A Study of SHR-1707 With Mild Cognitive Impairment Due to Alzheimer's Disease or Mild Alzheimer's Disease

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

This study aims 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.

Inclusion Criteria:

1. Age ≥ 55 and ≤ 85 on the date of signing the informed consent, males or females;
2. BMI ≥ 19 kg/m2 and ≤ 32 kg/m2, weight ≥ 45 kg and ≤ 100 kg at screening or baseline;
3. Must meet the diagnostic criteria for MCI due to AD or mild AD;
4. The total score of HAMD-17 should be ≤ 10 scores at screening and baseline;
5. The score of Hachinski ischemic scale should be ≤ 4 scores at screening and baseline;
6. Qualitative amyloid PET scan results from the central laboratory confirmed the presence of pathological changes in AD;
7. Agreed to test ApoE genotype;
8. 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:

1. Cognitive impairment of subjects due to other medical or neurological factors (other than AD);
2. History of stroke or transient ischemic attack, seizures, or other unexplained loss of consciousness within the past year;
3. Any psychiatric diagnosis that may interfere with the subject's cognitive assessment;
4. 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;
5. Suspected allergy to Aβ antibody drugs and excipients;
6. Patients who had severe trauma or had undergone surgery within 6 months prior to screening, or were scheduled to undergo surgery during the trial;
7. History of moderate (3b) or severe renal failure or insufficiency;
8. Uncontrolled hypertension: systolic blood pressure > 160 mmHg and diastolic blood pressure >100 mmHg in supine position during screening or baseline;
9. 12-lead ECG showed QTcF > 450ms for male and > 470ms for female during screening;
10. History of hypoglycemic coma or uncontrolled diabetes 6 months prior to the screening period;
11. Thyroid dysfunction;
12. Had unstable or clinically significant cardiovascular disease within 1 year prior to the screening period, had or currently has atrial fibrillation;
13. History of malignancy within 5 years prior to screening;
14. Patients with clinically significant systemic immunosuppression due to the persistent effects of immunosuppressive drugs;
15. 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);
16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) exceeding 3 times ULN, or total bilirubin exceeding 2 times ULN;
17. Folic acid or vitamin B12 below the lower limit of normal;
18. coagulation disorders;
19. According to the investigators, the subjects were suicidal or had committed suicidal behavior in the six months before the screening period;
20. Severe visual or hearing impairment, unable to cooperate with the completion of the scale;
21. 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;
22. History of drug abuse or addiction;
23. Three months prior to the randomization period or planned to use dual antiplatelet or anticoagulant drugs during the trial;
24. Received any passive immunotherapy or other long-acting biologics used to prevent or delay cognitive decline within 1 year prior to screening;
25. Investigators and relevant staff of the research Centre or others directly involved in programme implementation;
26. 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.