| Eligibility |
Inclusion Criteria:
1. Having been informed the purpose, nature, methods and possible adverse reactions of
the trial, the subjects agreed to be subjects and sign an informed consent form before
the start of any research process.
2. Part1(Phase ?b):Male and female subjects aged 18 to 65 (including 18 and
45).Part2(Phase ?):Male and female subjects aged 18 to 75 (including 18 and 45).
3. Atopic dermatitis with a diagnosis confirmed by a dermatologist (according to the
Hanifin and Rajka criteria); and also onset of symptoms at least 6 month prior to
screening visit.
4. Moderate to severe atopic dermatitis defined by an IGA score = 3,an EASI = 16, an
PP-NRS=4, and an BSA = 10% at the screening and baseline visit.
5. Documented history (within 6 mouths prior to the screening visit) of inadequate or
medically inadvisable response to topical corticosteroids (TCS), topical calcineurin
inhibitors (TCI), systematic treatment or phototherapy.
6. Twice daily use of an stable-dose, additive-free, bland emollient for at least 7 days
prior to Day 1, and continued for the duration of this trial.
7. Communicate well with investigators, understand and abide by requirements of this
trial.
Exclusion Criteria:
1. Have evidence of active or latent or inadequately treated infection with mycobacterium
tuberculosis (TB) as defined by investigators or specialist physicians according to
history, symptoms, signs, laboratory tests, T-SPOT test,and imagings, unless subjects
had previously received an adequate course of therapy at least 1 month.
2. History of mental disorders, genetic history of mental disorder, or epilepsy treated
by antipsychotics and sedatives.
3. In addition to AD, subjects who have current or recent history of clinically
significant severe immunologic/rheumatologic, cardiovascular, hepatic, renal,
gastrointestinal, or neurologic disease, or have a history of malignancies with the
exception of adequately treated or excised non-metastatic basal cell or squamous cell
cancer of the skin or cervical carcinoma in situ that might need systematic hormone
therapy or other interventions, may increase the risk defined by investigators.
4. In addition to AD, subjects have other dermatoses that affect the evaluation of trial
results, or have a wide range of tattoos, birthmarks, skin scars in the skin lesion
area.
5. Have a known immunodeficiency disorder or a first-degree relative with a hereditary
immunodeficiency.
6. Subjects who have received or are planning to receive an organ transplant operation
and are taking immunosuppressants, such as liver or kidney transplantation.
7. Any of the following abnormalities:
1. Within 3 months, subjects who have acute myocardial infarction, unstable angina
pectoris, coronary artery bypass grafting, or coronary stent implantation prior
to Day 1;
2. Have a history of severe arrhythmias, such as (Grade II type 2 or III ATV block,
long QT syndrome, or QTcF abnormalities: >470 ms in men and >480 ms in women);
3. Decompensated cardiac insufficiency (NYHA Class III or IV);
4. Other cardiac conditions that required treatment and are ineligible for the study
according to the investigator.
8. Infected with various viruses. For Hepatitis B, subjects who are Hepatitis B Surface
Antigen (HBsAg) or Hepatitis B Core Antibody (HBcAb) positive, and HBV-DNA positive
are not eligible for the study. For hepatitis C, subjects who are HCV antibody
positive is excluded. Subjects who are Human Immunodeficiency Viruses antibody or
Treponema pallidum antibody positive are also not eligible for the study.
9. Presence of any of the following laboratory abnormalities at the screening visit:
1. Part 1 (Phase ?b):
Fasting blood glucose>Upper limit of normal (ULN);Hypertension poorly controlled
by medication (Systolic pressure=150mmHg, Diastolic pressure=95mmHg);WBC,
Neutrophils, Lymphocyte count, Platelet count or Hemoglobin<lower limits of
normal (LLN);Serum creatinine>ULN or eGFR<60 mL/min;Total bilirubin, AST or ALT
values>ULN;PT or APTT values>ULN;
2. Part 2 (Phase ?):
Fasting blood glucose poorly controlled>10 mmol/L;Hypertension poorly controlled by
medication (Systolic pressure=160mmHg, Diastolic pressure=100mmHg);WBC<3.0×109/L,
Neutrophils<1.5×109/L; Lymphocyte count<0.8×109/L, Platelet count<100.0×109/L and
Hemoglobin<100 g/L;Serum creatinine>1.5 times the ULN or eGFR<40 mL/min;Total
bilirubin>1.5 times the ULN, AST or ALT values>2 times the ULN;PT or APTT values>1.5
times the ULN.
10. Have a clinical symptomatic infection requiring antimicrobial therapy, such as
bacteria, viruses, parasites or fungi during screening.
11. Have a history (single episode) of disseminated herpes zoster or disseminated herpes
simplex, or a recurrent (more than one episode ) of localized, dermatomal herpes
zoster.
12. Have a history of cerebral hemorrhage or cerebral infarction within 1 years prior to
Day 1.
13. Have a history of alcohol or substance abuse within 6 months prior to Day 1.
14. Have a history of hemorrhage (more than 400 mL), such as trauma, blood collection or
donation, or have a plan of blood donation during or after the study.
15. Have been treated by JAK inhibitors, such as Ruxolitinib, Tofacitinib, Baricitinib,
Filgotinib, Lestaurtinib, Pacritinib, Delgocitinib, Upadacitinib, or Abrocitinib,
within 3 months prior to Day 1.
16. Have been treated by biologicals of AD, such as Dupilumab, within 8 weeks or 5
half-live prior to Day 1, whichever is longer.
17. Have received grade 3 or 4 surgery within 8 weeks prior to Day 1.
18. Have been vaccinated with live or attenuated live vaccine within 4 weeks prior to Day
1.
19. Prior to Day 1, have joined any clinical trial of drug within 4 weeks (or 5 half-life
periods, depending on the longer one), or any clinical trial of medical apparatus and
instruments within 3 months.
20. Have been treated by any long-acting anticoagulant drugs, such as Warfarin,
Clopidogrel, or subjects who require continuous anticoagulant therapy, except for
Aspirin=100 mg per day.
21. Have a history of oral immune suppressants (eg, systemic corticosteroids, cyclosporine
A [CsA], mycophenolate-mofetil [MMF], interferon-? [IFN-?], azathioprine,
methotrexate) or Phototherapy (eg, UVB or PUVA) within 4 weeks or within 5 half-lives
(if known) prior to Day 1, whichever is longer.
22. Have received topical treatments that could affect atopic dermatitis (eg,
corticosteroids (TCS), calcineurin inhibitors (TCI), or PDE-4 inhibitors) within 2
weeks prior to Day 1.
23. Have received strong inhibitors or inducers of CYP3A Hepatic metabolic enzymes.
24. Subjects who are unable to take tablets, allergic to the active ingredient or
excipient of the investigational drug.
25. In the opinion of the investigator, subjects have a history of gastrointestinal
diseases that will affect the absorption of oral drugs, such as gastrointestinal
perforation.
26. Pregnant female subjects, breastfeeding female subjects, or male subjects able to
father children and female subjects of childbearing potential who are unwilling or
unable to use a highly effective method of contraception as outlined in this protocol
for the duration of the study and for at least 6 months after last use of
investigational drug.
27. Subjects who are unavoidable to or plan exposure to natural or artificial ultraviolet
(UV) radiation which could affect atopic dermatitis in the opinion of the
investigator.
28. In the opinion of the investigator, subjects who are not suitable to participate in
this clinical study.
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