A Placebo-Controlled, Double-Blind, Parallel-Group, 24 Month Study With an Open-Label Extension Phase to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Subjects With Early Alzheimer's Disease
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 2,212
- 试验地点
- 18
- 主要终点
- Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score
研究概览
简要总结
The name of this trial is MissionAD1. This phase 3 study consists of a Core and Open Label Extension (OLE) Phase in participants with Early Alzheimer's Disease (EAD), and will be conducted to evaluate the efficacy and safety of E2609. The Core is a 24-month treatment, multicenter, double blind, placebo controlled parallel group study. The OLE is a 24-month treatment, one group study. The data for the studies E2609-G000-301 (NCT02956486, MissionAD1) and E2609-G000-302 (NCT03036280, MissionAD2) will be pooled.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mild cognitive impairment due to Alzheimer's disease (AD) or mild AD dementia including
- •Mini Mental State Examination score equal to or greater than 24
- •Clinical Dementia Rating (CDR) global score of 0.5
- •CDR Memory Box score of 0.5 or greater
- •Impaired episodic memory confirmed by a list learning task
- •Positive biomarker for brain amyloid pathology as indicated by either amyloid positron emission tomography or cerebrospinal fluid AD assessment or both
- •Extension Phase
- •Participants who complete the Core Study
排除标准
- •Females who are breastfeeding or pregnant at Screening or Baseline. Females of child-bearing potential must use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation
- •Any condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD
- •Participants with a history of seizures within 5 years of Screening
- •History of transient ischemic attacks or stroke within 12 months of Screening
- •Psychiatric diagnosis or symptoms (example, hallucinations, major depression, delusions etc.)
- •Suicidal ideation or any suicidal behavior within 6 months before Screening or has been hospitalized or treated for suicidal behavior in the past 5 years
- •Have any contraindications to magnetic resonance imaging (MRI) scanning or
- •Have lesions that could indicate a dementia diagnosis other than AD on brain MRI
- •Exhibit other significant pathological findings on brain MRI.
- •Participants who have a history of moderate to severe hepatic impairment (example, Child-Pugh Class B or C)
- •Results of laboratory tests conducted during Screening that are outside the following limits:
- •Absolute lymphocyte count below the lower limit of normal (LLN)
- •Thyroid stimulating hormone above normal range
- •Abnormally low Vitamin B12 levels
- •Participants at increased risk of infection
- •Have received any live vaccine/live attenuated vaccine in the 3 months before randomization
- •Any chronic inflammatory disease that is not adequately controlled or that requires systemic immunosuppressive or immunomodulatory therapy
- •Any other clinically significant abnormalities
- •Severe visual or hearing impairment
- •A prolonged corrected QT (QTc) interval (QT interval with Fridericia's correction [QTcF] greater than 450 milliseconds [ms])
- •Malignant neoplasms within 5 years of Screening
- •Known or suspected history of drug or alcohol abuse
- •Taking prohibited medications, which must be reviewed with the Investigator
- •Have participated in a recent clinical study
- •Note: Other protocol-defined Inclusion/Exclusion Criteria may apply.
研究组 & 干预措施
Core Study: Elenbecestat 50 mg
Participants will receive one 50 milligram (mg) elenbecestat tablet, orally, once a day in the morning. The core study will be double blinded.
干预措施: Elenbecestat (Drug)
Core Study: Placebo
Participants will receive one matching placebo tablet, orally, once a day in the morning. The core study will be double blinded.
干预措施: Placebo (Drug)
Open-label Extension Phase: Elenbecestat 50 mg
Participants completing the core study will receive one 50 mg elenbecestat tablet, orally, once a day in the morning.
干预措施: Elenbecestat (Drug)
结局指标
主要结局
Core Phase: Change From Baseline up to Month 24 in the Clinical Dementia Rating-sum of Boxes (CDR-SB) Score
时间窗: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase
The clinical dementia rating (CDR) scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.
Extension Phase: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase
A TEAE is defined as an adverse event that emerged during treatment or within 28 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event was continuous. Number of participants with TEAEs (serious and non-serious adverse events) were reported based on their safety assessments of laboratory tests, suicidal ideation and suicidal behavior, drug abuse potential, physical examination, neurological examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values.
次要结局
- Core Phase: Change From Last Dose in the CDR-SB Score(From last dose in the core phase (up to Month 24) up to 3 months follow up (up to Month 27))
- Core Phase: Change Per Year (Mean Slope) in CDR-SB Score up to Month 24(Up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in the ADCOMS for Participants Enriched by Baseline Amyloid PET SUVR Between 1.2 and 1.6(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Time to Conversion to Dementia for Participants Who Were Not Clinically Staged as Having Dementia at the Core Phase Baseline up to Month 24(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in Alzheimer's Disease Composite Score (ADCOMS)(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in Amyloid Positron Emission Tomography (PET) Standardized Uptake Value Ratio (SUVR)(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Time to Worsening of CDR Score up to Month 24(Up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in the MMSE Score(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Last Dose in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score(From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27))
- Core Phase: Change From Baseline up to Month 24 in the CDR-SB Score for Participants Enriched by Baseline Amyloid PET SUVR Between 1.2 and 1.6(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in the Functional Assessment Questionnaire (FAQ) Score(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition14 (ADAS-Cog14) Score(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Last Dose in the ADAS-cog11 Score(From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27))
- Core Phase: Change From Last Dose in the ADAS-cog14 Score(From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27))
- Extension Phase: Time to Conversion to Dementia for Participants Who Were Not Clinically Staged as Having Dementia at the Core Phase Baseline up to Month 12 of the Extension Phase(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Core Phase: Change From Baseline up to Month 24 in the ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Baseline up to Month 24 in the Alzheimer's Disease Assessment Scale-cognition11 (ADAS-Cog11) Score(Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase)
- Core Phase: Change From Last Dose in the ADCOMS(From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27))
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADCOMS(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in MMSE Score(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Core Phase: Change From Last Dose in the MMSE Score(From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27))
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in FAQ Score(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Word List (Immediate Recall and Delayed Recall) Score(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in CDR-SB Score(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)
- Extension Phase: Change From Core Phase Baseline up to Month 12 of the Extension Phase in ADAS-cog14 Score(Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase)