A Trial of SHR-1703 in Healthy Subjects

Phase 1

Terminated

• Conditions: Asthma
• Interventions: Drug: SHR-1703; Drug: Placebo

• Registration Number: NCT04855591
• Lead Sponsor: Atridia Pty Ltd.

Brief Summary

This is a randomized, double-blind, placebo-controlled, single dose escalation phase 1 study. The objective of this study is to evaluate the safety, tolerability, pharmacokinetics pharmacodynamics and immunogenicity of subcutaneous administered SHR-1703 in healthy subjects.

Detailed Description

The study will consist of one dose esclation part with a total of 3 dose levels. The Subjects will be randomized to receive SHR-1703 as reflected by the guiding principle for the dose esclation/expansion phase. Each dose group includes a screening period, a baseline period, an observational period, and a safety follow-up period.

Study Timeline

• Study First Submitted: 2021-04-20
• Study First Submitted QC: 2021-04-20
• Study First Posted: 2021-04-22
• Study Start: 2021-06-14
• Primary Completion: 2021-09-13
• Status Verified: 2021-11
• Study Completion: 2021-11-18
• Last Update Submitted: 2021-11-18
• Last Update Posted: 2021-12-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

1. Healthy Caucasian subjects, male and female, 18 to 55 years of age, inclusive;
2. Body weight ≥45 kg (Both male and female), body mass index (BMI) between ≥19.0 and ≤29.9 kg/m2, inclusive;
3. No clinically significant abnormalities in medical history, general physical examination, vital signs, laboratory tests (hematology, urinalysis, blood chemistry and coagulation function) and ECG at the investigator's discretion during screening and baseline.
4. Men and women of childbearing potential (WOCBP) must agree to take effective contraceptive methods and have no plan to have a child from signing the consent form to 30-days after last scheduled follow-up visit.

Exclusion Criteria

1. Known history or suspected of being allergic to the study drug.
2. Positive hepatitis B virus (HBsAg), hepatitis C virus (HCV-Ab), human immunodeficiency virus (HIV-Ab) at screening.
3. Participation in clinical trials of other investigational drugs or medical devices within 3 months prior to screening or within 5 half-lives of any drugs during screening visit, or in the follow-up period of a clinical study whichever is longer
4. Use of any medicine within 4-weeks prior to the IP administration
5. Blood donation or loss of more than 400 mL of blood within 1 month of screening; or received blood transfusion within 2 months before screening.
6. Live (attenuated) vaccination within 1 month before screening or plan to be vaccinated
7. Severe injuries or major surgeries within 6 months before screening or plan to do surgeries during the trial
8. Patients with known or suspected parasitic infection within 6 months before screening
9. Either ALT, AST, ALP, GGT or total bilirubin level exceeds upper limit of normal range (ULN) at screening or baseline visits (confirmed by a single repeat, as per investigator's judgment)
10. More than 5 cigarettes daily (or products with equivalent amount of nicotine) for 3 months prior to screening.
11. History of alcohol abuse within 3 months prior to the IP administration

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SHR-1703 Dose Level 1	SHR-1703	Dose level 1 SHR-1703
SHR-1703 Dose Level 3	Placebo	Dose level 3 SHR-1703
SHR-1703 Dose Level 3	SHR-1703	Dose level 3 SHR-1703
SHR-1703 Dose Level 2	Placebo	Dose level 2 SHR-1703
SHR-1703 Dose Level 1	Placebo	Dose level 1 SHR-1703
SHR-1703 Dose Level 2	SHR-1703	Dose level 2 SHR-1703
SHR-1703 Dose Level 4 (optional)	SHR-1703	Dose level 4 SHR-1703 Additional dose escalations, as determined by the SMC depend on PK and safety data review
SHR-1703 Dose Level 4 (optional)	Placebo	Dose level 4 SHR-1703 Additional dose escalations, as determined by the SMC depend on PK and safety data review

Primary Outcome Measures

Name	Time	Method
Adverse events	Start of Treatment to end of study (approximately 34 weeks)	Incidence and severity of adverse events

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics-AUC0-last	Start of Treatment to end of study (approximately 34 weeks)	Area under the concentration-time curve from time 0 to last time point after SHR-1703 administration
Pharmacokinetics-Tmax	Start of Treatment to end of study (approximately 34 weeks)	Time to Cmax of SHR-1703
Pharmacokinetics-Cmax	Start of Treatment to end of study (approximately 34 weeks)	Maximum observed concentration of SHR-1703
Pharmacokinetics-CL/F	Start of Treatment to end of study (approximately 34 weeks)	Apparent clearance of SHR-1703
Pharmacokinetics-Vz/F	Start of Treatment to end of study (approximately 34 weeks)	Apparent volume of distribution during terminal phase of SHR-1703
Anti-drug-antibody	Start of Treatment to week 22 after IP administration	The percentage of subjects with positive ADA titers over time for SHR-1703
Pharmacokinetics-AUC0-inf	Start of Treatment to end of study (approximately 34 weeks)	Area under the concentration-time curve from time 0 to infinity after SHR-1703 administration
Pharmacokinetics-t1/2	Start of Treatment to end of study (approximately 34 weeks)	Terminal elimination half-life of SHR-1703
Pharmacodynamics-Eosinophils	Start of Treatment to end of study (approximately 34 weeks)	Absolute eosinophils account and change from baseline in percentage

Trial Locations

Locations (1)

Nucleus Network; 🇦🇺 Brisbane, Queensland, Australia