A Phase III, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Efficacy and Safety Study of Gantenerumab in Patients With Mild Alzheimer's Disease; Part II: Open-Label Extension For Participating Patients
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 389
- 试验地点
- 131
- 主要终点
- Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)
研究概览
简要总结
Part 1 is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of gantenerumab in participants with mild Alzheimer disease. Participants will be randomized to receive either gantenerumab subcutaneously every 4 weeks or placebo subcutaneously every 4 weeks. Approved Alzheimer medication is allowed if on stable dose for 3 months prior to screening. Part 2 is an open-label extension (OLE).
A positron emission tomography (PET) imaging substudy will be conducted within the main study. Eligible participants who provide separate informed consent will undergo PET imaging scans using the radioligand florbetapir as a pharmacodynamic measure of changes in brain amyloid load over time.
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
- Double (Participant, Investigator)
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
- •Clinical diagnosis of probable mild Alzheimer disease (AD) based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria or major NCD based whether or not receiving AD approved medication
- •Cerebral spinal fluid (CSF) result consistent with the presence of amyloid pathology
- •Availability of a person ('caregiver') who in the investigator's judgment has frequent and sufficient contact with the participant, and is able to provide accurate information regarding the participant's cognitive and functional abilities
- •Fluency in the language of the tests used at the study site
- •Willingness and ability to complete all aspects of the study
- •Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing (eye glasses and hearing aids are permitted)
- •If currently receiving approved medications for AD, the dosing regimen must have been stable for 3 months prior to screening
- •Agreement not to participate in other research studies for the duration of this trial and its associated substudies
- •PART 2 - All participants who have been randomized and are actively participating in the study are eligible for Part 2
排除标准
- •Dementia or neurocognitive disorder (NCD) due to a condition other than AD, including, but not limited to, frontotemporal dementia, Parkinson disease, dementia with Lewy bodies, Huntington disease, or vascular dementia
- •History or presence of clinically evident vascular disease potentially affecting the brain that in the opinion of the investigator has the potential to affect cognitive function
- •History or presence of stroke within the past 2 years or documented history of transient ischemic attack within the last 12 months
- •History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease with associated cognitive deficits
- •History of schizophrenia, schizoaffective disorder, or bipolar disorder
- •Alcohol and/or substance use disorder (according to the DSM-5) within the past 2 years (nicotine use is allowed)
- •History or presence of atrial fibrillation
- •Within the last 2 years, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, angina pectoris, cardiac failure New York Heart Association Class II or higher)
- •Uncontrolled hypertension
- •Chronic kidney disease
- •Impaired hepatic function
- •PET imaging substudy, in addition to above:
- •Prior participation in other research study or clinical care within the last year such that the total radiation exposure would exceed the local or national annual limits
- •Part 2 Participants who have been discontinued from the study
研究组 & 干预措施
Part 1 (Double Blind treatment): Placebo
Participants received matching placebo by subcutaneous (SC) injection every 4 weeks (Q4W) up to 100 weeks during Part 1 of the study.
干预措施: Placebo (Drug)
Part 1 (Double Blind treatment): Gantenerumab
Participants received 105 mg Gantenerumab by SC injection Q4W for 24 weeks and if eligible 225 mg SC injection Q4W from weeks 28-100 during Part 1 of the study.
干预措施: Gantenerumab (Drug)
Part 2 (Open-Label Extension [OLE] treatment): Placebo switched to Gantenerumab Up to 1200 mg
Participants who had received Placebo in Part 1, received Gantenerumab at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
干预措施: Placebo (Drug)
Part 2 (OLE treatment): Gantenerumab up to 1200 mg
Participants who had received Gantenerumab in Part 1, received treatment at doses up to 1200 mg by SC injection Q4W for up to 2 years. Additionally, participants were given the option to continue receiving open-label gantenerumab treatment for 3 years.
干预措施: Gantenerumab (Drug)
结局指标
主要结局
Part 2: Percentage of Participants With Treatment Emergent Anti-Drug Antibodies (ADAs)
时间窗: First dose up to last dose (Baseline up to until maximum 5 years)
Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for participants previously (in part 1) on Gantenerumab and Placebo. The prevalence of ADA at baseline was calculated as the percentage of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the percentage of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.
Part 2: Percentage of Participants With Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: First dose up to 4 weeks after the last dose of study drug (up to 249 weeks)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. SAE is any adverse event that is fatal or which requires or prolongs inpatient hospitalization or results in persistent or significant disability/incapacity or causes congenital anomaly/birth defect or results in a significant medical event in the investigator's judgment.
Part 2: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment
时间窗: First dose up to 4 weeks after the last dose in OLE (Up to approximately 249 weeks)
Percentage of participants with adverse events leading to discontinuation from treatment were reported.
次要结局
- Part 2: Percent Change From Baseline in Cortical Thickness at Week 104(Baseline (Part 1 screening), Week 104)
- Part 1: Percentage of Participants With Adverse Events Leading to Discontinuation of Treatment(First dose up to last dose (Up to approximately 152 weeks))
- Part 2: Percent Change From Baseline in Hippocampal Volume at Week 104(Baseline (Part 1 screening), Week 104)
- Part 1: Gantenerumab Plasma Concentration at Multiple Timepoints(Pre-dose: Weeks 4, 8, 12, 24, 48, 72 and Post dose: Day 4)
- Part 2: Percent Change From Baseline in Whole Brain Volume at Week 104(Baseline (Part 1 screening), Week 104)
- Part 2: Ventricular Volume as Measured by MRI at Week 104(Part 2: Week 104)
- Part 1: Percentage of Participants With Treatment Emergent ADAs(First dose up to last dose (Up to approximately 152 weeks))
- Part 2: Gantenerumab Plasma Concentration at Multiple Timepoints(Pre-dose: Weeks 104, 116, 156, 208; Post-dose: Weeks 53, 101)
- Part 2: Change From Baseline in Brain Amyloid Load at Week 156 in a Subset of Participants(Baseline, Week 156)
- Part 1: Percentage of Participants With AEs, SAEs(First dose up to last dose (Up to approximately 152 weeks))