Efficacy and Safety of Dupilumab in Combination With Tofacitinib in Moderate to Severe Adult AD Patients
NCT Number: NCT06465732
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Atopic Dermatitis
Interventions: DRUG: Dupilumab|DRUG: Tofacitinib
Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
Sex: ALL
Age: ADULT
Enrollment: 220
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: SINGLE (OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2025-01
Completion Date: 2026-07

Summary:
Atopic dermatitis (AD) is a common chronic inflammatory skin disease characterized by intense pruritus and sleep disturbances. The clinical manifestations of AD are varied, with the most basic features being dry skin, chronic eczema-like dermatitis, and intense pruritus. The prevalence in children and adults is about 30% and 10%, respectively. Most patients respond well to topical anti-inflammatory drugs, but approximately 10 percent of patients with moderate-to-severe AD require one or more systemic therapies to achieve good disease control. Although nonspecific immunosuppressive drugs (including glucocorticoids, cyclosporine A, methotrexate, azathioprine, or mycophenolate mofetil) are effective in alleviating or controlling these disorders to some extent, their overall efficacy in patients is limited and associated with significant side effects with long-term use.

The main hallmarks of systemic type II inflammation are eosinophilia and elevated serum immunoglobulin E (IgE) levels. Type II inflammatory response is not only associated with allergic reactions, but is also a driver of such diseases. The release of cytokines (interleukins 4, 5, and 13) in the response to type II inflammation can trigger a lymphocyte-mediated type II inflammatory response, inducing the onset and progression of allergic diseases. Reducing the inflammatory response by inhibiting the above-mentioned inflammatory factors is a potential therapeutic means for the treatment of allergic diseases represented by AD.

Investigational drug Dupilumab injection, an interleukin-4 receptor α (IL-4Rα) antagonist, is a human monoclonal antibody that binds IL-4Rα and inhibits IL-4 and IL-13 signaling. With a molecular weight of about 147 kDa, it inhibits the signaling of interleukin 4 and interleukin 13 and blocks its signaling pathway through the atopic binding of the interleukin 4Ra subunit shared with the interleukin 4 and interleukin 13 receptor complex, and blocks their signaling pathways, which can achieve continuous, efficient and safe improvement of skin lesions, itching and other symptoms and alleviate the condition.

Tofacitinib is a Janus kinase (JAK) inhibitor. JAK is an intracellular enzyme that conducts signals generated by cytokine or growth factor-receptor interactions on cell membranes, thereby affecting cell hematopoiesis and cellular immune function.

Primary Outcome Measures: Percentage of participants with a ≥75% reduction from baseline in Eczema Area and Severity Index (EASI) score (EASI-75) at 16 weeks, 16 weeks
Secondary Outcome Measures: Percentage of participants with an Investigator Global Scoring Method (IGA) score of 0 or 1 at W16, 16 weeks|Percentage of participants achieving EASI-75 at W12, 12 weeks|Percentage of participants with an IGA score of 0 or 1 at W12, 12 weeks|Percentage of participants achieving EASI-90 at W12, 12 weeks|Percentage of participants achieving EASI-90 at W16, 16 weeks|Percentage of participants with a ≥4-point reduction from baseline in the weekly mean of the Daily Peak Pruritus Numeric Assessment Scale (NRS) score at W12, 12 weeks|Percentage of participants with a ≥4-point reduction from baseline in the weekly mean of the Daily Peak Pruritus NRS score at W16, 16 weeks|Percentage of atopic dermatitis control tool (ADCT) score less than 7 at W12, 12 weeks|Percentage of atopic dermatitis control tool (ADCT) score less than 7 at W16, 16 weeks