A Study of Phase Ⅰb/II to Evaluate the Safety, Efficacy and Pharmacokinetic Characteristics of QY201 Tablet in Subjects With Moderate to Severe Atopic Dermatitis
Overview
- Phase
- Phase 1
- Intervention
- QY201 placebo，BID
- Conditions
- Atopic Dermatitis
- Sponsor
- E-nitiate Biopharmaceuticals (Hangzhou) Co., Ltd.
- Enrollment
- 260
- Primary Endpoint
- Number of Participants With Treatment Emergent Adverse Events (AEs)- Phase Ⅰb
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase Ib/II, randomized, double-blind, placebo-controlled, parallel, multicenter study of a certain phase to evaluate the efficacy, safety, and pharmacokinetic characteristics of QY201 tablet in subjects in moderate to severe atopic dermatitis
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Part1（Phase Ⅰb）：Male and female subjects aged 18 to 65 (including 18 and 45).Part2（Phase Ⅱ）：Male and female subjects aged 18 to 75 (including 18 and 45).
- •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.
- •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.
- •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.
- •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.
- •Communicate well with investigators, understand and abide by requirements of this trial.
Exclusion Criteria
- •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.
- •History of mental disorders, genetic history of mental disorder, or epilepsy treated by antipsychotics and sedatives.
- •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.
- •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.
- •Have a known immunodeficiency disorder or a first-degree relative with a hereditary immunodeficiency.
- •Subjects who have received or are planning to receive an organ transplant operation and are taking immunosuppressants, such as liver or kidney transplantation.
- •Any of the following abnormalities:
- •Within 3 months, subjects who have acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, or coronary stent implantation prior to Day 1;
- •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);
- •Decompensated cardiac insufficiency (NYHA Class III or IV);
Arms & Interventions
Phase II Cohort4 (QY201 placebo)
50 subjects use QY201 placebo twice daily for 12 weeks
Intervention: QY201 placebo，BID
Phase Ib Cohort 2（5mg QY201 tablets or 5mg QY201 placebo）
8 subjects use 5mg QY201 tablets，2 subject uses 5mg QY201 placebo ，BID，29 days
Intervention: 5mg QY201 tablets or 5mg QY201 placebo,BID
Phase Ib Cohort 1（2mg QY201 tablets or 2mg QY201 placebo）
8 subjects use 2mg QY201 tablets，2 subject uses 2mg QY201 placebo ，BID，29 days
Intervention: 2mg QY201 tablets or 2mg QY201 placebo,BID
Phase Ib Cohort 3（10mg QY201 tablets or 10mg QY201 placebo）
8 subjects use 10mg QY201 tablets，2 subject uses 10mg QY201 placebo，QD，29 days
Intervention: 10mg QY201 tablets or 10mg QY201 placebo,QD
Phase Ib Cohort 4（10mg QY201 tablets or 10mg QY201 placebo）
8 subjects use 10mg QY201 tablets，2 subject uses 10mg QY201 placebo，BID，29 days
Intervention: 10mg QY201 tablets or 10mg QY201 placebo,BID
Phase Ib Cohort 5（15mg QY201 tablets or 15mg QY201 placebo）
8 subjects use 15mg QY201 tablets，2 subject uses 15mg QY201 placebo，BID，29 days
Intervention: 15mg QY201 tablets or 15mg QY201 placebo,BID
Phase Ib Cohort 6（20mg QY201 tablets or 20mg QY201 placebo）
8 subjects use 20mg QY201 tablets，2 subject uses 20mg QY201 placebo，BID，29 days
Intervention: 20mg QY201 tablets or 20mg QY201 placebo,BID
Phase II Cohort1 (5mg QY201 tablets)
50 subjects use 5mg QY201 tablets twice daily for 12 weeks
Intervention: 5mg QY201 tablets，BID
Phase II Cohort2 (10mg QY201 tablets)
50 subjects use 10mg QY201 tablets twice daily for 12 weeks
Intervention: 10mg QY201 tablets，BID
Phase II Cohort3 (20mg QY201 tablets)
50 subjects use 20mg QY201 tablets twice daily for 12 weeks
Intervention: 20mg QY201 tablets，BID
Outcomes
Primary Outcomes
Number of Participants With Treatment Emergent Adverse Events (AEs)- Phase Ⅰb
Time Frame: From the first administration to 28 days after the last administration of the study drug
Number of participants with treatment emergent adverse events (AEs) and change from baseline in vital signs (blood pressure, pulse rate, respiratory rate body temperature), physical examination, ECG parameters, clinical laboratory
Percentage of Participants Achieving >=75% Improvement From Baseline in Eczema Area and Severity Index (EASI75) Response at Week 12- Phase Ⅱ
Time Frame: Week 12
EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk and lower limbs ) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % BSA with AD in body region: 0 (0%), 1 (0 to 9%), 2 (10 to 29%), 3 (30 to 49%), 4 (50 to 69%), 5 (70 to 89%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, with higher scores indicating greater severity of AD.
Secondary Outcomes
- Percentage of Participants Achieving >=50%/75%/90% Improvement From Baseline in Eczema Area and Severity Index (EASI-50/EASI-75/EASI-90) Response at Week 2 and 4(Week 2 and 4)
- Pharmacokinetic parameters-Phase Ib(Day1 to Day 30)
- Number of Participants With Treatment Emergent Adverse Events (AEs)- Phase Ⅱ(From the first administration to 28 days after the last administration of the study drug)