A Trial of SHR-1707 in Healthy Young Adult and Elderly Subjects

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Intravenous Administration of SHR-1707 in Healthy Young Adult and Elderly Subjects

A randomized, double-blind, placebo-controlled, single dose escalation phase 1 study to access the Pharmacokinetics and Pharmacodynamics of Single Intravenous Administration of SHR-1707

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: SHR-1707; Drug: Placebo

Detailed Description

The study will consist of two parts: Subjects will be randomized to receive SHR-1707 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): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2000
      • Atridia Pty Limited

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Ability to understand the trial procedures and possible adverse events, voluntarily participate in the trial,
2. Male or female aged between 18 years and 45 years (inclusive) at the date of signed consent form in Part 1 and aged between 55 years and 80 years (inclusive) in Part 2
3. Total body weight of 45~100 kg (inclusive), with a body mass index (BMI) of 19~32 kg/m2 (inclusive) at screening and baseline
4. Subjects with good general health, no clinically significant abnormalities, or have underlying disease which is believed to have minimal impact on the study treatment in elderly subjects
5. WOCBP agree to take effective contraceptive methods

Exclusion Criteria:

1. Severe injuries or surgeries within 6 months before screening
2. ALT, or AST or total bilirubin level <1.5x upper limit of normal range (ULN) at screening or baseline visits
3. QTcF > 450msec (Male), QTcF > 470msec (Female) in 12-lead ECG test during screening and baseline
4. Known history or suspected of being allergic to the study drug.
5. Use of any medicine within 14 days (including any prescription, or over-the-counter medicine, herbal remedy or nutritional supplement, except for vitamins and acetaminophen with recommended dose [The dose of acetaminophen should be less than 2g/day, and no more than 3 days for continuous use]), or within 5 half-lives
6. Live (attenuated) vaccination within 1 month before screening
7. Blood donation or loss of more than 400 mL of blood within 3 months; or received blood transfusion within 3 months before screening.
8. History of alcohol abuse in the past 12 months of screening
9. History of illicit or prescription drug abuse or addiction within 12 months of screening
10. More than 5 cigarettes daily for 12 months before screening
11. Participation in clinical trials of other investigational drugs (include placebo) or medical devices within 3 months prior to screening
12. Researchers and relevant staff of the research center or other persons directly involved in the implementation of the program

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-1707 Dose level 1; SHR-1707 or placebo is administered intravenous to young healthy subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion
Experimental: SHR-1707 Dose level 2; SHR-1707 or placebo is administered intravenous to young healthy subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion
Experimental: SHR-1707 Dose level 3; SHR-1707 or placebo is administered intravenous to young healthy subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion
Experimental: SHR-1707 Dose level 4; SHR-1707 or placebo is administered intravenous to young healthy subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion
Experimental: SHR-1707 Dose level 5; SHR-1707 or placebo is administered intravenous to young healthy subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion
Experimental: SHR-1707 Dose level 3 (Elderly subjects); SHR-1707 or placebo is administered intravenous to Elderly subjects	Drug: SHR-1707; SHR-1707 will be administered through IV infusion; Drug: Placebo; Placebo will be administered through IV infusion

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 12 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-1707 administration	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-AUC0-inf	Area under the concentration-time curve from time 0 to infinity after SHR-1707 administration	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-Tmax	Time to Cmax of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-Cmax	Maximum observed concentration of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-CL/F	Apparent clearance of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-Vz/F	Apparent volume of distribution during terminal phase of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics-t1/2	Terminal elimination half-life of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacokinetics MRT	Mean residence time of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Pharmacodynamics	Change from baseline of plasma biomarker concentrations	Start of Treatment to end of study (approximately 12 weeks)
Anti-Drug antibody	The percentage of subjects with positive ADA titers over time for SHR-1707.	Start of Treatment to end of study (approximately 12 weeks)

Collaborators and Investigators

• Sponsor: Atridia Pty Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Actual): March 21, 2022
• Study Completion (Actual): March 21, 2022

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: February 6, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: SHR-1707-I-101-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