Safety, Tolerability and Pharmacodynamics of SHR-1707 in Alzheimer's Disease Patients.
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SHR-1707 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 |
Drug: SHR-1707
Multiple-ascending Dose
|
| Placebo Comparator: SHR-1707 placebo 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 |
Drug: SHR-1707 placebo
Multiple-ascending Dose
|
Outcome Measures
Primary Outcome Measures
- To assess the number of patients with adverse events (AEs) [week 26]
- To assess the number of patients with clinically significant change from baseline in vital signs values, [week 26]
- To assess the number of patients with clinically significant change in physical examination, [week 26]
- To assess the number of patients with clinically significant change from baseline in laboratory examination, [week 26]
- To assess the number of patients with clinically significant change from baseline in 12-ECG values, [week 26]
- To assess the number of patients with clinically significant change in brain MRI (cerebral edema, microbleeding, etc.) [week 26]
Secondary Outcome Measures
- To assess the change from baseline in Brain Amyloid Plaque Deposition as measured by Aβ PET [week26/52/78]
- To assess the ADA [week26]
- To assess the number of patients with adverse events (AEs), [week 52\week78]
- To assess the number of patients with clinically significant change from baseline in vital signs values, [week 52\week78]
- To assess the number of patients with clinically significant change in physical examination, [week 52\week78]
- To assess the number of patients with clinically significant change from baseline in laboratory examination, [week 52\week78]
- To assess the number of patients with clinically significant change from baseline in 12-ECG values, [week 52\week78]
- To assess the number of patients with clinically significant change in Head brain MRI (cerebral edema, microbleeding, etc.), [week 52\week78]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥55and ≤85 on the date of signing the informed consent, males or females;
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BMI≥19kg/m2 and ≤32 kg/m2, weight ≥45 kg且≤100 kg at screening or baseline；
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must meet the diagnostic criteria for MCI due to AD or mild AD;
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The total score of HAMD-17 should be ≤10 scores at screening and baseline;
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The score of Hachinski ischemic scale should be ≤4 scores at screening and baseline;
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Qualitative amyloid PET scan results from the central laboratory confirmed the presence of pathological changes in AD;
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Agreed to test ApoE genotype;
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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:
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Cognitive impairment of subjects due to other medical or neurological factors (other than AD);
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History of stroke or transient ischemic attack, seizures, or other unexplained loss of consciousness within the past year;
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Any psychiatric diagnosis that may interfere with the subject's cognitive assessment;
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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;
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Suspected allergy to Aβ antibody drugs and excipients.
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Patients who had severe trauma or had undergone surgery within 6 months prior to screening, or were scheduled to undergo surgery during the trial;
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History of moderate (3b) or severe renal failure or insufficiency;
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Uncontrolled hypertension: systolic blood pressure > 160mmHg and diastolic blood pressure >100mmHg in supine position during screening or baseline;
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12-lead ECG showed QTcF >450ms for male and >470ms for female during screening;
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History of hypoglycemic coma or uncontrolled diabetes 6 months prior to the screening period;
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Thyroid dysfunction；
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Had unstable or clinically significant cardiovascular disease within 1 year prior to the screening period, had or currently has atrial fibrillation;
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History of malignancy within 5 years prior to screening;
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Patients with clinically significant systemic immunosuppression due to the persistent effects of immunosuppressive drugs;
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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]
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Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times ULN, or total bilirubin exceeding 2 times ULN
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Folic acid or vitamin B12 below the lower limit of normal
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coagulation disorders
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According to the investigators, the subjects were suicidal or had committed suicidal behavior in the six months before the screening period;
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Severe visual or hearing impairment, unable to cooperate with the completion of the scale;
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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.
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History of drug abuse or addiction;
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Three months prior to the randomization period or planned to use dual antiplatelet or anticoagulant drugs during the trial;
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Received any passive immunotherapy or other long-acting biologics used to prevent or delay cognitive decline within 1 year prior to screening;
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Investigators and relevant staff of the research Centre or others directly involved in programme implementation;
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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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Shanghai Hengrui Pharmaceutical Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SHR-1707-102