A Multicentre,Randomised, Double-blind, Placebo-controlled, 3-arm, 24-week Parallel-group Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of ORY-2001 in Patients With Mild-moderate Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- Treatment Emergent Adverse Events
研究概览
简要总结
This is a Phase IIa study assessing the safety, tolerability and preliminary efficacy of ORY-2001 in mild to moderate Alzheimer's Disease patients.
详细描述
This phase IIa study is a double-blind, randomized, parallel-group and multicenter study with a placebo-controlled 24-week treatment period followed by a no placebo-controlled 24-week extension period.
It is planned to randomise 25 patients. In the double-blind placebo-controlled treatment period, all patients will be randomized between two doses of ORY-2001 and placebo. In the double-blind no placebo-controlled extension period, patients in the placebo arm will be re-allocated in one of the two different dose levels of ORY-2001. Randomization will be stratified by cognitive impairment severity.
An independent Data Monitoring Committee (DMC) will review un-blinded safety data throughout the study.
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
- •Probable Alzheimer's Disease (AD) diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria
- •MMSE score at Screening and Baseline Visits of at least 16 and not greater than 26
- •Evidence of the AD pathophysiological process indicated by decreased levels of amyloid antigen binding (AB) and increased levels of total Tau protein or phospho-Tau protein in cerebrospinal fluid (CSF)
- •Outpatient consulting a general practitioner, or a psychiatrist/neurologist/geriatrician
- •Knowledgeable and reliable close relative/caregiver who will accompany the patient to all clinic visits during the study
- •Daily treatment with the same acetylcholinesterase inhibitor on a stable dose
- •Fertile male and female must use highly effective contraception, from the Screening Visit until 90 days after last dose.
- •Signed informed consent by patient (or legal representative, if applicable) and a close relative/caregiver prior to the initiation of any study specific procedure
排除标准
- •Failure to perform screening or baseline examinations
- •Hospitalization or change of concomitant medication 1 month prior to Screening visit or during Screening Period
- •Clinical, laboratory or neuroimaging findings consistent with:
- •Other primary degenerative dementia;
- •Other neurodegenerative condition;
- •Cerebrovascular disease;
- •Other central nervous system diseases;
- •A current Diagnostic and Statistical Manual-5 (DSM-5) diagnosis of major depression, schizophrenia or bipolar disorder
- •Positive results for tuberculosis, human immunodeficiency virus (HIV), hepatitis C or hepatitis B (hepatitis B surface antigen [HbsAg]) serology at the Screening Visit
- •Clinically significant, advanced or unstable disease that may interfere with evaluation.
- •Disability that may prevent the patients from completing all study requirements.
- •Chronic drug intake of forbidden concomitant medication.
- •Treatment with anti-amyloid beta or anti-Tau protein monoclonal antibodies or other disease modifying strategies within three months or five half-lives, whichever is longer, prior to the Screening Visit
- •Treatment with an active vaccine targeting amyloid beta or Tau protein
- •Suspected or known drug or alcohol abuse
- •Metallic implants or any other cause precluding the performance of brain MRI
- •Enrolment in another investigational study or intake of investigational drug within the previous 3 months since the last dose
- •Suicide attempt within the last year or significant risk of suicide (in the opinion of the investigator, defined as a "yes" to suicidal ideation questions 4 or 5, or answering "yes" to suicidal behavior on the Columbia-Suicide Severity Rating Scale within the past 12 months)
- •Any condition that in the opinion of the investigator makes the patient unsuitable for inclusion in the study
研究组 & 干预措施
ORY-2001 Low dose
0.6mg ORY-2001 capsule
干预措施: ORY-2001 Low dose (Drug)
ORY-2001 High dose
1.2mg ORY-2001 capsule
干预措施: ORY-2001 High dose (Drug)
Placebo
Placebo capsule
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment Emergent Adverse Events
时间窗: Week 48
Number, frequency and severity of Treatment Emergent Adverse Events (TEAEs) including serious TEAEs.
Withdrawn patients due to TEAEs
时间窗: Week 48
Number and percentage of withdrawn patients due to TEAEs
次要结局
- 14-item Alzheimer's Disease Assessment Scale-Cognitive(48 weeks)
- Computerized Cognitive Test battery(48 weeks)
- Mini-Mental State Examination (MMSE)(48 weeks)
- Clinical Dementia Rating Scale Sum of Boxes(48 weeks)
- Cornell Scale for Depression in Dementia (CSDD)(48 weeks)
- Cohen-Mansfield Agitation Inventory (CMAI)(48 weeks)
- Clinician version of the Apathy Evaluation Scale (AES-C)(48 weeks)