A First in Human Study to Evaluate Safety, Tolerability, Pharmacology of HS-10374 in Healthy Subjects

A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HS-10374 in Healthy Subjects

The purpose of this first-in-human study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of HS-10374 in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: HS-10374 tablets; Drug: HS-10374-matched placebo tablets

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital affiliated to Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female subjects between the ages of 18-45 years
2. Have no reproductive potential; or agree to use a highly effective method of contraception, and refrain from donating sperm or eggs during the study period and for at least 6 months after last dosing
3. Have signed the informed consent form approved by the IRB

Exclusion Criteria:

1. Have a clinically significant infection currently or within past 30 days, or have a history of active tuberculosis; or have positive screening test for infectious disease, including tuberculosis, viral hepatitis, AIDS and syphilis
2. Have a history of or current allergic disease
3. Have a history of drug or alcohol abuse or currently positive test result(s) for alcohol or drugs of abuse
4. Smokers smoked ≥5 cigarettes per day within past 3 months or have a positive test result for nicotine
5. Clinically significant abnormal physical examination, vital signs, clinical laboratory values, ECGs or imaging tests
6. Pregnant or breastfeeding female subjects
7. Have received hormone-based contraceptives, drugs that prolong the QT interval, drugs that may cause drug interactions with investigational product, immunosuppressants, vaccines or other drugs within a specific period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HS-10374; Single and multiple ascending doses of HS-10374 orally	Drug: HS-10374 tablets; Single or multiple dosing of HS-10374 orally in a fasting state
Placebo Comparator: Placebo; Single and multiple ascending doses of HS-10374-matched placebo orally	Drug: HS-10374-matched placebo tablets; Single or multiple dosing of HS-10374-matched placebo orally in a fasting state

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity and association with the study drug of adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation		Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD)
Number of participants with clinical laboratory abnormalities	Clinical laboratory tests include hematology, urinalysis, stool analysis, blood chemistry, coagulation testing, Cystatin C, urine β2-microglobulin, erythrocyte sedimentation rate, C-reactive protein, etc.	Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD)
Number of participants with abnormalities of vital signs	Vital sign measured include blood pressure, pulse rate, temperature, and respiration rate.	Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (MAD)
Number of participants with abnormalities of physical examination	Physical examination includes assessments of general appearance, skin, lymph nodes, head, neck, lung, heart, abdomen, spine, extremities, nervous system, etc.	Day 1 up to Day 12 (SAD), Day 1 up to Day 42 (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 12 (SAD), Day 1 up to Day 42 (MAD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum plasma concentration	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
Tmax	Time to reach Cmax	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
AUC	Area under the plasma concentration-time curve	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
t½	Terminal half-life	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
CL/F	Apparent clearance	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
Vz/F	Apparent volume of distribution	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)
Rac	Accumulation ratio	Day 1 up to Day 6 (SAD), Day 1 up to Day 19 (MAD)

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jing Zhang, PhD, Huashan Hospital; Principal Investigator: Jinhua Xu, MD, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2021
• Primary Completion (Actual): March 24, 2023
• Study Completion (Actual): March 24, 2023

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: September 5, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: HS-10374-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No