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The study will be conducted in 2 parts (SAD for Part 1 and MAD for Part2). Part 1 is a single-center, randomized, double-blind, placebo-controlled, SAD study to evaluate the safety, tolerability, immunogenicity, and PK of HS-20118 after a single oral dose in healthy participants.
Part 2 is a multi-center, randomized, double-blind, placebo-controlled, MAD study to evaluate the safety, tolerability, immunogenicity, PK, and PD of HS-20118 after multiple oral doses in patients with moderate to severe plaque psoriasis .
The study will be conducted in 2 parts (SAD for Part 1 and MAD for Part2). Part 1 is a single-center, randomized, double-blind, placebo-controlled, SAD study to evaluate the safety, tolerability, immunogenicity, and PK of HS-20118 after a single oral dose in healthy participants.
Part 1 will consist of 5 cohorts, i.e., X1 mg, X2 mg, X3 mg, X4 mg, and X5 mg dose cohorts (each cohort will include 3 participants to receive placebo). There will be no restriction on the male-to-female ratio. Each cohort will include 12 participants (HS-20118:placebo = 9:3), with a total of 60 participants. Participants will undergo PK blood sampling, ADA blood sampling, PD blood sampling and safety examinations during the study.
Part 2 is a multi-center, randomized, double-blind, placebo-controlled, MAD study to evaluate the safety, tolerability, immunogenicity, PK, and PD of HS-20118 after multiple oral doses in patients with moderate to severe plaque psoriasis.
Part 2 will tentatively consist of 6 cohorts ( HS-20118 vs placebo = 9:3), i.e., (1) A1 mg, (2) A2 mg, (3) A3 mg, (4) A4 mg, (5) A5 mg, (6) A6 mg. Each cohort will include 12 participants (HS-20118:placebo = 9:3), with a total of 72 participants. There will be no restriction on the male-to-female ratio. Participants will undergo PK blood sampling, ADA blood sampling, PD blood sampling and safety examinations during the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HS-20118 | Experimental | Single and multiple ascending doses of HS-20118 orally |
|
| placebo | Placebo Comparator | Single and multiple ascending doses of HS-20118-matched placebo orally |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HS-20118 | Drug | Single and multiple ascending doses of HS-20118 orally |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence, severity and association with the study drug of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation | adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Number of participants with abnormalities of physical examination | Physical examination includes skin, mucous membranes, lymph nodes, head, neck, chest, abdomen, and spine/limbs, etc. | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Number of participants with abnormalities of vital signs | Vital sign measured include body temperature, blood pressure, pulse, and respiratory rate. | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Number of participants with clinical laboratory abnormalities | Clinical laboratory tests include blood biochemistry test, hematology test, urinalysis, coagulation function test, etc. | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Number of participants with abnormalities of electrocardiogram (ECG) parameters | ECG parameters include heart rate, PR interval, RR interval, QRS duration, QTcF interval. | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum plasma concentration | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Tmax | Time to reach Cmax | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
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Inclusion Criteria:
For the SAD study:
For the MAD study:
Exclusion Criteria:
For the SAD study:
For the MAD study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kinetic Clinical Research | Not yet recruiting | Anaheim | California | 92806 | United States |
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| ID | Term |
|---|---|
| D011565 | Psoriasis |
| ID | Term |
|---|---|
| D017444 | Skin Diseases, Papulosquamous |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| HS-20118 placebo |
| Other |
Single and multiple ascending doses of HS-20118-matched placebo orally |
|
| AUC | Area under the plasma concentration-time curve | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| t½ | Terminal half-life | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| CL/F | Apparent clearance | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Vd/F | Apparent volume of distribution | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Rac | Accumulation ratio | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Incidence of Anti-drug antibody (ADA) | Anti-drug antibody (ADA) | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Proportions of psoriasis area and severity index (PASI) 75 | The PASI assessment will assess erythema, thickening (plaque evaluation, induration), and scaling (desquamation) on the head, trunk, upper limbs, and lower limbs, respectively | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Proportions of psoriasis area and severity index (PASI) 90 | The PASI assessment will assess erythema, thickening (plaque evaluation, induration), and scaling (desquamation) on the head, trunk, upper limbs, and lower limbs, respectively | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Proportions of psoriasis area and severity index (PASI) 100 | The PASI assessment will assess erythema, thickening (plaque evaluation, induration), and scaling (desquamation) on the head, trunk, upper limbs, and lower limbs, respectively | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Proportions of Investigator's Global Assessment (IGA) 0/1 | The investigator scores each of infiltration/hypertrophy (I), erythema (E), and scaling (S) as a whole | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Proportions of Investigator's Global Assessment (IGA) 0 | The investigator scores each of infiltration/hypertrophy (I), erythema (E), and scaling (S) as a whole | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Change from baseline in psoriasis area and severity index (PASI) total score | The PASI assessment will assess erythema, thickening (plaque evaluation, induration), and scaling (desquamation) on the head, trunk, upper limbs, and lower limbs, respectively | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Change from baseline in body surface area (BSA) | The total BSA affected by plaque psoriasis is estimated based on the percent area affected, including head, trunk, upper extremities, and lower extremities | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Change from baseline in dermatology life quality index (DLQI) | The DLQI is a 10-item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne, and viral warts | Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD) |
| Clinitiative - Floridian Clinical Research, LLC | Not yet recruiting | Miami Lakes | Florida | 33016 | United States |
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| NuLine Clinical Trial Center (Network) | Not yet recruiting | Pompano Beach | Florida | 33060 | United States |
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| Pacific Clinical Research Network (PCRN), Auckland | Recruiting | Takapuna | Auckland | 0622 | New Zealand |
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| Pacific Clinical Research Network (PCRN), Christchurch | Not yet recruiting | Christchurch | Christchurch | 8013 | New Zealand |
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| Momentum Clinical Research, Dunedin | Not yet recruiting | Dunedin | Dunedin | 9016 | New Zealand |
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| Momentum Clinical Research, Pukekohe | Not yet recruiting | Pukekohe | Pukekohe | 2120 | New Zealand |
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| Pacific Clinical Research Network (PCRN), Wellington | Not yet recruiting | Upper Hutt | Upper Hutt | 5018 | New Zealand |
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| Momentum Clinical Research, Wellington | Not yet recruiting | Mount Cook | Wellington Region | 6021 | New Zealand |
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