Efficacy and Safety of Dupilumab in Combination With Tofacitinib in Moderate to Severe Adult AD Patients

NCT06465732 | Not Yet Recruiting Phase 4

• 1 other identifier: IR2024072
• Study Type: interventional
• Target: 220
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Atopic Dermatitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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

Study Arms (2)

dupilumab plus tofacitinib

EXPERIMENTAL

this arm receives dupilumab injection and oral tofacitinib.

Drug: Dupilumab; Drug: Tofacitinib

dupilumab mono

ACTIVE COMPARATOR

this arm receives dupilumab treatment only.

Drug: Dupilumab

Interventions

Dupilumab DRUG

the active comparator arm receive dupilumab only

dupilumab mono; dupilumab plus tofacitinib

Tofacitinib DRUG

the experimental arm receive dupilumab plus tofacitinib.

dupilumab plus tofacitinib

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Have the ability to understand the content of the research and voluntarily sign the ICF.
• years old≤ age ≤ 60 years old (calculated from the date of signing the ICF), male or female.
• The diagnosis of AD at screening meets the consensus criteria for dermatology in the United States (2014) (see Appendix), and the disease has been in condition for ≥ half a year before screening, and all of the following conditions are met at screening and randomization:
• A. EASI score ≥ 12 points at screening and randomization; B. IGA score ≥ 3 points at screening and randomization (0-4 points IGA scale, 3 points are moderate, 4 points are severe); C. AD involvement of BSA ≥10% at screening and randomization; D. Weekly average of daily peak pruritus NRS score at randomization ≥ 4 points.
• Subjects of childbearing potential and their partners agree to use effective contraceptive measures throughout the study period (from signing the ICF to 3 months after the last study drug administration) .
• Able to communicate well with the investigator and comply with the follow-up requirements of the protocol.

You may not qualify if:

• Subjects with any of the following cannot be enrolled in this study:
• Allergy to any ingredient in dupilumab or tofacitinib, or allergy or intolerance to other oral JAK inhibitors.
• Use of any of the following medications or treatments:
• Received treatment with other oral JAK inhibitors within 1 month prior to baseline, or lack of efficacy/intolerance to other oral JAK inhibitors in the past, including but not limited to baricitinib, upadatinib and abuxitinib;
• Use of excessive pilumab within 6 weeks prior to baseline;
• Within 3 months (or within 5 drug half-lives, whichever is longer) prior to baseline, use of other systemic biologics other than dupilumab that are known or likely to affect AD (such as IL-13 receptor antibody \[tracilumab\], IL-31Rα antibody \[nimolizumab\], etc.);
• Within 4 weeks (or within 5 half-lives, whichever is longer) prior to baseline, have used any kind of systemic therapy for AD: immunosuppressants (such as cyclosporine, methotrexate, azathioprine, mycophenolate mofetil, etc.), glucocorticoids, PDE-4 inhibitors, etc.;
• Treatment with phototherapy (narrowband ultraviolet B \[NBUVB\], ultraviolet B \[UVB\], ultraviolet A1 \[UVA1\], psoralen + ultraviolet A \[PUVA\]), tanning bed, or any other luminescent device within 4 weeks prior to baseline;
• Allergen-specific immunotherapy (desensitization therapy) within 6 months prior to baseline;
• Vaccination with any live vaccine or live attenuated vaccine within 12 weeks prior to baseline; or anticipated need to receive a live or live attenuated vaccine during the study, including at least 12 weeks after the last dose of the investigational drug;
• Treatment with any drug or medical device clinical study within 3 months prior to baseline or within 5 half-lives of the drug (whichever is longer, if known), or currently enrolled in another interventional study.
• Laboratory abnormalities that meet any of the following criteria during the screening period:
• Hemoglobin \< 90.0 g/L;
• White blood cell count\< 2.5×109/L;
• Neutrophil count\< 1.5×109/L;

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

MeSH Terms

Conditions

Dermatitis, Atopic

Interventions

dupilumab; tofacitinib

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Central Study Contacts

Xiaoyong Man, PhD

CONTACT

13600516219; manxy@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 20, 2024
• Study Start: January 1, 2025
• Primary Completion: November 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: June 20, 2024

Record last verified: 2024-03