Evaluate Efficacy and Safety of Repeat Subcutaneous Doses of FB825 in Adults With Moderate-to-Severe Atopic Dermatitis

This multicenter, randomized, double-blind, placebo-controlled, 2-arm, parallel-group study will enroll approximately 90 subjects with moderate-to-severe atopic dermatitis, with approximately 45 subjects per group.

The study duration of subject participation in the study is up to 28 weeks, including up to 4 weeks for screening, a 12-week study intervention and a 12-week follow-up period after study intervention. The study treatment will be administered as 5 SC doses.

Inclusion criteria

Subjects must meet all of the following criteria to be included in the study:

• The subject is male or female between 18 and 65 years of age at the time of giving informed consent.
• Body weight equal to or greater than 40 Kg at the time of screening.
• The subject has a physician-confirmed diagnosis of moderate-to-severe atopic dermatitis based on 12 months history of symptoms designated by Hanifin and Rajka criteria.
• Eczema Area and Severity Index (EASI) score ≥16 at screening and baseline visits.
• Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score ≥ 3 (5-point scale) at the screening and baseline visits.
• ≥10 % body surface area (BSA) of AD involvement at the screening and baseline visits.
• Baseline pruritus numerical rating scale (NRS) average score for maximum itch intensity of ≥ 3, based on the average of daily pruritus NRS scores for maximum itch intensity reported during the 7 days prior to randomization.
• History of inadequate response to a stable (4 weeks) regimen of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) as treatment for AD within 6 months before the screening visit. (The TCS should belong to medium to high potency strength and has been applied for at least 4 weeks or for the maximum duration recommended by product prescribing information.)

• An inadequate response is defined as the inability to achieve and maintain remission or a low disease activity state (comparable to vIGA-AD 0=clear to 2=mild).
• Subjects with systemic treatment for AD in the past 6 months were also considered as inadequate responders to topical treatments.
• Patients must be applying stable doses of an additive-free, basic bland emollient twice-daily for at least 1 week immediately before the baseline visit.

Note: See exclusion criterion #13 for limitations regarding emollients.

• Female subjects must have a negative serum pregnancy test at screening. All subjects of childbearing potential and his/her sexual partner must meet 2 following condition or acceptable methods of birth control throughout the study.

• Oral, injectable, or implanted hormonal contraceptives
• Condom with a spermicidal form, gel, film, cream, or suppository
• Occlusive cap (diaphragm or cervical/vault caps) with a spermicidal foam, gel, film, cream, or suppository
• Intrauterine device
• Intrauterine system (for example, progestin-releasing coil) or be surgically sterile (i.e., hysterectomy, bilateral tubal ligation, bilateral oophorectomy, or vasectomy)
• Postmenopausal (defined as amenorrhea 12 consecutive months and documented serum follicle stimulating hormone level per laboratory standard) Note: The subject must utilize the method of effective contraception during study period as well as 16 weeks or 5 half-lives following the last dosing of FB825.
• The subject is able to provide written informed consent.
• The subject agrees to and is capable of adhering to scheduled visits, the treatment plan, laboratory tests, other study procedures, and all protocol requirements.

Exclusion criteria

• Subjects to whom any of the following applies will be excluded from the study:

• Female subjects who are pregnant or lactating
• The subject with positive test results for HBeAg or HCV RNA should be excluded as they are indications of active hepatitis B virus and hepatitis C virus replication.
• A positive human immunodeficiency virus (HIV) test (e.g., HIV Ag/Ab combo test) at screening or a history of HIV infection.
• The subject has a history of alcohol or drug abuse within one year prior to screening that would impair or risk the patients' full participation in the study, in the opinion of the investigator.
• The subject has a clinically significant, currently active or severe gastrointestinal, cardiovascular, nervous system, psychiatric, metabolic, renal, hepatic, respiratory (with the exception of uncomplicated allergic rhinitis and allergic asthma), inflammatory, immunological, endocrine, diabetes, obesity [BMI≥35] or infectious disease and is ineligible to participate in the study as judged by the investigator.
• The subject has a clinically significant history, as determined by the investigator, of drug allergies or hypersensitivity such as, but not limited to, sulfonamides and penicillin, or a drug allergy witnessed in a previous study with experimental drugs.
• The subject has any history of a previous anaphylactic reaction.
• The subject has any condition that, in the opinion of the investigator, would compromise the study or the well-being of the subject or prevent the subject from meeting or performing study requirements.
• The subject has received TCS or TCI within 7 days prior to the baseline visit (Day 1).
• The subject has received any immunoglobulin products or blood products within 3 months prior to baseline visit.
• The subject has received a biologic product (including investigational biologic product) within 5 half-lives or 3 months, whichever is longer, before baseline visit.
• The subject has received an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before baseline visit.
• Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period.
• Initiation of treatment of AD with sedative anti-histamine products during the screening period (patients may continue using stable doses of non-sedative anti-histamine).
• The subject is a member of the professional or ancillary personnel involved in the study.
• The subject regular use (≥2 visits per week) of a tanning booth/parlor within 4 weeks prior to the baseline visit.
• The subject has received cell-based immunotherapy treatment within 3 months prior to baseline visit.
• The subject has used any of the following classes of medication (prescription or over-the-counter) within specific time frames before the study drug treatment:

• Systemic corticosteroids within 4 weeks.
• Leukotriene modifiers within 4 weeks.
• Cyclosporine within 4 weeks, or other immunosuppressants (e.g. gold salts, methotrexate, azathioprine) within 4 weeks.
• IFN-γ within 12 weeks, or other immunomodulating drugs within 4 weeks.
• Allergen immunotherapy within 1 year.
• JAK inhibitor within 4 weeks.
• The subject has received phototherapy within 4 weeks before the study drug treatment.
• The subject has received live vaccine within 12 weeks before the study drug treatment.
• The subject has presence of skin comorbidities that may interfere with study assessments.
• The subject has known or suspected history of immunosuppression, including history of opportunistic infections (e.g., TB) per investigator's judgment.
• The subject has active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit.

Note: Patients with resolved infection may be rescreened.

• The subject has history of malignancy within 5 years before the screening period, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.
• The subject has planned or anticipated the use of any prohibited medications and procedures during the entire study period.
• The subject has planned or anticipated major surgical procedure during the entire study period.
• High risk of parasite infection. Evidence of parasitic infection designated as having the following two items:

• Risk factors for parasitic disease include living in an endemic area, experiencing chronic gastrointestinal symptoms, traveling to regions where geohelminthic infections are endemic within the last 6 months, and/or having chronic immunosuppression).

AND

• Evidence of parasitic colonization or infection found during stool evaluation for ova and parasites.

Note: stool ova and parasite evaluation will only be conducted in patients with risk factors and an eosinophil count more than twice the upper limit of normal.