Silkworm Pupa Powder Improves Alzheimer's Disease

Prior treatment

• Administration of any new chemical entity in an AD clinical study within 6 months prior to screening.
• Participation in a clinical study involving therapeutic monoclonal antibodies, antibody-derived proteins, immunoglobulin therapy, or vaccines within 6 months prior to screening.
• Participation in a clinical study involving any anti-amyloid therapies (including any monoclonal antibody therapy and any BACE inhibitor therapy).
• Any inadequately controlled immune disorder, or immune disease requiring treatment with immunoglobulins, systemic monoclonal antibodies (or derivatives), systemic immunosuppressants, or plasmapheresis during the study.
• Participation in another concurrent silkworm pupa powder intervention study conducted at the same study center.

Other illness

• Diagnosis of dementia other than Alzheimer's disease (AD) or other central nervous system disorders.
• Unstable vital signs accompanied by abnormalities in cardiac, pulmonary, hepatic, renal, or other organ functions.
• Abnormally low folate and/or vitamin B12 levels, or evidence that hypothyroidism has caused or exacerbated the participant's dementia. Abnormal syphilis test results.
• Comorbid psychiatric disorders.
• Intolerance or allergy to the study medication (silkworm pupa powder).
• Diagnosis of clinically significant cardiovascular or cerebrovascular disease requiring treatment within 12 months or at present.
• Any other inadequately controlled condition (e.g., cardiac, respiratory, renal, or gastrointestinal disorders affecting absorption, such as gastric cancer, gastric bypass surgery, or recurrent diarrhea) that may jeopardize participant safety or interfere with study assessments, as judged by the investigator.

Lab values

• Clinically significant abnormalities in physical examination, vital signs, laboratory tests, or electrocardiogram (ECG) requiring further investigation, treatment, or posing risks to study procedures or safety.
• Inadequately controlled bleeding disorders (including platelet count \<50,000 or INR \>1.5 for participants not on anticoagulants, e.g., warfarin). Participants on anticoagulants must have their anticoagulation status optimized and receive a stable dose within 4 weeks prior to screening. Participants receiving anticoagulant therapy must not participate in cerebrospinal fluid (CSF) assessments.

Other

• Long-term alcoholism or substance abuse that may compromise the evaluation of treatment efficacy.
• Abnormalities detected on cranial MRI, including ischemic or hemorrhagic infarctions, hydrocephalus, or brain tumors.
• Geriatric Depression Scale-15 (GDS-15) score \>4 at screening.

• Diagnosis of probable Alzheimer's disease (AD) according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. Disease severity is classified as mild to moderate, defined as a Mini-Mental State Examination (MMSE) total score of 0-24 points, inclusive, at both screening and baseline.
• Confirmation of AD pathology per the 2024 revised AD diagnostic criteria (biomarker-defined AD with both Aβ and tau positivity):
• Aβ positivity: Plasma Aβ42/40 ratio ≤0.08 or amyloid-PET positivity (SUVR ≥1.1).
• Tau positivity: Plasma p-tau217 ≥2.5 pg/mL (or CSF p-tau181/Aβ42 ratio ≥0.02).
• Age 50 to 90 years (inclusive), male or female, with at least a primary school education.
• Stable medication use: If receiving approved AD therapies (e.g., acetylcholinesterase inhibitors, GV-971, NMDA receptor antagonists), doses must remain stable for ≥12 weeks prior to baseline. Treatment-naïve participants are also eligible. All other permitted non-AD related concomitant medications must remain stable for ≥4 weeks prior to baseline unless otherwise specified.
• Hachinski Ischemia Scale (HIS) total score ≤4.
• Geriatric Depression Scale-15 (GDS-15) total score ≤4.
• Neuroimaging evidence: Screening CT/MRI showing age-related brain changes or cerebral atrophy.
• Participant has a stable and reliable caregiver, as confirmed by the investigator.
• Written informed consent must be provided by the participant or, if the participant lacks decision-making capacity, by a legally authorized representative (in accordance with local laws, regulations, and customs). Participants must agree to provide peripheral blood, stool, and urine samples during the study for biomarker analysis.