A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Dementia with Lewy Bodies
一项随机、双盲、安慰剂对照、平行组、2 期研究,旨在评估 CT1812 在路易体痴呆受试者中的安全性和有效性
基本信息
- 批准号:10674687
- 负责人:
- 金额:$ 847.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-05-15 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAdverse eventAlzheimer&aposs DiseaseAlzheimer&aposs disease patientAmyloid beta-ProteinAutopsyBindingBinding SitesBiological MarkersBiologyBrainCell membraneCenters of Research ExcellenceCerebrospinal FluidCerebrospinal Fluid ProteinsClinicalClinical TreatmentClinical TrialsCognitionCognitiveComplexConduct Clinical TrialsDataDementiaDementia with Lewy BodiesDevelopmentDiseaseDisease ProgressionDoseDouble-Blind MethodDrowsinessEquipment and supply inventoriesFamilyFamily CaregiverFunctional disorderHeadacheHealth Care CostsIn VitroLewy Body DementiaLightMeasurementMeasuresMediatingMental disordersModificationMolecularMovement Disorder Society Unified Parkinson&aposs Disease Rating ScaleNerve DegenerationNeuronsOutcomeParkinson DiseasePathologyPatientsPharmaceutical PreparationsPharmacodynamicsPhasePhase II Clinical TrialsPlacebo ControlPlacebosPlasmaQuality of lifeRandomizedResearchResearch PersonnelSafetyShapesSynapsesSynaptosomesTestingTherapeuticUniversitiesabeta oligomeralpha synucleinclinical candidateclinical developmentclinical efficacycognitive functioncognitive performancecognitive testingcooperative studydesigndrug candidateexperiencehealthy volunteerimpressionimprovedinvestigator-initiated trialmonomerneurodegenerative dementianeurofilamentneurograninneuropsychiatrynoveloff-label usepatient populationphase 2 studyphase II trialphosphoneuroprotein 14preclinical studypreventprimary outcomeprogramsprotein biomarkersprotein complexreceptorsafety assessmentsafety outcomessigma-2 receptorsmall moleculesymptom treatmentsynaptosomal-associated protein 25synaptotagmintargeted biomarkertau Proteinstau-1therapeutic candidate
项目摘要
ABSTRACT: Cognition Therapeutics, Inc. (CogRx) is developing CT1812 for neurodegenerative conditions,
including Dementia with Lewy Bodies (DLB). This first-in-class small molecule drug candidate selectively
displaces Aβ oligomers bound to neuronal receptors at synapses and protects synapses from toxic oligomer
effects, clearing them from the brain into the cerebrospinal fluid (CSF). CT1812 also displaces α-synuclein
oligomer binding to neurons in vitro. CT1812 is currently in a Phase 2 trial in patients with mild to moderate
Alzheimer's disease (AD), where it has been found to be safe and generally well-tolerated. When administered
once daily for 28 days to AD patients, CT1812 significantly reduced concentrations of synaptic degeneration
markers in CSF. Similar to Aβ oligomers, α-synuclein oligomers bind to neurons and cause synaptic dysfunction
and loss, spreading throughout the brain as disease progression is observed in DLB. Eighty percent of patients
with DLB reflect both Aβ and α-synuclein pathology at autopsy. Patients with DLB likely have both types of
oligomers and should benefit from treatment with CT1812.
This clinical trial project proposes to conduct a Phase 2 randomized, double-blind, placebo-controlled, six-month
study to evaluate the safety, tolerability, and exploratory efficacy of CT1812 at 100 mg and 300 mg daily doses
in mild to moderate DLB patients (N=40/group). Trial endpoints will include safety as well as exploratory efficacy
measures (Montreal Cognitive Assessment [MoCA], Cognitive Drug Research Battery [CDR], Clinician
Assessment of Fluctuation [CAF], Epworth Sleepiness Scale [ESS], Movement Disorder Society – Unified
Parkinson's Disease Rating Scale – Part III [MDS-UPDRS3], The Alzheimer's Disease Cooperative Study –
Clinical Global Impression of Change [ADCS-CGIC], ADCS-Activities of Daily Living [ADL], and Neuropsychiatric
Inventory [NPI]) at baseline, 3 months, and 6 months. Additional measurements of plasma and CSF
concentrations of drug, target engagement biomarkers (including Aβ and α-synuclein oligomers), disease
progression protein markers (Aβ and α-synuclein monomer, total and phosphorylated tau protein) and synaptic
damage/neurodegeneration biomarkers (neurogranin, synaptotagmin, synaptosomal-associated protein 25
[SNAP-25], and neurofilament light [NFL]) at baseline and at 6 months will allow correlation of drug
concentrations with measures of synaptic damage and cognitive performance. Conducting a study with this
patient population will leverage the ongoing CT1812 development efforts for AD and will provide a near-term
opportunity to investigate a clinical candidate therapeutic in DLB, an indication for which no disease-modifying
treatments exist. Completion of this study will provide an initial assessment of CT1812 efficacy in DLB patients
that will inform design of subsequent pivotal trials necessary for further clinical development of CT1812.
摘要:认知治疗公司(CogRx)正在开发针对神经退行性疾病的CT1812,
包括路易体痴呆(DLB)。这种一流的小分子药物候选药物选择性地
取代与突触上神经元受体结合的β寡聚体并保护突触免受毒性寡聚体的影响
作用,将它们从大脑清除到脑脊液(CSF)中。CT1812还取代了α-突触核蛋白
低聚物在体外与神经元结合。CT1812目前处于轻中度患者的2期试验中
阿尔茨海默病(AD),已被发现是安全的,通常耐受性良好。当给药时
对于AD患者,CT1812每天一次,持续28天,显著降低突触变性的浓度
脑脊液中的标志物。与β寡聚体类似,α-突触核蛋白寡聚体与神经元结合并导致突触功能障碍
以及丢失,随着疾病的进展在DLB中蔓延到整个大脑。80%的患者
尸检同时反映Aβ和α-突触核蛋白病理。DLB患者可能同时患有这两种类型的
低聚物,并应受益于CT1812的治疗。
该临床试验项目建议进行2期随机、双盲、安慰剂对照、为期6个月的临床试验
评价CT1812每日100 mg和300 mg剂量的安全性、耐受性和探查效果的研究
轻至中度DLB患者(N=40例/组)。试验终点将包括安全性和探索性疗效。
措施(蒙特利尔认知评估[MoCA]、认知药物研究组合[CDR]、临床医生
波动评估[CAF],爱普沃斯嗜睡量表[ESS],运动障碍社会--统一
帕金森氏病评定量表-第三部分[MDS-UPDRS3],阿尔茨海默病合作研究-
临床总体变化印象[ADCS-CGIC]、ADCS-日常生活活动[ADL]和神经精神病学
库存[NPI])按基准、3个月和6个月计算。血浆和脑脊液的附加测量
药物浓度、靶向结合生物标志物(包括Aβ和α-突触核蛋白寡聚体)、疾病
进展蛋白标记物(Aβ和α-突触核蛋白单体、总的和磷酸化的tau蛋白)与突触
损伤/神经变性生物标记物(神经颗粒素、突触素、突触体相关蛋白25
[Snap-25]和神经丝光线[NFL])将允许药物相关性
通过测量突触损伤和认知表现来集中注意力。用这个进行一项研究
患者群体将利用正在进行的针对AD的CT1812开发工作,并将在短期内提供
有机会研究DLB的临床候选治疗方法,这是一个没有疾病修改的适应症
治疗方法是存在的。这项研究的完成将为CT1812在DLB患者中的疗效提供初步评估
这将为CT1812进一步临床开发所需的后续关键试验的设计提供信息。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ANTHONY O CAGGIANO其他文献
ANTHONY O CAGGIANO的其他文献
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{{ truncateString('ANTHONY O CAGGIANO', 18)}}的其他基金
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Dementia with Lewy Bodies
一项随机、双盲、安慰剂对照、平行组、2 期研究,旨在评估 CT1812 在路易体痴呆受试者中的安全性和有效性
- 批准号:
10187183 - 财政年份:2021
- 资助金额:
$ 847.91万 - 项目类别:
Human AME study of CT1812, a small molecule in phase 2 clinical trials for the treatment of Alzheimer's disease
CT1812 的人体 AME 研究,这是一种小分子,处于治疗阿尔茨海默病的 2 期临床试验中
- 批准号:
10247968 - 财政年份:2021
- 资助金额:
$ 847.91万 - 项目类别:
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Dementia with Lewy Bodies
一项随机、双盲、安慰剂对照、平行组、2 期研究,旨在评估 CT1812 在路易体痴呆受试者中的安全性和有效性
- 批准号:
10402396 - 财政年份:2021
- 资助金额:
$ 847.91万 - 项目类别:
A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects with Mild to Moderate Alzheimerʼs Disease
一项旨在评估 CT1812 治疗对轻度至中度阿尔茨海默病受试者突触活动影响的脑电图 (EEG) 试验研究
- 批准号:
10651320 - 财政年份:2019
- 资助金额:
$ 847.91万 - 项目类别:
A Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Phase II Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Mild to Moderate Alzheimer's Disease
一项随机、双盲、安慰剂对照、平行组、II 期研究,旨在评估 CT1812 在轻度至中度阿尔茨海默病受试者中的安全性和有效性
- 批准号:
10170636 - 财政年份:2018
- 资助金额:
$ 847.91万 - 项目类别:
A Randomized, Double-blind, Placebo-Controlled, Parallel-Group, Phase II Study to Evaluate the Safety and Efficacy of CT1812 in Subjects with Mild to Moderate Alzheimerʼs Disease
一项随机、双盲、安慰剂对照、平行组、II 期研究,旨在评估 CT1812 在轻度至中度阿尔茨海默病受试者中的安全性和有效性
- 批准号:
10208480 - 财政年份:2018
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Translational Development of Glial Growth Factor 2 (GGF2) for the Treatment of St
神经胶质生长因子 2 (GGF2) 用于治疗 ST 的转化开发
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Molecular Evolution of Chondroitinase ABCI for SCI
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Release Chondroitinase Systems for Spinal Cord Injury
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- 资助金额:
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