Clinical trial NCT05681819: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Alzheimer's Disease
Lead sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-01-12
Enrollment: 33
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: SHR-1707 injection compared with placebo
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥55and ≤85 on the date of signing the informed consent, males or females;
2. BMI≥19kg/m2 and ≤32 kg/m2, weight ≥45 kg且≤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 \> 160mmHg and diastolic blood pressure \>100mmHg 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.

Primary outcomes:
measure: To assess the number of patients with adverse events (AEs)
timeFrame: week 26
measure: To assess the number of patients with clinically significant change from baseline in vital signs values,
timeFrame: week 26
measure: To assess the number of patients with clinically significant change in physical examination,
timeFrame: week 26
measure: To assess the number of patients with clinically significant change from baseline in laboratory examination,
timeFrame: week 26
measure: To assess the number of patients with clinically significant change from baseline in 12-ECG values,
timeFrame: week 26
measure: To assess the number of patients with clinically significant change in brain MRI (cerebral edema, microbleeding, etc.)
timeFrame: week 26
Secondary outcomes:
measure: To assess the change from baseline in Brain Amyloid Plaque Deposition as measured by Aβ PET
timeFrame: week26/52/78
measure: To assess the ADA
timeFrame: week26
measure: To assess the number of patients with adverse events (AEs),
timeFrame: week 52\week78
measure: To assess the number of patients with clinically significant change from baseline in vital signs values,
timeFrame: week 52\week78
measure: To assess the number of patients with clinically significant change in physical examination,
timeFrame: week 52\week78
measure: To assess the number of patients with clinically significant change from baseline in laboratory examination,
timeFrame: week 52\week78
measure: To assess the number of patients with clinically significant change from baseline in 12-ECG values,
timeFrame: week 52\week78
measure: To assess the number of patients with clinically significant change in Head brain MRI (cerebral edema, microbleeding, etc.),
timeFrame: week 52\week78
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital Of USTC
state: Anhui
Study officials:
References: