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The goal of this clinical trial is to evaluate the safety, tolerability, PK, and PD of single and multiple ascending doses of QLS12010 Capsules and the effect of food on their PK profiles in healthy adult participants and participants with atopic dermatitis. This study consists of four parts: Part A is a single ascending dose (SAD) study, once sufficient safety and PK data are obtained from the SAD cohorts, the SMC will determine the dosage of initial cohort in Part B, which consists of three multiple ascending doses (MAD) cohorts of QLS12010 Capsules. Part C is a randomized, open-label, two-cycle, crossover food effect study under fasting and fed (high-fat meal) conditions. Part D is to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) characteristics, and preliminary efficacy of QLS12010 Capsules following multiple oral administrations in adult participants with atopic dermatitis (AD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single ascending dose cohorts in healthy participants | Experimental | Healthy volunteer subject cohorts randomized 6:2 receiving a single dose of QLS12010 or placebo. The starting dose will be 25 mg of QLS12010 or placebo. |
|
| Multiple ascending dose cohorts in healthy subjects | Experimental | Healthy volunteer subject cohorts randomized 8:2 to receive QLS12010 or placebo QD for 14 continuous days. The starting dose of QLS12010 or placebo is based on upcoming data from SAD part. |
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| Food Effect Cohort in healthy subjects | Experimental | Part C is a two-cycle, crossover study under fasting and fed (high-fat meal) conditions. In Cycle 1, 12 healthy adult participants will be randomly divided into two groups on D-1, with 6 participants in each group receiving a single oral dose of QLS12010 Capsules under fasting or fed conditions, respectively. After completing washout, they will receive crossover administration for the Cycle 2 study. |
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| Early Efficacy in patients with AD | Experimental | Part D of the study plans to enroll 12 adults with moderate to severe atopic dermatitis (AD). Eligible subjects (after screening) will be sequentially assigned to two dose groups (Dose 1 and Dose 2) in the order of their enrollment. Enrollment of Dose 2 may commence only after Dose 1 has completed enrollment of 6 subjects. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| QLS12010 | Drug | QLS12010 oral capsule(s) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Incidence and severity of treatment emergent Adverse Events as assessed by CTCAE v5.0 | up to approximately 1 month |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the curve plasma concentration from time zero to last measurable concentration [AUC(0-last)] | up to approximately 1 month | |
| Area under the curve plasma concentration from time zero to infinity [AUC(0-∞)] | up to approximately 14 days |
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Inclusion Criteria for Parts A-C:
Inclusion Criteria for Part D:
General Exclusion Criteria:
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Haiyan Li, M.D. | Contact | (+86) 18600489179 | haiyanli1027@hotmail.com | |
| Wenhui Wang, M.D. | Contact | (+86) 15611908751 | wwh0608@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University Third Hospital | Recruiting | Beijing | China |
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| Placebo | Drug | Matching placebo oral capsule(s) |
|
| Maximum observed plasma concentration (Cmax) | up to approximately 1 month |
| Time to maximum observed plasma concentration (Tmax) | up to approximately 1 month |
| Terminal elimination half-life (t1/2) | up to approximately 1 month |
| Apparent clearance (CL/F) | up to approximately 1 month |
| Apparent volume of distribution (Vz/F) | up to approximately 1 month |
| Mean residence time (MRT) | up to approximately 1 month |
| Changes and percentage changes from baseline in Eczema Area and Severity Index (EASI) scores | The minimum EASI score is 0, and the maximum EASI score is 72. A score of 0 indicates clear or no eczema; a greater score indicates more severe disease. | at Weeks 1, 2, 3, 4, 5, and 6 |
| Changes and percentage changes from baseline in Investigator's Global Assessment (IGA) scale | The IGA5-point scale ranges from 0 (clear) to 4 (severe AD). A decrease in score indicates an improvement in signs and symptoms. | at Weeks 1, 2, 3, 4, 5, and 6 |
| Changes and percentage changes from baseline in weekly mean scores of Peak Pruritus Numerical Rating Scale (PP NRS) | The PP NRS is a single self-reported item designed to measure peak pruritus, or 'worst' itch, over the previous 24 h based on the following question: 'On a scale of 0 to 10, with 0 being "no itch" and 10 being "worst itch imaginable". | at Weeks 1, 2, 3, 4, 5, and 6 |
| Changes and percentage changes from baseline of body surface area (BSA) affected by lesions | BSA assessment estimates the area of skin lesions in each part of the body, with one palm unit of the patient taken as 1% of the body surface area. | at Weeks 1, 2, 3, 4, 5, and 6 |
| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| D017497 | Hidradenitis Suppurativa |
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D017192 | Skin Diseases, Bacterial |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D012874 | Skin Diseases, Infectious |
| D013492 | Suppuration |
| D016575 | Hidradenitis |
| D013543 | Sweat Gland Diseases |
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
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