NCT06335173进行中（未招募）2 期
A Phase 2 Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Intravenous Sabirnetug in Early Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 542
- 试验地点
- 68
- 主要终点
- Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy of sabirnetug infusions administered once every four weeks (Q4W) in slowing cognitive and functional decline as compared to placebo in participants with early Alzheimer's disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight of at least 30 kilograms (kg) (66 pounds [lbs]) and no more than 160 kg (352 lbs) at Screening
- •Must consent to apolipoprotein E4 (APOE4) genotype status assessment
- •Must meet all of the following criteria
- •National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) due to Alzheimer's Disease (AD) or probable AD
- •Screening score between 22 and 30 (inclusive) on the Mini-Mental State Examination (MMSE)
- •Screening score of 0.5 or 1.0 on the Clinical Dementia Rating Global Score (CDR-GS) and Screening score ≥0.5 on the CDR Memory Box score
- •Evidence of cerebral amyloid accumulation by either PET scan or CSF
- •If using cholinesterase inhibitors or memantine to treat symptoms related to AD, doses must be stable for at least three months (12 weeks) prior to Baseline and every attempt should be made to keep them at stable doses throughout the study
- •Must have a reliable informant or study partner who is willing and able to perform all the roles as specified in the study partner Informed Consent Form (ICF)
- •Female participants must be surgically sterile or be at least one-year post-menopausal. Male participants with a female partner of child-bearing potential must use adequate contraception
排除标准
- •Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI
- •MRI of the brain that is inconsistent with MCI or AD or results showing greater than four ARIA-H, presence of any ARIA-E, or superficial siderosis
- •History of significant or unstable neurological disease, other than AD, which may affect cognition or ability to complete the study, such as other dementias, serious infection of the brain, significant head trauma, uncontrolled seizures, stroke, or Parkinson´s disease
- •Current serious or unstable clinically important illness that, in the judgment of the site investigator, is likely to affect cognitive assessment including visual and hearing impairment or affect the participant's safety or ability to complete the study
- •Malignant disease in the last five years except for resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or in situ prostate cancer with a normal posttreatment prostate-specific antibody (PSA)
- •Geriatric Depression Scale-Short Form (GDS-SF) score >10 or current symptoms meeting Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V), criteria for major depressive disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the site investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant´s ability to complete the study
- •Suicide risk, as determined by meeting any of the following criteria:
- •Any suicide attempt or preparatory acts/behavior on the C-SSRS Baseline/Screening in the last six months
- •Suicidal ideation in the last six months as defined by a positive response to Question 5 (Suicidal Ideation) on the C-SSRS Baseline/Screening
- •Significant risk of suicide, as judged by the site investigator
- •Conditions that may affect cognitive assessments during the study
- •Alcohol use disorder and/or substance use disorder within the last five years
研究组 & 干预措施
DBT Period: sabirnetug 50 mg/kg
Experimental
Participants will receive sabirnetug, 35 mg/kg, for the first two doses, followed by sabirnetug, 50 mg/kg, Q4W as an IV infusion during the DBT period.
干预措施: sabirnetug (Drug)
DBT Period: Placebo
Placebo Comparator
Participants will receive sabirnetug matching placebo, Q4W as an IV infusion during the DBT period.
干预措施: Placebo (Drug)
Open-Label Extension (OLE) Period: sabirnetug 35 mg/kg
Experimental
Participants will receive sabirnetug, 35 mg/kg, Q4W as an IV infusion during the OLE period.
干预措施: sabirnetug (Drug)
Double-blind Treatment (DBT) Period: sabirnetug 35 mg/kg
Experimental
Participants will receive sabirnetug, 35 milligrams per kilogram (mg/kg), Q4W as intravenous (IV) infusion during the DBT period.
干预措施: sabirnetug (Drug)
结局指标
主要结局
Change from Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Score
时间窗: Baseline up to Week 80
iADRS is a validated composite of cognition and function made up of Alzheimer's Disease Assessment Scale - Cognitive Subscale 13-item (ADAS-Cog13) and the Alzheimer's Disease Cooperative Study - instrumental Activities of Daily Living scale (ADCS-iADL). ADAS-Cog13 is a rater-administered instrument consisting of 13 items assessing cognitive function areas most typically impaired in AD. ADAS-Cog13 scores range from 0 to 85, with higher scores indicating a greater deficit of global cognition. The ADCS-iADL is a subset of the 23-item ADCS-ADL (items 6a and 7 to 23). The iADLs are more complex skills required to successfully live independently. iADL-items score ranges from 0 to 59 (lower scores indicating greater impairment). The iADRS is calculated as a linear combination of total scores from the ADAS-Cog13 and ADCS-iADL. The iADRS score ranges from 0 to 144 with lower scores indicating worse performance.
次要结局
- Change from Baseline in ADCS-iADL Score(Baseline up to Week 80)
- Change from Baseline in ADAS-Cog13 Score(Baseline up to Week 80)
- Change from Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB)(Baseline up to Week 80)
- Change from Baseline in Mini-Mental State Examination (MMSE)(Baseline up to Week 80)
- Change from Baseline in Quality of Life in Alzheimer's Disease (QoL-AD)(Baseline up to Week 80)
- Change from Baseline in Neuropsychiatric Inventory Questionnaire (NPI-Q) Score(Baseline up to Week 80)
- Change from Baseline in EuroQoL 5-Dimension 5-Level (EQ-5D-5L)(Baseline up to Week 80)
- Change from Baseline in Resource Utilization in Dementia (RUD)(Baseline up to Week 80)
- Change from Baseline in Zarit Burden Interview (ZBI)(Baseline up to Week 80)
- Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by iADRS(Baseline up to Week 80)
- Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADCS-iADL(Baseline up to Week 80)
- Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by ADAS-Cog13(Baseline up to Week 80)
- Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by CDR-SB(Baseline up to Week 80)
- Effect of sabirnetug on Clinical Progression as Compared to Placebo Assessed Using Time Saved Analysis as Measured by MMSE(Baseline up to Week 80)
- Percentage of Participants with No Clinical Progression at One Year(Baseline up to Week 80)
- Number of Participants with Treatment-Related Adverse Events (TEAEs)(Baseline up to Week 80)
- Number of Participants with Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)(Baseline up to Week 80)
- Number of Participants who Discontinue or Withdraw due to TEAE(Baseline up to Week 80)
- Number of Participants with Anti-Drug Antibodies (ADA) and Neutralizing Antibodies(Baseline up to Week 80)
- Number of Participants with Amyloid-Related Imaging Abnormality with Edema/Effusions (ARIA-E) and ARIA with Hemorrhage/Hemosiderin Deposition (ARIA-H) as Measured by Magnetic Resonance Imaging (MRI)(Baseline up to Week 80)
- Number of Participants with Suicidal Ideation and Behavior as Measured by Columbia-Suicide Severity Rating Scale (C-SSRS)(Baseline up to Week 80)
- Serum Concentration of sabirnetug(Pre-dose and multiple timepoints post dose up to 80 weeks)
- Concentration of sabirnetug in Cerebrospinal Fluid (CSF)(Up to Week 76)
- CSF Concentrations of ACU193 in a Subset of Participants(Up to Week 76)
- Correlation Between sabirnetug Exposure with Clinical Efficacy Measures(Baseline up to 80 weeks)
- Change From Baseline in Amyloid Plaque Load or Deposition Measured by Positron Emission Tomography (PET) in Centiloids(Baseline up to Week 76)
- Change from Baseline in Volumetric Magnetic Resonance Imaging (vMRI) of Whole Brain Volume, Ventricular Volume, and Volume of Selected Regions of Interest(Baseline up to Week 76)
- Target Engagement Assessed by Measurement of sabirnetug- Amyloid-β oligomer (AβO) Complex in CSF(Up to Week 76)
- Change from Baseline in CSF Concentrations of Amyloid, Tau and Other Neurodegenerative Biomarkers(Baseline up to Week 76)
- Change from Baseline in CSF Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers in a Subset of Participants(Baseline up to Week 76)
- Change from Baseline in Blood Concentrations of Amyloid, Tau, and Other Neurodegenerative Biomarkers(Baseline up to Week 76)
- Correlation Between Change in Biomarker that Reflect Disease Progression and Clinical Changes(Up to 80 weeks)
研究者
研究点 (68)
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