A Study 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

The study is being conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single intravenous administration of SHR-1707 in healthy young adult and elderly subjects.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Ability to understand the trial procedures and possible adverse events, be able and willing to provide a written informed consent
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 19~28 kg/m2 (inclusive)
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. Positive hepatitis B virus (HBsAg), hepatitis C virus (HCV-Ab), or human immunodeficiency virus (HIV-Ab) at screening
3. ALT, or AST or total bilirubin level <1.5x upper limit of normal range (ULN) at screening or baseline visits
4. QTcF > 450msec (Male), QTcF > 470msec (Female) in 12-lead ECG test during screening and baseline
5. Known history or suspected of being allergic to Aβ antibody
6. 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
7. Live (attenuated) vaccination within 1 month before screening
8. Blood donation or loss of more than 400 mL of blood within 3 months; or received blood transfusion within 3 months before screening.
9. History of alcohol abuse in the past 12 months of screening
10. History of illicit or prescription drug abuse or addiction within 12 months of screening
11. More than 5 cigarettes daily for 12 months before screening
12. Participation in clinical trials of other investigational drugs (include placebo) or medical devices within 3 months prior to screening
13. Researchers and relevant staff of the research center or other persons directly involved in the implementation of the program
14. The instigators determined that other conditions were inappropriate for participation in this clinical trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A single dose of SHR-1707 by intravenous infusion in healthy young adults.	Drug: SHR-1707; A single dose of SHR-1707 by intravenous (IV) infusion in healthy young adults.; Drug: SHR-1707; A single dose of SHR-1707 by intravenous (IV) infusion in elderly subjects.
Placebo Comparator: placebo in healthy young adults.	Drug: Placebo; A single dose of matching SHR-1707 placebo by intravenous (IV) infusion in healthy young adults.; Drug: Placebo; A single dose of matching SHR-1707 placebo by intravenous (IV) infusion in elderly subjects.
Experimental: A single dose of SHR-1707 by intravenous infusion in elderly subjects.	Drug: SHR-1707; A single dose of SHR-1707 by intravenous (IV) infusion in healthy young adults.; Drug: SHR-1707; A single dose of SHR-1707 by intravenous (IV) infusion in elderly subjects.
Placebo Comparator: placebo in elderly subject	Drug: Placebo; A single dose of matching SHR-1707 placebo by intravenous (IV) infusion in healthy young adults.; Drug: Placebo; A single dose of matching SHR-1707 placebo by intravenous (IV) infusion in elderly subjects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability	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
Area under the concentration-time curve from time 0 to last time point (AUC0-last) after SHR-1707 administration	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)
Area under the concentration-time curve from time 0 to infinity (AUC0-inf) after SHR-1707 administration	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)
Time to Cmax (Tmax) of SHR-1707	Time to Cmax of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Maximum observed concentration (Cmax) of SHR-1707	Maximum observed concentration of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Terminal elimination half-life (t1/2) of SHR-1707	Terminal elimination half-life of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Clearance (CL) of SHR-1707	Clearance of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Volume of distribution (Vss) of SHR-1707	Volume of distribution of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
Mean residence time (MRT) of SHR-1707	Mean residence time of SHR-1707	Start of Treatment to end of study (approximately 12 weeks)
The change from baseline in plasma Aβ40 and Aβ42 concentrations	The change from baseline in plasma Aβ40 and Aβ42 concentrations will be measured to determine the degree of change over time.	Start of Treatment to end of study (approximately 12 weeks)
Number of subjects with Anti-SHR-1707 antibodies	Number 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: Shanghai Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2021
• Primary Completion (Actual): January 13, 2022
• Study Completion (Actual): January 13, 2022

Study Registration Dates

• First Submitted: June 8, 2021
• First Submitted That Met QC Criteria: July 21, 2021
• First Posted (Actual): July 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 18, 2023
• Last Update Submitted That Met QC Criteria: May 16, 2023
• Last Verified: May 1, 2023

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-1707-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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