Efficacy and Safety of Stapokibart for Primary Cutaneous Amyloidosis

Prior treatment

• Use of any of the following treatments within 4 weeks prior to randomization: a. Immunosuppressants or immunomodulators, such as systemic corticosteroids, cyclosporine, mycophenolate mofetil, interferon gamma (IFN-γ), azathioprine, methotrexate, and Janus kinase (JAK) inhibitors; b. UV phototherapy; c. Systemic traditional Chinese medicine (TCM) treatment.
• Use of topical corticosteroids (TCS), topical calcineurin inhibitors (TCI), TCM, or phosphodiesterase 4 (PDE-4) inhibitors within 2 weeks prior to randomization.
• Receipt of anti-IL-4R monoclonal antibodies, anti-IgE monoclonal antibodies, or other biologics within 12 weeks or 5 half-lives (whichever is longer) prior to randomization.
• Receipt of live attenuated vaccines within 12 weeks prior to randomization or planned vaccination during the study period.
• Use of antihistamines within 1 week prior to randomization (subjects who have been on a stable dose of antihistamines for at least 7 days prior to randomization and plan to continue during the study period may be included).
• Receipt of allergen-specific immunotherapy (desensitization therapy) within 6 months prior to randomization.
• Previous receipt of at least 12 consecutive doses of anti-IL-4Rα or IL-13 monoclonal antibodies with inadequate clinical response (defined as failure to achieve AASI 50 during treatment).
• Positive for Treponema pallidum antibody during the screening period (subjects who have undergone standard treatment and have a negative non-treponemal antigen serological test may participate in the study).
• Participation in another clinical trial of a drug or medical device within 12 weeks prior to randomization.
• Presence of chronic active or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 4 weeks prior to randomization. After resolution of the infection, the subject may be re-screened once.
• Subjects who plan to undergo major surgical procedures during the study period.

Other illness

• History of known or suspected immunosuppression (immunodeficiency), including a history of invasive opportunistic infections (such as histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis), even if the infection has resolved; or unusual frequency, recurrence, or chronicity of infections (at the investigator's discretion).
• Subjects with any type of active malignancy or a history of malignancy (except for cervical cancer that has been cured for more than 5 years prior to the screening period, or non-metastatic squamous cell carcinoma of the skin, basal cell carcinoma, and papillary thyroid cancer).
• Presence of active Mycobacterium tuberculosis infection.
• Presence of active hepatitis during the screening period, or positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) and HBV-DNA, or positive for hepatitis C virus (HCV) antibody and HCV-RNA.
• Positive for HIV antibody during the screening period, or history of HIV infection.
• Subjects with a history of alcoholism, drug abuse, or known drug dependence.
• History of atopic keratoconjunctivitis involving the cornea.
• Any medical or psychiatric conditions that the investigator deems would pose a risk to the subject, interfere with participation in the study, or confound the interpretation of study results.

Lab values

• Subjects with severe liver or kidney function impairment during the screening period, such as aspartate aminotransferase or alanine aminotransferase \>2 times the upper limit of normal (ULN), total bilirubin \>1.5 times ULN, serum creatinine \>1.2 times ULN, etc.

Other

• Presence of any skin comorbidities that may interfere with study assessments, including but not limited to scabies, cutaneous T-cell lymphoma, psoriasis, etc.
• Presence of any other significant medical history that the investigator deems would pose a risk to the subject's safety or be poorly controlled if the subject participates in the study, in addition to PCA.
• Pregnant or breastfeeding women.

• Males or females aged 18 to 75 years, with a diagnosis of PCA confirmed by skin biopsy, and an IGA score of ≥3, a AASI score of ≥5, and a BSA involvement of ≥5%.
• Subjects who have received at least 4 weeks of mid-to-high potency or at least 2 weeks of very high potency topical corticosteroids (TCS) or an adequate course of systemic corticosteroids within the 6 months prior to screening, but with an inadequate response; or subjects who are unable to receive the above treatments due to adverse reactions or potential risks.
• Prior to the first dose, subjects must have used a moisturizer continuously for at least 1 week, once daily, and must continue to use it throughout the study period.
• Able to understand and complete study-related questionnaires.
• Able to read, understand, and are willing to sign the informed consent form.
• Willing and able to comply with study visits and related procedures.
• Women of childbearing potential must agree to use contraception (such as intrauterine devices, oral contraceptives, or condoms) during the study and for 6 months after the study ends; must have a negative serum pregnancy test within 7 days before the first dose and must not be breastfeeding; male subjects must agree to use contraception during the study and for 6 months after the study ends.