A Study to Evaluate the Efficacy and Safety of CBP-201 in Moderate to Severe Atopic Dermatitis in China

This study is a randomized, double-blind, multi-center, controlled study designed to assess the efficacy, safety and PK characteristics of CBP-201 in eligible subjects with moderate to severe AD.

The study includes a screening period, a treatment period and a follow-up period. The treatment period is divided into two stages.

Inclusion criteria

• 12≤ age ≤75 years at the screening visit, male or female;
• Diagnosed with atopic dermatitis (according to the American Academy of Dermatology's Guidelines of care for the management of atopic dermatitis, 2014[1]) at the screening, visit and:

a) The subject has been suffering from the disease for more than 1 year at the time of screening, and according to the judgment of the investigator, the subject has had poor response to topical drugs such as corticosteroids, phosphodiesterase-4 (PDE-4) inhibitors or calcineurin inhibitors (TCI), or it is not medically suitable for the subject to receive topical drug treatment (e.g., there are important side effects or safety risks);

Note: Poor response is defined as any of the following conditions:

i. The patient has not achieved and maintained response or reached a low disease activity state (equivalent to IGA 0=asymptomatic to 2=mild) despite regular use of topical therapy during the 1 year before baseline; ii. The patient has received systemic treatment for AD despite regular use of topical therapy during the 1 year before baseline.

b. At the screening and baseline visit, Investigator's Global Assessment (IGA) score ≥3 (according to the validated Investigator Global Assessment for Atopic Dermatitis [vIGA-AD™] scale, see Section 17.4 Appendix D), Eczema Area and Severity Index (EASI) score≥16 (see Section 17.5, Appendix E), and≥10% body surface area (BSA) of AD involvement(see Section 17.6, Appendix F); c. The average score of the maximum pruritus intensity in the Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 (see Section 17.1, Appendix A).

Note: The baseline average score of maximum pruritus intensity in the PP-NRS will be calculated based on the average value of the maximum pruritus intensity in the PP-NRS score [daily score range 0-10] every day within 7 days before randomization. In these 7 days, the scores of at least 4 days are required for the calculation of the baseline average score. If the patient's reporting days are less than 4 days in the 7 days before the planned date of randomization, randomization should be postponed until the requirements are met, but it is not allowed to exceed the maximum screening period of 28 days.

• Able and willing to use a stable dose of a mild emollient at the AD involvement area twice a day starting from at least 7 days before baseline and continue to use it during the study period (see Section 8.1.1.2 Emollients).
• Female subjects of childbearing potential (FCBP) and male subjects who have not undergone vasectomy must take highly effective contraceptive measures during the entire study period, including the 8-week follow-up period after discontinuation of study drug. Postmenopausal women (determined by testing follicle stimulating hormone [FSH]) and women with a record of surgical sterilization (i.e., tubal ligation or hysterectomy or bilateral oophorectomy) before the screening visit can be considered infertile.

Highly effective contraceptive measures include:

i. Abstinence (acceptable only if it is part of the subject's routine lifestyle); ii. Hormones (oral, patch, ring, injection, implant) combined with male condoms. This measure must be used at least 30 days before the first study drug administration. Otherwise, another acceptable method of contraception must be used; iii. Intrauterine device (IUD) combined with male condoms; iv. Exceptions are: a) women who have had amenorrhea for at least 12 consecutive months without using drugs known to cause amenorrhea, and have a recorded FSH level greater than 40 mIU/mL or in the postmenopausal range; or b) surgical sterilization (e.g., hysterectomy, bilateral oophorectomy).

• Subjects and/or their guardians have the ability to learn the study requirements and process, and voluntarily take part in the clinical trial and sign an informed consent form (ICF); note: for subjects ≥18 years: subjects voluntarily agree to take part in the study by themselves and sign ICF; for subjects aged 12-17 years: subjects and their guardians voluntarily agree to take part in the study, the guardians sign the ICF, and the subjects sign the informed assent form for minors by themselves.
• Subjects and/or their guardians are willing and able to comply with study visits and related procedures.

Exclusion criteria

• Patients who have received any of the following treatments:

• Treatment with dupilumab or any anti-IL-4Rα or IL-13 antibodies;
• Topical drugs for treatment of AD or have the potential to affect the assessment of AD, including but not limited to corticosteroids, PDE-4 inhibitors, Janus kinase (JAK) inhibitors, aromatic hydrocarbon receptor agonists, tacrolimus or pimecrolimus, or traditional Chinese medicine (TCM) or herbal medicine, etc. within 2 weeks before baseline;
• Have undergone bleaching baths ≥ twice within 2 weeks before baseline;
• Have begun to use prescription emollients or emollients containing additives (e.g., ceramide, hyaluronic acid, urea, or filaggrin breakdown products) to treat AD from the screening period (if the subject has started using this kind of emollient before the screening visit, they can continue to use it at a stable dose; if the subject is intolerable to the emollients provided uniformly by the sponsor during the screeing period, he/she can change to emollient of this kind used previously, but it must be used at a stable dose for at least 7 days before baseline and during the study period);
• Treatment with systemic corticosteroids or other immunosuppressive/immunomodulating substances (e.g., cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, or oral JAK inhibitors) due to AD or other diseases within 4 weeks before baseline (except for corticosteroid inhalers and nasal sprays);
• Treatment with systemic TCM or herbal treatment within 4 weeks before baseline (note: except for those for the treatment of diseases other than AD, which are necessary and will neither increase the risks of the subjects nor affect the assessment of the study in accordance with the medical judgements of the investigator and/or specialist physician);
• Treatment with phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), sunbed or any other light emitting device (LED) therapy within 4 weeks before baseline;
• Have used any investigational drug/treatment within 4 weeks before baseline or 5 drug half-lives, whichever is longer;
• Treatment with other biological agents (e.g., omalizumab) within 3 months before baseline or 5 drug half-lives (if known), whichever is longer;
• Have been vaccinated with live (attenuated) vaccine within 8 weeks before baseline;
• Treatment with cell depletion agents (e.g., rituximab) within 6 months before baseline;
• Treatment with allergen specific immunotherapy (SIT) within 6 months before baseline (except those who were already on stable-dose therapy before baseline).

Eligibility criteria Inclusion criteria

Patients must meet all of the following criterias to be enrolled into this study:

• Patients who meet any of the following:

• History of hypersensitivity to L-histidine, trehalose or Tween 80;
• Other skin complications in addition to AD that may interfere with the study assessments;
• Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC);
• History of malignant tumor within 5 years before screening, except for cervical carcinoma in situ or non-metastatic cutaneous squamous cell carcinoma or basal cell carcinoma;
• Active tuberculosis (TB) at the screening visit, latent tuberculosis or a history of non-tuberculous Mycobacterium infection

Note:

• Unless there is a clear specialist record proving that the patient has received adequate treatment and is currently able to start receiving biological treatment (based on the medical judgment of the investigator and/or infectious disease specialist);
• If necessary, T-spot test may be used for auxiliary diagnosis of suspected tuberculosis patients; f. Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb) and HBV-DNA, or positive for hepatitis C antibody and HCV RNA polymerase chain reaction; or serologically positive for human immunodeficiency virus (HIV) at the screening visit; g. Any of the following laboratory test abnormalities at the screening visit: i. Aspartate aminotransferase or alanine aminotransferase > 2 times the upper limit of normal (ULN), or total bilirubin > 1.5×ULN ii. Serum creatinine > 1.2×ULN iii. Hemoglobin < 8.5 g/dl (85.0 g/L) in male patients and < 8.0 g/dl (80.0 g/L) in female patients iv. White blood cell count <3.0×109/L or ≥14×109/L v. Platelet count <100×109/L h. Planning to undergo major surgical operations during the study period; i. Used systemic treatment with antibiotics, antiviral drugs, antiparasitic drugs, antigenic drugs, or antifungal drugs due to infection within 4 weeks before the baseline visit, or suffered from superficial skin infection (e.g., impetigo) within 2 weeks before baseline (after the infection subsides, the subjects can be rescreened); j. History of parasite infection (e.g., helminth) within 6 months before baseline; k. According to the investigator's judgment, there is a known or suspected history of immunosuppression within 6 months before baseline, including a history of invasive opportunistic infections, such as aspergillosis, coccidiosis, histoplasmosis, HIV, listeriosis, Pneumocystis or tuberculosis, even if the infection has subsided; or there is an abnormally frequently recurrent or persistent infection; l. History of alcohol or drug abuse within 2 years before the screening visit; m. Any other medical or psychological condition (including clinically significant laboratory test abnormalities, ECG parameters, etc.) at the screening visit, which, as judged by the investigator, may indicate new and/or insufficiently understood diseases, may put the patient at an unreasonable risk due to his/her participation in the clinical trial, may lead to unreliable results of the patient's participation, or may interfere with the study assessments. The specific reasons for patients excluded due to this criterion will be indicated in the study documents (medical records, eCRF, etc.).
• Pregnant or lactating women, or subjects with pregnancy or lactation plans during the study period.