A Trial of SHR-1703 in Healthy Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Dose-Escalation Study to Evaluate the Safety, Tolerability, PK, PD and Immunogenicity of Single Subcutaneous Administered SHR-1703 in Healthy Caucasian Subjects

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: SHR-1703; Drug: Placebo

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

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1703 Dose Level 1; Dose level 1 SHR-1703	Drug: SHR-1703; SHR-1703 will be administered subcutaneously; Drug: Placebo; Placebo of SHR-1703 will be administered subcutaneously
Experimental: SHR-1703 Dose Level 2; Dose level 2 SHR-1703	Drug: SHR-1703; SHR-1703 will be administered subcutaneously; Drug: Placebo; Placebo of SHR-1703 will be administered subcutaneously
Experimental: SHR-1703 Dose Level 3; Dose level 3 SHR-1703	Drug: SHR-1703; SHR-1703 will be administered subcutaneously; Drug: Placebo; Placebo of SHR-1703 will be administered subcutaneously
Experimental: SHR-1703 Dose Level 4 (optional); Dose level 4 SHR-1703 Additional dose escalations, as determined by the SMC depend on PK and safety data review	Drug: SHR-1703; SHR-1703 will be administered subcutaneously; Drug: Placebo; Placebo of SHR-1703 will be administered subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence and severity of adverse events	Start of Treatment to end of study (approximately 34 weeks)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Atridia Pty Ltd.
• Investigators: Principal Investigator: Dr Richard Friend, Nucleus Network

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2021
• Primary Completion (Actual): September 13, 2021
• Study Completion (Actual): November 18, 2021

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2021
• Last Update Submitted That Met QC Criteria: November 18, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: SHR-1703-104-AUS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No