中国临床试验注册中心 - 世界卫生组织国际临床试验注册平台一级注册机构

注册号： Registration number：	ChiCTR2500113851
最近更新日期： Date of Last Refreshed on：	2025-12-03 18:00:11
注册时间： Date of Registration：	2025-12-03 00:00:00
注册号状态：	预注册
Registration Status：	Prospective registration
注册题目：	一项为期72周的在早期阿尔茨海默病受试者中评估VHB937的疗效和安全性的随机、安慰剂对照、平行组研究，随后进入扩展期
Public title：	A randomized, placebo-controlled, parallel group, 72-week study to evaluate the efficacy and safety of VHB937 in participants with early Alzheimer’s Disease followed by an Extension
注册题目简写：	一项在早期阿尔茨海默病受试者中评估VHB937的疗效和安全性的随机、安慰剂对照研究，随后进入扩展期
English Acronym：	A randomized, placebo-controlled, parallel group, 72-week study to evaluate the efficacy and safety of VHB937 in participants with early Alzheimer’s Disease followed by an Extension
研究课题的正式科学名称：	一项为期72周的在早期阿尔茨海默病受试者中评估VHB937的疗效和安全性的随机、安慰剂对照、平行组研究，随后进入扩展期
Scientific title：	A randomized, placebo-controlled, parallel group, 72-week study to evaluate the efficacy and safety of VHB937 in participants with early Alzheimer’s Disease followed by an Extension
研究课题代号(代码)： Study subject ID：
在二级注册机构或其它机构的注册号： The registration number of the Partner Registry or other register：

申请注册联系人：	郁金泰	研究负责人：	郁金泰
Applicant：	Jintai Yu	Study leader：	Jintai Yu
申请注册联系人电话： Applicant telephone：	+86 186 7899 9982	研究负责人电话： Study leader's telephone：	+86 186 7899 9982
申请注册联系人传真： Applicant Fax：		研究负责人传真： Study leader's fax：
申请注册联系人电子邮件： Applicant E-mail：	yujintai@163.com	研究负责人电子邮件： Study leader's E-mail：	jintai_yu@fudan.edu.cn
申请单位网址(自愿提供)： Applicant website(voluntary supply)：		研究负责人网址(自愿提供)： Study leader's website(voluntary supply)：
申请注册联系人通讯地址：	上海市闵行区金光路958号	研究负责人通讯地址：	乌鲁木齐中路12号
Applicant address：	No 958 Jinguang Road, Minhang District, Shanghai	Study leader's address：	No.12 Middle Wulumuqi Road,Shanghai
申请注册联系人邮政编码： Applicant postcode：		研究负责人邮政编码： Study leader's postcode：
申请人所在单位：	复旦大学附属华山医院
Applicant's institution：	Huashan Hospital, Fudan University
研究负责人所在单位：	复旦大学附属华山医院
Affiliation of the Leader：	Huashan Hospital, Fudan University

是否获伦理委员会批准：	是
Approved by ethic committee：	Yes
伦理委员会批件文号： Approved No. of ethic committee：	(2025)临审第(938)号	伦理委员会批件附件： Approved file of Ethical Committee：	查看附件View
批准本研究的伦理委员会名称：	复旦大学附属华山医院伦理审查委员会
Name of the ethic committee：	Institutional Review Board Huashan Hospital Fudan University
伦理委员会批准日期： Date of approved by ethic committee：	2025-08-12 00:00:00
伦理委员会联系人：	全菁
Contact Name of the ethic committee：	Quan Jing
伦理委员会联系地址：	乌鲁木齐中路12号
Contact Address of the ethic committee：	No.12 Middle Wulumuqi Road,Shanghai
伦理委员会联系人电话： Contact phone of the ethic committee：	+86 21 5288 8921	伦理委员会联系人邮箱： Contact email of the ethic committee：	quanjing1975@163.com

研究实施负责（组长）单位：

复旦大学附属华山医院

Primary sponsor：

Huashan Hospital, Fudan University

研究实施负责（组长）单位地址：

乌鲁木齐中路12号

Primary sponsor's address：

No.12 Middle Wulumuqi Road,Shanghai

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	复旦大学附属华山医院	具体地址：	乌鲁木齐中路12号
Institution hospital：	Huashan Hospital, Fudan University	Address：	No.12 Middle Wulumuqi Road,Shanghai

经费或物资来源：

NA

Source(s) of funding：

Novartis Pharma AG

研究疾病：

早期阿尔茨海默病

Target disease：

Early Alzheimer's disease

研究疾病代码：

Target disease code：

研究类型：

干预性研究

Study type：

Interventional study

研究所处阶段：

II期临床试验

Study phase：

2

研究设计：

随机平行对照

Study design：

Parallel

研究目的：

在阿尔茨海默病（AD）中，尽管存在AD病理学改变，但VHB937有望激活小胶质细胞，该细胞在保护脑功能方面可发挥作用。这项为期72周、随机、双盲、安慰剂对照、平行组研究的目的是在早期AD受试者中评估VHB937 10 mg/kg和30 mg/kg每4周输注一次与安慰剂相比的安全性和疗效。

Objectives of Study：

In Alzheimer's disease (AD), VHB937 is expected to activate microglia that play a role in preservation of brain function despite AD pathology.

The purpose of this 72-week, randomized, double-blind, placebo-controlled, parallel group study is to evaluate the safety and efficacy of VHB937 10 mg/kg and 30 mg/kg administered as infusion every 4 weeks, as compared to placebo in participants with early AD.

药物成份或治疗方案详述：

Description for medicine or protocol of treatment in detail：

纳入标准：

Inclusion criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Male and female participants 50 to 85 years of age, with a maximum body weight of 180kg at the time of signing the informed consent.
3. Diagnosis of Mild Cognitive Impairment (MCI) due to AD or mild AD according to theNational Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria(Jack et al 2018) at Screening.
4. Clinical Dementia Rating (CDR) Global score of 0.5 or 1.0 at Screening and Baseline.
5. ADAS-Cog14 total score between 13 and 54 (inclusive) at Screening.
6. Biomarker-based confirmation of Alzheimer disease (AD) at Screening based on cerebra lspinal fluid (CSF) biomarkers or amyloid PET imaging. Historical confirmation of amyloid positivity by CSF or PET is accepted.
7. Fluency in local language in which study assessments are administered and evidence of adequate pre-morbid intellectual functioning and adequate visual and auditory abilities to perform all aspects of the cognitive and functional assessments;
8. Reliable study partner such as spouse, sibling, close friend, or caregiver who can accompany the participant at study visits in which informant scales are administered. The study partner should be fluent in and able to read the local language in which study assessments are administered and also willing and able to provide information to study Investigator/staff. The study partner must, in the opinion of the Investigator, spend sufficient time with the participant on a regular basis such that this person can reliably fulfill the study requirements. There should be no foreseeable plan for the study partner to change during the Double-blind period.
9. Participants receiving an acetylcholinesterase inhibitor (AChEI) or memantine or both for AD must be on a stable dose for at least 12 weeks prior to Randomization. For participants who discontinued these medications before Screening, the stop date should be at least 12 weeks before Randomization. Treatment-naïve participants can also be enrolled into the study.

排除标准：

1 患有由AD以外的疾病引起的痴呆，包括但不限于额颞叶痴呆（FTD）、帕金森病痴呆、路易体痴呆、亨廷顿病性痴呆、血管性痴呆。
2.存在APOE4纯合子状态。只有在获得数据安全监查委员会的积极建议后，才允许入组APOE4纯合子状态的受试者。
3.既往或当前接受抗淀粉样蛋白抗体治疗。
4.随机分组前12个月内发生过短暂性脑缺血发作（TIA）或卒中。
5. 患有可能影响认知功能或完成研究能力的影响中枢神经系统的其他重大神经系统疾病（痴呆除外），包括但不限于严重脑部感染、外伤性脑损伤、多次脑震荡、癫痫或复发性癫痫发作（儿童期发热性癫痫发作除外）。
6. 当前初步诊断为存在精神疾病或症状，研究者认为可能对药物作用解读产生混杂影响、影响认知功能评估或影响受试者完成研究的能力。研究者评估认为当前重度抑郁发作未得到充分控制的受试者以及有精神分裂症和其他慢性精神病史的受试者均排除在外。
7. 已知或疑似在筛选前2年内有药物或酒精滥用或依赖史，或筛选时尿液药物检测呈阳性。如果根据研究者的临床意见，尿液药物检测中苯二氮卓类或阿片类药物检测呈阳性的受试者是由于既往／伴随使用含苯二氮卓类或阿片类药物治疗医学病症，而不是由于药物滥用，则不需要排除这些受试者。
8. 如果受试者对哥伦比亚自杀严重程度评定量表（C-SSRS）自杀想法第4项或第5项的自杀倾向评估回答为“是”（如果在过去6个月内出现过这种想法）或对自杀行为部分的任何一项回答为“是”（如果在筛选前2年内发生过这种行为），则需要排除；如果受试者在基线时对自杀想法第4项或第5项的回答为“是”且对自杀行为的任何一项回答为“是”，也需要排除。
9. 筛选时中心实验室检查结果显示血清维生素B12水平异常偏低（如果受试者正在接受维生素B12注射液，则该水平应≥正常值下限）。
10. 存在未控制的甲状腺疾病或未控制的糖尿病，或筛选时中心实验室结果显示甲状腺功能或空腹血糖存在有临床意义的实验室检查异常（经研究者评估）。研究者应确保糖尿病受试者的血糖在研究期间得到充分控制。
11. 筛选时中心实验室检查结果显示活动性乙型肝炎病毒（HBV）（乙型肝炎表面抗原和总抗HB核心抗体阳性）、活动性丙型肝炎病毒（HCV）（HCV-RNA阳性）、人类免疫缺陷病毒（HIV）阳性（HIV抗原或抗体阳性）或在筛选访视前4周内存在具有临床意义的全身性病毒、细菌或真菌感染的体征／症状（对于这种情况，消退后可对受试者进行重新筛选）。对于日本受试者，除上述标准外，根据日本肝病学会指南（2020年日本肝病学会肝炎管理指南起草委员会），在无HBV疫苗接种史的情况下，如果HBsAg和HBcAb检测结果均为阴性，则必须排除筛选时乙型肝炎表面抗体（HBsAb）检测结果为阳性的受试者。
12. 有肝病或肝损伤（上述肝炎除外）的临床证据，定义为筛选时中心实验室检查显示以下任一结果： •总胆红素>1.5×ULN， •碱性磷酸酶（AP）>3×ULN， •AST（SGOT）或ALT（SGPT）>3×ULN，以及 •γ-谷氨酰转移酶（GGT）>3×ULN。
13.患有未得到充分控制或在研究期间需要生物制剂治疗的任何免疫性疾病。
14.有心血管疾病史或当前诊断为心血管疾病，表明受试者参加研究会有显著的安全性风险，包括但不限于： •心肌梗死或不稳定型心绞痛（筛选前6个月内）或有临床意义且需要治疗的心律失常（例如，持续性室性心动过速）以及有临床意义的二度或三度房室传导阻滞（未植入起搏器）。 •有家族性长QT综合征或已知的尖端扭转型室性心动过速家族史。 •筛选时静息QTcF≥450 ms（男性）或≥460 ms（女性）或无法确定QTcF间期。
15.筛选时中心实验室检查结果显示重度肾功能损害（肾小球滤过率<30 mL/min/1.73 m2）。
16.筛选前3年内患有活动性恶性肿瘤（已接受根治性治疗的基底细胞癌或成功治疗的皮肤鳞状细胞癌、宫颈原位癌或子宫癌除外，例如：完全切除且边缘清晰）或研究者认为预期寿命小于24个月的受试者。
17.患有病情不稳定且未充分控制或可能影响受试者安全或干扰研究评估的任何其他医学病症（例如，心血管、呼吸、胃肠道、肾脏疾病）。存在研究者认为需要进一步检查或治疗或可能干扰受试者安全的任何其他具有临床意义的异常（生命体征、实验室检查或ECG）。
18.计划在研究期间进行需要全身、脊椎或硬脊膜外麻醉的手术。如果计划的手术仅需要局部麻醉，可作为日间手术进行且术后无需住院，并且研究者认为该手术不会干扰研究程序和受试者的安全，则无需排除。
19.基线时使用研究方案禁用药物（例如，全身性免疫抑制或免疫调节治疗）。
20.对单克隆抗体或研究药物辅料有超敏反应史。
21.在筛选前6个月内参与了涉及AD任何新化学实体（抗体除外）给药的临床研究；在筛选前1年内接受任何试验性抗体（抗淀粉样蛋白抗体除外）治疗AD，除非可以证明该受试者被随机分配至安慰剂组，否则应排除该受试者。
22.在筛选前6个月或5个半衰期（以时间较长者为准）内参与了涉及任何治疗性单克隆抗体、单克隆抗体衍生的蛋白、免疫球蛋白疗法或疫苗的临床研究，以及在筛选前30天内使用了任何其他试验性药物，除非可以证明该受试者被随机分配至安慰剂组，否则应排除该受试者。
23.目前入组了另一项涉及试验用药品的干预性临床试验。
24.存在以下可能妨碍受试者进行CSF采集的医学病症（仅适用于进行CSF采集的受试者）：既往／已知对局部麻醉剂过敏、任何背部手术史（单节段显微椎间盘切除术或椎板切除术除外）、脊柱畸形、腰椎穿刺部位当前存在皮肤感染和／或计划穿刺部位存在明显皮肤变化（例如，咖啡样痣、毛发痣、脂肪瘤），以及通过眼科检查发现颅内压升高的受试者。
25.存在MRI扫描禁忌症，包括存在心脏起搏器／除颤器、铁磁性金属植入物（例如，除已获准可安全用于MRI扫描仪的器械外，植入颅骨和心脏的器械）。
26.患有未得到充分控制（包括筛选时中心实验室检查结果显示血小板计数<50,000或国际标准化比值[INR]>1.5）的出血性疾病以及接受抗凝剂治疗的受试者。
27.筛选时脑部MRI上有显著病理学发现： •有可能提示痴呆其他潜在病因的其他显著异常的证据，或可能影响受试者安全参与研究的有临床意义的发现。 •有一处以上微出血（定义为最大直径≤10 mm）；既往单次出血最大直径>10 mm；有任何浅表铁质沉着区域；有血管源性水肿证据；有脑挫伤、脑软化、动脉瘤或感染性病变证据；有多发性（≥2处）腔隙性梗死（不考虑梗死部位）或卒中（累及主要血管区域）、重度小血管或白质疾病证据；占位性病变；或脑肿瘤（但是，不排除诊断为脑膜瘤或蛛网膜囊肿且最大直径<1 cm的病变）。
28.妊娠或哺乳期女性受试者。
29.具有生育能力的女性（定义为从月经初潮至绝经期间从生理角度能够妊娠的所有女性），除非她们在接受研究治疗期间以及停用研究药物后6个月内使用高效避孕方法（年失败率<1%）。如果女性已经自然（自发）闭经12个月且有相应的临床表现（例如，激素水平证实绝经和／或具有与年龄相符的血管舒缩症状史），则视为绝经后状态。高效避孕方法包括： • 完全禁欲（与受试者首选的日常生活方式一致）。请注意，定期禁欲（例如，日历法、排卵法、症状体温法、排卵后法）和体外射精不属于可接受的避孕方法。 • 在接受研究治疗前至少6周行双侧卵巢切除术（联合或不联合子宫切除术）、全子宫切除术或双侧输卵管切除术。如果只接受了卵巢切除术，仅当通过后续激素水平评估证实女性没有生育能力时，才认为其不具有生育能力。 • 在接受研究治疗前至少6周行双侧输卵管阻塞术、双侧输卵管结扎术。 • 筛选前至少6个月女性受试者的男性伴侣行绝育术（输精管切除术），前提是其伴侣经医学证实手术成功。 • 使用激素避孕方法： • 抑制排卵的复方激素避孕药（含雌激素和孕激素）；口服、阴道内或经皮给药。 • 仅含孕激素的激素避孕药（抑制排卵不是其主要或唯一的作用方式）：口服、注射或植入给药。 • 宫内避孕器（IUD）或宫内激素释放系统（IUS）如果使用激素避孕方法，女性应在开始研究治疗前至少3个月稳定使用同一方法。如果当地法规的要求比以上所列避孕方法严格，则应遵循当地法规，并将在知情同意书（ICF）中进行描述。

Exclusion criteria：

1. Dementia due to a condition other than AD including, but not limited to, frontal temporal dementia (FTD), Parkinson's disease, dementia with Lewy bodies, Huntington disease, vascular dementia. 2. APOE4 HM status. Participants with APOE4 HM status will be allowed only after DMC safety review and following positive recommendation from data monitoring committee (DMC). 3. Prior or current treatment with an anti-amyloid antibody. 4. Transient ischemic attacks (TIA) or stroke occurring within 12 months prior to randomization. 5. Other significant neurological disease affecting the central nervous system other than dementia, that may affect cognition or ability to complete the study, including but not limited to, serious infection of the brain, traumatic brain injury, multiple concussions,epilepsy or recurrent seizures (except febrile childhood seizures). 6. Any current primary diagnosis of psychiatric disorder or symptom that in the judgment of the Investigator is likely to confound the interpretation of drug effect, affect cognitive assessment, or affect the participant capability to complete the study. Participants with a current major depressive episode that based on Investigator assessment is not adequately controlled and participants with history of schizophrenia and other chronic psychosis are excluded. 7. Known or suspected history of drug or alcohol abuse or dependence within 2 years before Screening or a positive urine drug test at Screening. Participants who test positive for benzodiazepines or opioids in urine drug testing do not need to be excluded if, in the clinical opinion of the Investigator, this is due to prior/concomitant medications containing benzodiazepines or opioids for a medical condition and not due to drug abuse. 8. Answer "Yes" to Suicidality assessment to Columbia Suicide Severity Rating Scale (CSSRS) Suicidal ideation items 4 or 5, if this ideation occurred in the past 6 months or "Yes" on any item of the Suicidal behavior section, if this behavior occurred in the past 2 years before Screening; answer "Yes" to Suicidal ideation items 4 or 5 and "Yes" on any item of the Suicidal behavior at Baseline will also be exclusionary. 9. Abnormally low serum vitamin B12 levels in central laboratory results at Screening (if participant is taking vitamin B12 injections level should be at or above the lower limit of normal). 10. Uncontrolled thyroid disease or uncontrolled diabetes or clinically significant laboratory abnormalities for thyroid function or fasting glucose in central laboratory results at Screening, as assessed by Investigator. The Investigator should ensure that the diabetic participants remain adequately controlled during the study. 11. Active hepatitis B virus (HBV) (hepatitis B surface antigen and total anti-HB core antibody positive), active hepatitis C virus (HCV) (HCV-RNA positive), human immunodeficiency virus positivity (HIV) (HIV antigen or antibody positive) in central laboratory results at Screening or signs/symptoms of a clinically significant systemic viral, bacterial, or fungal infection within 4 weeks prior to the Screening visit (for such cases, participants can be re-screened upon resolution). For Japanese participants, according to the guideline of Japan Society of Hepatology (Drafting Committee for Hepatitis Management Guidelines the Japan Society of Hepatology 2020), in addition to the above criteria: in the absence of a positive history of HBV vaccination, participants with positive hepatitis B surface antibody (HBsAb) test at screening must be excluded if the test for both HBsAg and HBcAb are negative. 12. Clinical evidence of liver disease or liver injury (other than hepatitis specified above) defined by any of the following results in central laboratory at Screening: • Total bilirubin > 1.5 x ULN, • Alkaline phosphatase (AP) > 3 x ULN, • AST (SGOT) or ALT (SGPT) > 3 x ULN, and • Gamma-glutamyl-transferase (GGT) > 3 x ULN. 13. Any immunological disease which is not adequately controlled, or which requires treatment with biologic drugs during the study. 14. History or current diagnosis of cardiovascular conditions indicating significant risk of safety for participants in the study such as, but not limited to: • Myocardial infarction or unstable angina (within 6 months of Screening) or clinically significant cardiac arrhythmia (e.g., sustained ventricular tachycardia) requiring treatment and clinically significant second- or third-degree AV block without a pacemaker. • Familial long QT syndrome or known family history of Torsade de Pointe. • Resting QTcF >= 450 ms (male) or >= 460 ms (female) at Screening or inability to determine the QTcF interval. 15. Severe renal impairment (Glomerular Filtration Rate < 30 mL/min/1.73 m2) in central laboratory results at Screening. 16. Active malignant neoplasms within 3 years before Screening (except for basal cell carcinoma or successfully treated squamous cell carcinoma of the skin, in situ carcinoma of cervix or the uterus that have been radically treated e.g., completely excised with clear margins) or participants that have a life expectancy of less than 24 months in the opinion of the Investigator. 17. Any other medical conditions (e.g., cardiovascular, respiratory, gastrointestinal, renal disease) which are not stable and adequately controlled or which could affect the participant’s safety or interfere with the study assessments. Any other clinically significant abnormalities (vital signs, laboratory tests or ECG) which in the opinion of the Investigator require further investigation or treatment or which may interfere with participant’s safety. 18. Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study. Planned surgery that requires only local anesthesia, and that can be undertaken as day case without inpatient stay postoperatively need not result in exclusion if in the opinion of the Investigator this operation will not interfere with study procedures and participant safety. 19. Taking medications prohibited by the protocol (e.g., systemic immunosuppressive or immunomodulatory therapy) at Baseline. 20. History of hypersensitivity to monoclonal antibodies or excipients of the study drug. 21. Participation in a clinical study involving dosing of any new chemical entities for AD (other than antibodies) within 6 months prior to Screening; any investigational antibodies for the treatment of AD within 1 year prior to Screening (other than anti-amyloid antibodies), unless it can be documented that the participant was randomized to placebo. 22. Participation in a clinical study involving any therapeutic monoclonal antibody, protein derived from a monoclonal antibody, immunoglobulin therapy, or vaccine within 6 months or 5 half-lives (whichever is longer) prior to Screening and use of any other investigational drugs within 30 days prior to Screening, unless it can be documented that the participant was randomized to placebo. 23. Currently enrolled in another interventional clinical trial involving an investigational product. 24. Medical conditions that would prevent the participant from undergoing CSF collection (applicable only for participants undergoing CSF collection): history of/ known allergy to local anesthetic, any history of back surgery (with the exception of microdiscectomy or laminectomy over 1 level), spinal deformities, current dermatological infection at the lumbar puncture spot and/or significant skin alterations at the planned puncture place (e.g., café-au-lait-naevi, haired naevi, lipoma), participants with elevated Intracranial Pressure detected by ophthalmological examination. 25. Contraindications to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in skull and cardiac devices other than those approved as safe for use in MRI scanners). 26. Bleeding disorder that is not under adequate control (including a platelet count <50,000 or international normalized ratio [INR] > 1.5 in central laboratory results at Screening) and participants receiving anticoagulants. 27. Significant pathological findings on brain MRI at Screening: • Evidence of other significant abnormalities that could indicate other potential etiologies for dementia or a clinically significant finding that may impact the participant’s ability to safely participate in the study. • More than one microhemorrhage (defined as 10 mm or less at the greatest diameter); a single prior hemorrhage greater than 10 mm at greatest diameter; any area of superficial siderosis; evidence of vasogenic edema; evidence of cerebral contusion, encephalomalacia, aneurysms, or infective lesions; evidence of multiple (>= 2) lacunar infarcts irrespective of location or stroke involving a major vascular territory, severe small vessel, or white matter disease; space occupying lesions; or brain tumors (however, lesions diagnosed as meningiomas or arachnoid cysts and less than 1 cm at their greatest diameter need not be exclusionary). 28. Pregnant or breast-feeding female participants. 29. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using highly effective methods of contraception (failure rate < 1% per year) while taking study treatment and for 6 months after stopping study treatment. Women are considered postmenopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or ageappropriate history of vasomotor symptoms). Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Note that periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. • Bilateral oophorectomy with or without hysterectomy, total hysterectomy or bilateral salpingectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment are they considered to be not of childbearing potential. • Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks before taking study treatment). • Sterilization (vasectomy) of male partner(s) of the female participant at least 6 months prior to screening provided partner(s) has(have) received medical confirmation of surgical success. • Use of hormonal contraception methods: • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; oral, intravaginal or transdermal. • Progestogen-only hormonal contraception (where inhibition of ovulation is not the primary or only mode of action): oral, injectable or implantable. • Intrauterine device (IUD) or intrauterine hormone-releasing system (IUS) In case of use of hormonal contraception, women should have been stable on the sam;

研究实施时间：

Study execute time：

从 From 2025-12-10 00:00:00至 To 2030-07-21 00:00:00

征募观察对象时间：

Recruiting time：

从 From 2025-12-10 00:00:00 至 To 2029-12-31 00:00:00

干预措施：

Interventions：

组别：	VHB937 10 mg/kg	样本量：	62
Group：	VHB937 10 mg/kg	Sample size：	62
干预措施：	VHB937	干预措施代码：
Intervention：	VHB937	Intervention code：

组别：	VHB937 30 mg/kg	样本量：	220
Group：	VHB937 30 mg/kg	Sample size：	220
干预措施：	VHB937	干预措施代码：
Intervention：	VHB937	Intervention code：

组别：	安慰剂	样本量：	125
Group：	placebo	Sample size：	125
干预措施：	NA	干预措施代码：
Intervention：	NA	Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：	中国	省(直辖市)：	上海市	市(区县)：
Country：	China	Province：	Shanghai	City：
单位(医院)：	复旦大学附属华山医院	单位级别：	三级甲等
Institution hospital：	Huashan Hospital, Fudan University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属邵逸夫医院	单位级别：	三级甲等
Institution hospital：	Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	吉林省	市(区县)：
Country：	China	Province：	Jilin	City：
单位(医院)：	吉林大学第一医院	单位级别：	三级甲等
Institution hospital：	The First Hospital of Jilin University	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	浙江省	市(区县)：
Country：	China	Province：	Zhejiang	City：
单位(医院)：	浙江大学医学院附属第二医院	单位级别：	三级甲等
Institution hospital：	The second affiliated hospital of Zhejiang University school of medicine	Level of the institution：	Tertiary A

国家：	中国	省(直辖市)：	天津市	市(区县)：
Country：	China	Province：	Tianjin	City：
单位(医院)：	天津市环湖医院	单位级别：	三级甲等
Institution hospital：	Tianjin Huanhu Hospital	Level of the institution：	Tertiary A

测量指标：

Outcomes：

指标中文名：	主要指标：评估VHB937与安慰剂相比对认知和功能的影响	指标类型：	主要指标
Outcome：	Primary objectives: To evaluate the effect of VHB937 compared to placebo on cognition and function	Type：	Primary indicator
测量时间点：	临床痴呆评定量表-总评分（CDR-SB）从基线至第72周的变化	测量方法：	临床痴呆评定量表-总评分（CDR-SB)
Measure time point of outcome：	Change from Baseline to Week 72 in the Clinical Dementia Rating scale – Sum of Boxes (CDR-SB)	Measure method：	Clinical Dementia Rating scale – Sum of Boxes (CDR-SB)

指标中文名：	不良事件	指标类型：	次要指标
Outcome：	Adverse event	Type：	Secondary indicator
测量时间点：		测量方法：
Measure time point of outcome：		Measure method：

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：	全血	组织：
Sample Name：	whole blood	Tissue：
人体标本去向	使用后销毁	说明
Fate of sample：	Destruction after use	Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：

最小 Min age	50	岁 years
最大 Max age	85	岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

由Cenduit供应商根据相关统计方案进行集中随机分组

Randomization Procedure (please state who generates the random number sequence and by what method)：

Cenduit suppliers conduct centralized random grouping according to the relevant statistical plan

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：	双盲
Blinding：	Double blind

是否共享原始数据： IPD sharing	否No
共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：	NA
The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：	NA
数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：	诺华工作人员（或指定的CRO）将审查研究工作人员录入的数据的完整性、准确性和科学／医学合理性。发现差异值和缺失值后需创建电子数据质疑说明问题的性质并要求澄清，然后通过EDC系统发送给研究中心。要求指定的研究中心工作人员及时回复质疑，并对数据进行必要的修改。将使用世界卫生组织（WHO）药物参考列表（采用解剖学治疗学化学分类系统）对数据库中录入的伴随治疗和既往用药进行医学编码。采用国际医学用语词典（MedDRA）术语，对病史／当前医学病症和不良事件进行编码。将使用交互式应答技术（IRT）追踪筛选、随机化、筛选失败和研究完成日期、分配给受试者的所有研究治疗的随机化代码和数据以及所有的剂量变化。系统将由供应商提供，该供应商还将管理数据库。将在特定时间以电子方式将数据发送给诺华。代码揭盲功能将一直可用，直到研究关闭或诺华要求弃用。一旦完成所有必要操作并声明数据库完整且准确，数据库会锁定，治疗代码会揭盲并可供数据分析／由独立程序员和统计师转移至限制访问区域开展每项中期分析。
Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：	Monitoring strategy, methods, responsibilities, and requirements are provided in the monitoring plan and contracts. Details may include definition of study critical data items and processes (e.g., risk-based initiatives in operations and quality such as risk management and mitigation strategies and analytical risk-based monitoring), including handling of noncompliance issues and monitoring techniques (central, remote, or on-site monitoring)Records and documents, including signed ICFs, pertaining to the conduct of this study must be retained by the Investigator for 15 years after study completion unless local regulations or institutional policies require a longer retention period. No records may be destroyed during the retention period without the written approval of Novartis. No records may be transferred to another location or party without written notification to Novartis
数据与安全监察委员会： Data and Safety Monitoring Committee：	有/Yes
注册人： Name of Registration：	2025-12-03 18:00:04