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Safety, Tolerability and Pharmacodynamics of SHR-1707 in Alzheimer's Disease Patients.

Primary Purpose

Alzheimer's Disease

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
SHR-1707
SHR-1707 placebo
Sponsored by
Shanghai Hengrui Pharmaceutical Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Alzheimer's Disease

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age ≥55and ≤85 on the date of signing the informed consent, males or females; BMI≥19kg/m2 and ≤32 kg/m2, weight ≥45 kg且≤100 kg at screening or baseline; must meet the diagnostic criteria for MCI due to AD or mild AD; The total score of HAMD-17 should be ≤10 scores at screening and baseline; The score of Hachinski ischemic scale should be ≤4 scores at screening and baseline; Qualitative amyloid PET scan results from the central laboratory confirmed the presence of pathological changes in AD; Agreed to test ApoE genotype; Have a stable caregiver; where symptomatic drugs for AD is used, they must be stable for at least 3 months prior to the baseline visit; Exclusion Criteria: Cognitive impairment of subjects due to other medical or neurological factors (other than AD); History of stroke or transient ischemic attack, seizures, or other unexplained loss of consciousness within the past year; Any psychiatric diagnosis that may interfere with the subject's cognitive assessment; Cannot tolerate MRI or has contraindications to MRI, has significant lesions shown on MRI during screening, or has other conditions that the investigator believes may bring a significant risk to the subject; Suspected allergy to Aβ antibody drugs and excipients. Patients who had severe trauma or had undergone surgery within 6 months prior to screening, or were scheduled to undergo surgery during the trial; History of moderate (3b) or severe renal failure or insufficiency; Uncontrolled hypertension: systolic blood pressure > 160mmHg and diastolic blood pressure >100mmHg in supine position during screening or baseline; 12-lead ECG showed QTcF >450ms for male and >470ms for female during screening; History of hypoglycemic coma or uncontrolled diabetes 6 months prior to the screening period; Thyroid dysfunction; Had unstable or clinically significant cardiovascular disease within 1 year prior to the screening period, had or currently has atrial fibrillation; History of malignancy within 5 years prior to screening; Patients with clinically significant systemic immunosuppression due to the persistent effects of immunosuppressive drugs; Human immunodeficiency virus antibody (HIV-Ab), treponema pallidum antibody and hepatitis C virus antibody (HCV-Ab) were positive during screening.Hepatitis B active subjects [Hepatitis B virus surface antigen (HBsAg) positive with HBV DNA > upper limit of normal] Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times ULN, or total bilirubin exceeding 2 times ULN Folic acid or vitamin B12 below the lower limit of normal coagulation disorders According to the investigators, the subjects were suicidal or had committed suicidal behavior in the six months before the screening period; Severe visual or hearing impairment, unable to cooperate with the completion of the scale; A woman who is pregnant, or a woman of childbearing potential whose pregnancy test results are positive, or who is breastfeeding; or has a plan to have a child, unwilling or unable to take effective contraceptive measures within 30 days prior to the screening period or six months after the last use of the investigational drug. History of drug abuse or addiction; Three months prior to the randomization period or planned to use dual antiplatelet or anticoagulant drugs during the trial; Received any passive immunotherapy or other long-acting biologics used to prevent or delay cognitive decline within 1 year prior to screening; Investigators and relevant staff of the research Centre or others directly involved in programme implementation; The investigator considers that there are any circumstances that would cause the subject to be unable to complete the study or pose a significant risk to the subject or other factors that would interfere with the subject's ability to complete the study evaluation.

Sites / Locations

  • The First Affiliated Hospital Of USTCRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SHR-1707

SHR-1707 placebo

Arm Description

Up to4 cohorts of Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease patients will receive Multiple-ascending Dose of SHR-1707 injection

Up to 4 cohorts of Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease patients will receive Multiple-ascending Dose of SHR-1707 placebo injection

Outcomes

Primary Outcome Measures

To assess the number of patients with adverse events (AEs)
To assess the number of patients with clinically significant change from baseline in vital signs values,
To assess the number of patients with clinically significant change in physical examination,
To assess the number of patients with clinically significant change from baseline in laboratory examination,
To assess the number of patients with clinically significant change from baseline in 12-ECG values,
To assess the number of patients with clinically significant change in brain MRI (cerebral edema, microbleeding, etc.)

Secondary Outcome Measures

To assess the change from baseline in Brain Amyloid Plaque Deposition as measured by Aβ PET
To assess the ADA
To assess the number of patients with adverse events (AEs),
To assess the number of patients with clinically significant change from baseline in vital signs values,
To assess the number of patients with clinically significant change in physical examination,
To assess the number of patients with clinically significant change from baseline in laboratory examination,
To assess the number of patients with clinically significant change from baseline in 12-ECG values,
To assess the number of patients with clinically significant change in Head brain MRI (cerebral edema, microbleeding, etc.),

Full Information

First Posted
January 4, 2023
Last Updated
May 5, 2023
Sponsor
Shanghai Hengrui Pharmaceutical Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05681819
Brief Title
Safety, Tolerability and Pharmacodynamics of SHR-1707 in Alzheimer's Disease Patients.
Official Title
A Phase Ib, Randomized, Double-blind, Placebo-controlled, Multiple-ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacodynamics of Intravenous Administration of SHR-1707 In Patients With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 17, 2023 (Actual)
Primary Completion Date
August 18, 2025 (Anticipated)
Study Completion Date
August 18, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shanghai Hengrui Pharmaceutical Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Evaluate the Safety, Tolerability and Pharmacodynamics of Intravenous Administration of SHR-1707 In Patients with Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
SHR-1707 injection compared with placebo
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
41 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SHR-1707
Arm Type
Experimental
Arm Description
Up to4 cohorts of Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease patients will receive Multiple-ascending Dose of SHR-1707 injection
Arm Title
SHR-1707 placebo
Arm Type
Placebo Comparator
Arm Description
Up to 4 cohorts of Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease patients will receive Multiple-ascending Dose of SHR-1707 placebo injection
Intervention Type
Drug
Intervention Name(s)
SHR-1707
Intervention Description
Multiple-ascending Dose
Intervention Type
Drug
Intervention Name(s)
SHR-1707 placebo
Intervention Description
Multiple-ascending Dose
Primary Outcome Measure Information:
Title
To assess the number of patients with adverse events (AEs)
Time Frame
week 26
Title
To assess the number of patients with clinically significant change from baseline in vital signs values,
Time Frame
week 26
Title
To assess the number of patients with clinically significant change in physical examination,
Time Frame
week 26
Title
To assess the number of patients with clinically significant change from baseline in laboratory examination,
Time Frame
week 26
Title
To assess the number of patients with clinically significant change from baseline in 12-ECG values,
Time Frame
week 26
Title
To assess the number of patients with clinically significant change in brain MRI (cerebral edema, microbleeding, etc.)
Time Frame
week 26
Secondary Outcome Measure Information:
Title
To assess the change from baseline in Brain Amyloid Plaque Deposition as measured by Aβ PET
Time Frame
week26/52/78
Title
To assess the ADA
Time Frame
week26
Title
To assess the number of patients with adverse events (AEs),
Time Frame
week 52\week78
Title
To assess the number of patients with clinically significant change from baseline in vital signs values,
Time Frame
week 52\week78
Title
To assess the number of patients with clinically significant change in physical examination,
Time Frame
week 52\week78
Title
To assess the number of patients with clinically significant change from baseline in laboratory examination,
Time Frame
week 52\week78
Title
To assess the number of patients with clinically significant change from baseline in 12-ECG values,
Time Frame
week 52\week78
Title
To assess the number of patients with clinically significant change in Head brain MRI (cerebral edema, microbleeding, etc.),
Time Frame
week 52\week78

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥55and ≤85 on the date of signing the informed consent, males or females; BMI≥19kg/m2 and ≤32 kg/m2, weight ≥45 kg且≤100 kg at screening or baseline; must meet the diagnostic criteria for MCI due to AD or mild AD; The total score of HAMD-17 should be ≤10 scores at screening and baseline; The score of Hachinski ischemic scale should be ≤4 scores at screening and baseline; Qualitative amyloid PET scan results from the central laboratory confirmed the presence of pathological changes in AD; Agreed to test ApoE genotype; Have a stable caregiver; where symptomatic drugs for AD is used, they must be stable for at least 3 months prior to the baseline visit; Exclusion Criteria: Cognitive impairment of subjects due to other medical or neurological factors (other than AD); History of stroke or transient ischemic attack, seizures, or other unexplained loss of consciousness within the past year; Any psychiatric diagnosis that may interfere with the subject's cognitive assessment; Cannot tolerate MRI or has contraindications to MRI, has significant lesions shown on MRI during screening, or has other conditions that the investigator believes may bring a significant risk to the subject; Suspected allergy to Aβ antibody drugs and excipients. Patients who had severe trauma or had undergone surgery within 6 months prior to screening, or were scheduled to undergo surgery during the trial; History of moderate (3b) or severe renal failure or insufficiency; Uncontrolled hypertension: systolic blood pressure > 160mmHg and diastolic blood pressure >100mmHg in supine position during screening or baseline; 12-lead ECG showed QTcF >450ms for male and >470ms for female during screening; History of hypoglycemic coma or uncontrolled diabetes 6 months prior to the screening period; Thyroid dysfunction; Had unstable or clinically significant cardiovascular disease within 1 year prior to the screening period, had or currently has atrial fibrillation; History of malignancy within 5 years prior to screening; Patients with clinically significant systemic immunosuppression due to the persistent effects of immunosuppressive drugs; Human immunodeficiency virus antibody (HIV-Ab), treponema pallidum antibody and hepatitis C virus antibody (HCV-Ab) were positive during screening.Hepatitis B active subjects [Hepatitis B virus surface antigen (HBsAg) positive with HBV DNA > upper limit of normal] Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times ULN, or total bilirubin exceeding 2 times ULN Folic acid or vitamin B12 below the lower limit of normal coagulation disorders According to the investigators, the subjects were suicidal or had committed suicidal behavior in the six months before the screening period; Severe visual or hearing impairment, unable to cooperate with the completion of the scale; A woman who is pregnant, or a woman of childbearing potential whose pregnancy test results are positive, or who is breastfeeding; or has a plan to have a child, unwilling or unable to take effective contraceptive measures within 30 days prior to the screening period or six months after the last use of the investigational drug. History of drug abuse or addiction; Three months prior to the randomization period or planned to use dual antiplatelet or anticoagulant drugs during the trial; Received any passive immunotherapy or other long-acting biologics used to prevent or delay cognitive decline within 1 year prior to screening; Investigators and relevant staff of the research Centre or others directly involved in programme implementation; The investigator considers that there are any circumstances that would cause the subject to be unable to complete the study or pose a significant risk to the subject or other factors that would interfere with the subject's ability to complete the study evaluation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Miaomiao Shi
Phone
+8618036617171
Email
miaomiao.shi@hengrui.com
First Name & Middle Initial & Last Name or Official Title & Degree
Hongyan Qiu
Phone
+86 18817821303
Email
hongyan.qiu@hengrui.com
Facility Information:
Facility Name
The First Affiliated Hospital Of USTC
City
Hefei
State/Province
Anhui
ZIP/Postal Code
230001
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jiong Shi

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Safety, Tolerability and Pharmacodynamics of SHR-1707 in Alzheimer's Disease Patients.

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