A Phase II, Multicenter, Open-Label, Single Arm Study to Evaluate the Pharmacodynamic Effects of Once Weekly Administration of Gantenerumab in Participants With Early (Prodromal to Mild) Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 192
- 试验地点
- 34
- 主要终点
- Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan
研究概览
简要总结
This is a Phase II, multicenter, open-label, single arm, PD study in participants with early (prodromal to mild) AD to evaluate the effect of a once weekly (Q1W) dosing regimen of gantenerumab on deposited amyloid as measured by change from baseline to Week 104 (primary) and Week 208 in brain amyloid positron emission tomography (PET). The administration of gantenerumab as a single injection of Q1W will be investigated in this study, to simplify the dosing regimen for participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Probable Alzheimer's Disease (AD) dementia or prodromal AD.
- •Availability of a reliable study partner (non-professional caregiver) who accepts to participate in study procedure throughout the study duration
- •The participant should be capable of completing all aspects of study assessments including MRI, clinical genotyping, and PET imaging, either alone or with the help of the study partner (non-professional caregiver).
- •Adequate visual and auditory acuitysufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted).
- •Evidence of AD pathological process, as confirmed by amyloid PET scan by qualitative read by the core/central PET laboratory.
- •Prodromal or mild symptomatology, as defined by a screening Mini-Mental State Examination (MMSE) score >/=22 and Clinical Dementia Rating global score (CDR-GS) of 0.5 or 1.0, as well as a clinical dementia rating (CDR) memory domain score >/=0.
- •If the participant is receiving symptomatic AD medications, a stable dosing regimen for at least 3 months prior to screening and until start of study treatment.
- •Agreement not to donate blood or blood products for transfusion for the duration of the study and for 1 year after final dose of study drug.
- •Agreement not to participate in other research studies for the duration of this trial, unless these are related Roche-sponsored non-interventional studies.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods hat result in a failure rate of < 1% per year during the treatment period and for at least 16 weeks after the final dose of study drug.
排除标准
- •Any evidence of a condition other than AD that may affect cognition.
- •History or presence of clinically evident systemic vascular disease that in the opinion of the investigator has the potential to affect cognitive function.
- •History or presence of clinically evident cerebrovascular disease.
- •History or presence of posterior reversible encephalopathy syndrome.
- •History or presence of any stroke with clinical symptoms within the past 12 months, or documented history within the last 6 months of an acute event that is consistent with a transient ischemic attack.
- •History of severe, clinically significant CNS trauma.
- •History or presence of intracranial mass that could potentially impair cognition.
- •Presence of infections that affect brain function or history of infections that resulted in neurologic sequelae.
- •History or presence of systemic autoimmune disorders that potentially cause progressive neurologic disease with associated cognitive deficits.
- •History of schizophrenia, schizoaffective disorder, major depression, or bipolar disorder.
- •At risk for suicide in the opinion of the investigator.
- •Alcohol and/or substance abuse or dependants in past 2 years.
研究组 & 干预措施
Gantenerumab
Participants will receive gantenerumab by subcutaneous (SC) injection at a dose of 120 mg every 4 weeks (Q4W) for 12 weeks, followed by 255 mg Q4W for 12 weeks, and 255 mg every 2 weeks (Q2W) for another 12 weeks, followed by the target dose 255 mg once weekly (Q1W) for up to Week 103. Participants who complete Week 104 visit will be given an option to take part in 2-year extension of the study to receive gantenerumab 255 mg Q1W for up to Week 207.
干预措施: Gantenerumab (Drug)
结局指标
主要结局
Change From Baseline in Brain Amyloid Load at Week 104 as Measured by [18F] Florbetaben Positron Emission Tomography (PET) Scan
时间窗: Baseline, Week 104
Screening amyloid PET scan was considered baseline evaluation.Brain amyloid load was quantified in terms of Standardized Uptake Value Ratio (SUVR),defined as ratio of tracer uptake in cortical composite target region of interest(ROI)to tracer uptake in reference ROI.Composite region: frontal,parietal,temporal,posterior cingulate cortex,anterior cingulate cortex. Reference ROI (whole cerebellum) was represented by weighted average of Cerebellum Ventral,Cerebellum Dorsal (left/right), Cerebellar White Matter.SUVR linearly transformed to standardized Centiloid Scale (CL) using formula CL=175.6xSUVR-174.2.CL ranges from \<0 to \>100, anchor points are 0=high-certainty amyloid negative scan and 100=amount of global amyloid deposition found in typical AD scan.
次要结局
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Number of Participants With Amyloid-Related Imaging Abnormalities-Haemosiderin Deposition (ARIA-H) Confirmed by Magnetic Resonance Imaging (MRI)(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Number of Participants With Amyloid-Related Imaging Abnormalities-Edema (ARIA-E) Confirmed by Magnetic Resonance Imaging (MRI)(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Number of Caregiver or Study Partner With Responses to Home Administration Questionnaire (HAQ)(Weeks 36, 52, 76, 104)
- Number of Participants With Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Number of Participants With Injection-Site Reactions (ISR)(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Number of Participants With Treatment-emergent Anti-Drug Antibodies to Gantenerumab(From day of first dose up to 16 weeks after the last dose (up to 120 weeks))
- Plasma Concentration of Subcutaneous (SC) Gantenerumab at Specified Timepoints(Day 4 of Week 1, Week 24, 36, 52, and 76)
- Change in Brain Amyloid Based on Different Dosing Frequency(Baseline up to Week 52)