This is a multicenter, randomized, double-blind, placebo-controlled parallel Phase II core period study to evaluate the efficacy and safety of TTYP01 Tablets in early symptomatic AD (Mild cognitive impairment \[MCI\] due to AD, or mild AD dementia).
A total of 180 participants will be randomized into 3 parallel groups: 2 TTYP01 dose groups and 1 placebo group.
Age between 60 and 85 years (inclusive, based on the date of signing the informed consent), applicable to all genders.
Must meet the 2024 Alzheimer's Association (AA) Workgroup revised criteria for diagnosing MCI due to AD or mild AD dementia.
CDR score: At screening and baseline, the CDR global score must be 0.5 or 1.0, and the CDR memory score must be 0.5 or higher.
MMSE score: At screening, the MMSE score must be 22 or higher.
History of intracranial infection or traumatic brain injury.
Severe coronary heart disease, cardiac insufficiency (New York Heart Association Class Ⅲ and Class IV), atrial fibrillation, and other heart diseases within six months prior to signing ICF.
History of cancer within the last 3 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, nonprogressive prostate cancer, or other cancers with a low risk of recurrence or spread.
Intracranial space occupying lesions or brain tumors will be excluded unless, based on the opinion of the investigators and medical monitors, the medical condition will not interfere with cognitive assessments and safety.
Parallel
TTYP01 tables 60mg
Drug2 TTYP01 30 mg tablets + 1 placebo tablet BID
TTYP01 tables 90mg
Drug(3 TTYP01 30 mg tablets
TTYP01 tables 0mg
Drug3 placebo tablets
Change from baseline in the Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB) score at Week 78.
Number of participants with Adverse events, serious adverse events, adverse events of special interest
TTYP01 PK parameter (AUC (0-t,0-24,∞)
Change From Baseline in Amyloid Positron Emission Tomography (PET) Using Centiloids at Week 39 and Week 78
Change from baseline in blood p-tau 217 at week 78.
Changes from baseline in Mini-Mental State Examination (MMSE).
To explore the exposure-clinical effect relationship of TTYP01 Tablets in treating early symptomatic AD.
Correlation analyses between edaravone exposure in blood and changes of CDR-SB, ADCOMS, ADAS-Cog13, ADCS-ADL, and MMSE score at Week 78.
To explore the exposure-effect relationship of TTYP01 Tablets on cerebral amyloid plaque deposition, and MRI brain volume.
Correlation analyses between edaravone exposure in blood and changes of Aβ-PET and MRI brain volume at Week 39 and Week 78.
To assess the effect of TTYP01 vs. placebo on clinical progression, behavioral, neuropsychiatric symptom and study partner burden in early symptomatic AD patients.
The proportion of clinical progression or clinical improvement in the test group compared with the placebo group at Week 13, 26, 39, 52, 65, and 78. ①Progression criteria: 1. Any increase in the overall Clinical Dementia Rating Scale (CDR) score from baseline; 2. CDR-SB is higher than baseline. Criteria 1 and 2 are evaluated separately. ②Improvement criteria: 1. Any decrease in the overall CDR score from baseline; 2. CDR-SB is lower than baseline. Criteria 1 and 2 are evaluated separately. Time to clinical progression (criteria 1: time to increase in overall CDR score from baseline; 2: time to increase in CDR-SB from baseline). Changes in Neuropsychiatric Inventory (NPI) scores from baseline at Week 26, 52 and 78. Changes from baseline in the Zarit Burden Interview (ZBI) at Week 26, 52, and 78.
To evaluate the effects of TTYP01 Tablets on blood PD markers (AD biomarkers and cytokines).
Changes from baseline in levels of AD biomarkers amyloid-beta peptides (Aβ42/40), Glial Fibrillary Acidic Protein (GFAP), and neurofilament light chain (NfL) at Week 4, 8, 13, 39 and 78. Changes in cytokines: interferon-gamma (IFN-γ), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) at Week 4, 8, 13, 39 and 78
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