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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: SHR-1707
* Drug: Placebo
* Drug: SHR-1707
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand the trial procedures and possible adverse events, be able and willing to provide a written informed consent 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 Total body weight of 45 100 kg (inclusive), with a body mass index (BMI) of 19 28 kg/m2 (inclusive) 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 WOCBP agree to take effective contraceptive methods Exclusion Criteria: Severe injuries or surgeries within 6 months before screening Positive hepatitis B virus (HBsAg), hepatitis C virus (HCV-Ab), or human immunodeficiency virus (HIV-Ab) at screening ALT, or AST or total bilirubin level <1.5x upper limit of normal range (ULN) at screening or baseline visits QTcF > 450msec (Male), QTcF > 470msec (Female) in 12-lead ECG test during screening and baseline Known history or suspected of being allergic to Aβ antibody 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 Live (attenuated) vaccination within 1 month before screening Blood donation or loss of more than 400 mL of blood within 3 months; or received blood transfusion within 3 months before screening. History of alcohol abuse in the past 12 months of screening History of illicit or prescription drug abuse or addiction within 12 months of screening More than 5 cigarettes daily for 12 months before screening Participation in clinical trials of other investigational drugs (include placebo) or medical devices within 3 months prior to screening Researchers and relevant staff of the research center or other persons directly involved in the implementation of the program The instigators determined that other conditions were inappropriate for participation in this clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: SHR-1707 compared with placebo
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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) |