Clinical trial NCT06846710: Evaluate the Safety and Pharmacokinetics/Pharmacodynamics of HS-20118
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of HS-20118 in Adult Participants
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Psoriasis
Keywords: Psoriasis
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-02-26
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 .

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

For the SAD study:

1. Healthy adults aged 18-45 years (inclusive) at the time of signing the informed consent form;
2. Male participants weighing ≥ 50 kg and female participants weighing ≥ 45 kg, both ≤ 110 kg; body mass index (weight/square of height (kg/m2)) within the range of 18-28 kg/m2 (inclusive);
3. Normal results or abnormal results but without clinical significance in comprehensive examinations, including general physical examination, vital signs, laboratory tests, 12-lead ECG, abdominal color Doppler ultrasound, and chest X-ray from the frontal and lateral position ;

For the MAD study:

1. Male or female participants aged 18-65 years (inclusive) at the time of signing the informed consent form;
2. Male participants weighing ≥ 50 kg and female participants weighing ≥ 45 kg, both ≤ 110 kg;
3. Chronic plaque psoriasis for at least 6 months with or without psoriatic arthritis;

Exclusion Criteria:

For the SAD study:

1. Participants with immune-related diseases and medical history at screening;
2. Participants with a history of drug or other allergies who are considered by the investigator to be at high risk for participating in this study, or who may be allergic to the investigational medicinal product or any component of the investigational medicinal product as judged by the investigator;
3. History of drug abuse within the past 5 years or use of illicit drugs within 3 months before the study; or positive for urine drug screening;

For the MAD study:

1. Guttate psoriasis, pustular psoriasis, erythrodermic psoriasis, drug-induced psoriasis, or other diseases that affect the treatment results;
2. Current use of illicit drugs or prior use of illicit drugs within the specific time periods;
3. Known history of recurrent or chronic infections, or prior history of chronic or recurrent infections, including but not limited to: chronic renal infection, chronic chest infection (e.g., bronchiectasis), symptomatic urinary tract infection, and open, draining, or infected skin wounds; history of serious infections (e.g., sepsis, pneumonia, and pyelonephritis), or hospitalization or treatment with intravenous antibiotics for infections within 2 months before screening;

Primary outcomes:
measure: Incidence, severity and association with the study drug of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Number of participants with abnormalities of physical examination
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Number of participants with abnormalities of vital signs
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Number of participants with clinical laboratory abnormalities
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Number of participants with abnormalities of electrocardiogram (ECG) parameters
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
Secondary outcomes:
measure: Cmax
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Tmax
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: AUC
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: t½
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: CL/F
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Vd/F
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Rac
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Incidence of Anti-drug antibody (ADA)
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Proportions of psoriasis area and severity index (PASI) 75
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Proportions of psoriasis area and severity index (PASI) 90
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Proportions of psoriasis area and severity index (PASI) 100
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Proportions of Investigator's Global Assessment (IGA) 0/1
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Proportions of Investigator's Global Assessment (IGA) 0
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Change from baseline in psoriasis area and severity index (PASI) total score
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Change from baseline in body surface area (BSA)
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
measure: Change from baseline in dermatology life quality index (DLQI)
timeFrame: Day 1 up to Day 36 (SAD), Day 1 up to Day 71 (MAD)
Other outcomes:
Locations:
Study officials:
References: