interferon-gamma in the treatment of atopic dermatitis: influence on T-cell activation. [2019]

6. Germany pubmed.ncbi.nlm.nih.gov

IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema. [2023]

7. Sweden pubmed.ncbi.nlm.nih.gov

Interferon-alpha therapy in atopic dermatitis. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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]

9. Sweden pubmed.ncbi.nlm.nih.gov

An unexpected increase in circulating IFN-gamma by cyclosporin A in atopic patients: a discrepancy between in vitro and in vivo events. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

Atopic dermatitis and alpha-chemokines. [2019]