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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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 Disease

Intervention / Treatment
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* 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, voluntarily participate in the trial, 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 32 kg/m2 (inclusive) at screening and baseline 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 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 the study drug. 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

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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) |