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A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab

2020年2月18日 更新者：Genentech, Inc.

A Multicenter, Open-Label, Long-Term Safety Extension of Phase II Studies ABE4869g and ABE4955g in Patients With Mild to Moderate Alzheimer's Disease

This Phase II, open-label extension (OLE), multicenter study will evaluate the long-term safety and tolerability of crenezumab in participants with mild to moderate Alzheimer's disease who have participated in and completed the treatment period of the Phase II Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578). Participants who received placebo in Study ABE4869g (NCT01343966) or ABE4955g (NCT01397578) will receive crenezumab. Anticipated time on study treatment is 144 weeks.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

360

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 加拿大
    • British Columbia
      • Kelowna、British Columbia、加拿大、V1Y 3G8
        • The Med Arts Health Rsrch Grp
      • Vancouver、British Columbia、加拿大、V6T 2B5
        • University of British Columbia Hospital; Division of Neurology
    • Nova Scotia
      • Halilfax、Nova Scotia、加拿大、B3H 2E1
        • Capitol District Health Authority
    • Ontario
      • Burlington、Ontario、加拿大、L7M 4Y1
        • JBN Medical Diagnostic Services Inc.
      • Kingston、Ontario、加拿大、K7L 2V7
        • Hotel Dieu Hospital
      • London、Ontario、加拿大、N6C 5J1
        • St. Joseph's HC-Parkwood Hosp
      • Ottawa、Ontario、加拿大、K1N 5C8
        • Bruyere Continuing Care
      • Peterborough、Ontario、加拿大、K9H 2P4
        • Kawartha Centre - Redefining Healthy Aging
      • Toronto、Ontario、加拿大、M3B 2S7
        • Toronto Memory Program (Neurology Research Inc.)
    • Quebec
      • Greenfield Park、Quebec、加拿大、J4V 2J2
        • Clinique Neuro Rive-Sud
      • Montreal、Quebec、加拿大、H1T 2M4
        • Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique
      • Quebec City、Quebec、加拿大、G1J 1Z4
        • CHAUQ Hopital Enfant-Jesus
      • Verdun、Quebec、加拿大、H4H 1R3
        • McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
  • 德国
      • Berlin、德国、12203
        • Univ Berlin; Klin fur Psychi & Psycho Charite
      • Günzburg、德国、89312
        • Bezirkskrankenhaus Günzburg
      • Mannheim、德国、68159
        • Zentralinstitut fuer Seelische Gesundheit
      • Munchen、德国、81377
        • Ludwig-Maximilians-Univ.
      • Munchen、德国、81675
        • Klinikum rechts der Isar der Technischen Universität München
      • Tubingen、德国、72076
        • Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
  • 法国
      • Bron、法国、69677
        • Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
      • Limoges、法国、87042
        • CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
      • Nancy、法国、54035
        • Hopital Central; Neurologie
      • Nantes、法国、44093
        • Hôpital Nord Laennec
      • Rouen、法国、76031
        • CHU de Rouen Hopital; Service de Neurologie
      • Strasbourg、法国、67091
        • Hôpital Civil de Strasbourg
  • 美国
    • Arizona
      • Phoenix、Arizona、美国、85006
        • Banner Alzheimer's Institute
      • Scottsdale、Arizona、美国、85259
        • Mayo Clinic
      • Sun City、Arizona、美国、85351
        • Banner Sun Health Research Insitute
    • California
      • Encino、California、美国、91316
        • Pharmacology Research Inst
      • Fresno、California、美国、93720
        • Margolin Brain Institute
      • La Jolla、California、美国、92037
        • Univ of CA San Diego; Neurosciences Comp.Alzheimer's
      • Los Angeles、California、美国、90095
        • University of California Los Angeles (UCLA)
      • Los Angeles、California、美国、90033
        • USC School of Medicine
      • Newport Beach、California、美国、92660
        • Pharmacology Research Inst
      • Oxnard、California、美国、93030
        • Pacific Neuroscience Med Grp
      • Palo Alto、California、美国、94304
        • Stanford Univ Medical Center
      • Sacramento、California、美国、95817
        • University of California Davis Medical System
      • San Diego、California、美国、92103
        • Pacific Research Network - PRN
      • San Francisco、California、美国、94117
        • Uni of California San Francisco
      • Santa Rosa、California、美国、95403
        • Redwood Regional Medical Group
    • Connecticut
      • New Haven、Connecticut、美国、06511
        • Yale University
    • Florida
      • Boca Raton、Florida、美国、33431
        • Florida Atlantic University; College of Medicine
      • Brooksville、Florida、美国、34601
        • Meridien Research
      • Delray Beach、Florida、美国、33445
        • Brain Matters Research, Inc.
      • Miami、Florida、美国、33137
        • Miami Jewish Health Systems; Clinical Research
      • Naples、Florida、美国、34105
        • Collier Neurologic Specialists
      • Orlando、Florida、美国、32806
        • Bioclinica Research
      • Tampa、Florida、美国、33609
        • Axiom Clinical Research of Florida
      • West Palm Beach、Florida、美国、33407
        • Premiere Research Institute
    • Georgia
      • Decatur、Georgia、美国、30033
        • DeKalb Neurology Associates
    • Illinois
      • Chicago、Illinois、美国、60612
        • Rush Alzheimer's Disease Cntr.
      • Elk Grove Village、Illinois、美国、60007
        • Alexian Brothers Neurosci Inst
    • Indiana
      • Indianapolis、Indiana、美国、46202
        • Indiana Univ School of Med
    • Louisiana
      • New Orleans、Louisiana、美国、70114
        • Louisiana Research Associates
    • Mississippi
      • Hattiesburg、Mississippi、美国、39401
        • Hattiesburg Clinic
    • Missouri
      • Saint Louis、Missouri、美国、63132
        • Millennium Psychiatric Associates, LLC
    • Nevada
      • Las Vegas、Nevada、美国、89106
        • Cleveland Clinic Lou Ruvo; Center for Brain Research
    • New Jersey
      • Eatontown、New Jersey、美国、07724
        • Memory Enhancement Center of America, Inc.
      • Mount Arlington、New Jersey、美国、07856
        • NeuroCognitive Institute
    • New York
      • Latham、New York、美国、12210
        • Empire Neurology, PC
      • Manhasset、New York、美国、11030
        • Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
      • New York、New York、美国、10032
        • Columbia University Medical Center
      • Rochester、New York、美国、14627
        • University of Rochester Medical Center; Monroe Community Hospital
      • Rochester、New York、美国、14642
        • Investigational Drug Service; Univ of Rochester Medical Ctr
    • North Carolina
      • Raleigh、North Carolina、美国、27607-6520
        • Raleigh Neurology Associates
    • Oregon
      • Portland、Oregon、美国、97210
        • Summit Research Network Inc.
    • Pennsylvania
      • Jenkintown、Pennsylvania、美国、19046
        • The Clinical Trial Center, LLC
    • Rhode Island
      • East Providence、Rhode Island、美国、02914
        • Rhode Island Mood & Memory Research Institute
      • Providence、Rhode Island、美国、02906
        • Butler Hospital
    • South Carolina
      • North Charleston、South Carolina、美国、29425
        • Medical Uni of South Carolina
    • Texas
      • Houston、Texas、美国、77030
        • Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
    • Vermont
      • Bennington、Vermont、美国、05201
        • Clinical Neuroscience Research Associates, Inc.
  • 英国
      • Bath、英国、BA1 3NG
        • The Rice Centre; Royal United Hospital
      • Brentford、英国、TW8 8DS
        • West London Research Unit; Brentford Lodge
      • Brighton、英国、BN2 5BE
        • Royal Sussex County Hospital, CIRU Level 5
      • Glasgow、英国、G20 0XA
        • Glasgow Memory Clinic
      • London, GT LON、英国、WC1N 3BG
        • The National Hospital for Neurology & Neurosurgery; Dementia Research Center
      • Southampton、英国、SO30 3JB
        • Moorgreen Hospital; Memory Assessment & Rsch Ctr
      • Southampton、英国、SO16 6YD
        • Southampton General Hospital; Pharmacy
      • Swindon、英国、SN3 6BW
        • Great Western Hosp.; Kingshill Research Ctr
  • 西班牙
      • Albacete、西班牙、2006
        • Complejo Hospitalario Universitario de Albacete
      • Madrid、西班牙、28006
        • Clinica Ruber, 4 planta; Servicio de Neurologia
    • Barcelona
      • BArcelon、Barcelona、西班牙、08034
        • Fundació ACE
      • San Cugat Del Valles、Barcelona、西班牙、08195
        • Hospital General De Catalunya
    • Guipuzcoa
      • San Sebastian、Guipuzcoa、西班牙、20009
        • Policlínica Guipuzcoa
    • Vizcaya
      • Barakaldo、Vizcaya、西班牙、48903
        • Hospital de Cruces; Servicio de Neurologia

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

50年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Previous participation in Study ABE4869g or ABE4955g and completion of the Week 73 visit
  • Adequate visual and auditory acuity, in the investigator's judgment, to allow for neuropsychological testing
  • Availability of a person ("caregiver") who can provide information on activities of daily living and behavior in order to complete the study-specific assessments
  • Diagnosis of probable Alzheimer's disease according to the National Institute on Neurological and Communication Disease and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (McKhann et al. 1984)
  • Mini-Mental State Examination (MMSE) score of 10 or more at screening (Folstein et al. 1975)
  • For male participants with partners with reproductive potential, agreement to use a reliable means of contraception (e.g., condoms) during the study and for at least 8 weeks following the last dose of study drug
  • For female participants, a negative pregnancy test at screening

Exclusion Criteria:

  • Early treatment and/or study discontinuation prior to completion of the Week 73 visit of Genentech Study ABE4869g or ABE4955g
  • Early discontinuation from the treatment schedule of a prior version of Study GN28525 for safety reasons. If treatment discontinuation occurred for safety reasons, participants may not re-start dosing on extended treatment schedules offered in amendments to Study GN28525
  • Inability to tolerate Magnetic Resonance Imaging (MRI) procedures or contraindication to MRI
  • Female participants with reproductive potential: Female participants must either have undergone documented surgical sterilization or have not experienced menstruation for at least 12 consecutive months
  • Severe or unstable medical condition that, in the opinion of the investigator or Sponsor, would interfere with the participant's ability to complete the study assessments or would require the equivalent of institutional or hospital care
  • History or presence of clinically evident vascular disease potentially affecting the brain
  • History of severe, clinically significant central nervous system trauma
  • History or presence of clinically relevant intracranial tumor
  • Presence of infections that affect the brain function or history of infections that resulted in neurologic sequelae
  • History or presence of systemic autoimmune disorders potentially causing progressive neurologic disease
  • History or presence of a neurologic disease other than Alzheimer's disease that may affect cognition
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
  • Evidence of malignancies (except squamous cell cancer or basal cell cancer of the skin), acute infections, renal failure that requires dialysis, or other unstable medical disease not related to Alzheimer's disease that, in the investigator's opinion, would preclude participant's participation. Cancer that is not being actively treated with anti-cancer therapy or radiotherapy as well as cancers which are considered to have low probability of recurrence are allowed
  • History or presence of atrial fibrillation that, in the investigator's judgment, poses a risk for future stroke
  • Chronic kidney disease of Stage greater than or equal to (>=) 4, according to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines for chronic kidney disease (CKD)
  • Impaired hepatic function
  • Impaired coagulation (activated partial thromboplastin time [aPTT] greater than [>] 1.2 times upper limit of normal [ULN])
  • Platelet count less than (<) 100,000 per microliter (mcL)
  • Presence at screening of superficial siderosis of central nervous system, more than 8 cerebral microhemorrhages, or evidence of a prior cerebral macrohemorrhage
  • Presence at screening of any other significant cerebral abnormalities, including ARIA-E
  • Treatment with anticoagulation medications within 2 weeks prior to enrollment. Clopidogrel, dipyridamole, and aspirin are permitted
  • Treatment with anticholinergic antidepressants, typical antipsychotics, or barbiturates within 2 weeks prior to enrollment. All other antidepressants and atypical antipsychotics are allowed with certain restrictions as defined in the protocol
  • Chronic use of opiates, opioids, or benzodiazepines
  • Any biologic therapy within 75 weeks prior to enrollment
  • Any investigational agent (other than crenezumab) within 75 weeks prior to enrollment
  • Treatment with anticholinergic antidepressants, typical antipsychotics, barbiturates, or narcotics within 5 half-lives or 3 months prior to screening, whichever is longer. All other antidepressants and atypical antipsychotics are allowed. Chronic use of benzodiazepines is not allowed; however, the intermittent use of benzodiazepines is allowed, except within 2 days prior to any neurocognitive assessment

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
药品：Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
其他名称：
  • RO5490245

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Percentage of Participants With Adverse Events (AEs)
大体时间：Up to 50 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product which does not necessarily 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. Preexisting conditions which worsen during a study are also considered as adverse events.
Up to 50 months
Percentage of Participants by Nature of AEs
大体时间：Up to 50 months
A serious adverse event (SAE) is any AE that meets any of the following criteria: fatal, life threatening, requires or prolongs inpatient hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect in a neonate/infant. Non-SAE of special interest for this study include the following: cerebral vascular edema, Superficial siderosis of central nervous system, cerebral micro-hemorrhages or macro-hemorrhages, pneumonia, liver injury.
Up to 50 months
Percentage of Participants by Severity of AEs
大体时间：Up to 50 months
AE severity grading scale for the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 was used for assessing adverse event severity. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1) mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2) moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL), Grade 3) severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4) life-threatening consequences; urgent intervention indicated, Grade 5) death related to AE.
Up to 50 months
Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation
大体时间：Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
ATA is a measurement to explore the potential relationship of immunogenicity response with pharmacokinetics, safety and efficacy. Percentage of participants at post-baseline with positive results for ATA against crenezumab are reported.
Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)
大体时间：Baseline, Weeks 23, 47, 71, 97, 121 and 153
Alzheimer's disease (AD) is associated with ARIA. The occurrence of imaging abnormalities believed to represent cerebral vasogenic edema, has been reported in association with the investigational use of compounds that are intended to treat Alzheimer's disease by reducing Abeta in the brain. Here, the percentage of participants with symptomatic and asymptomatic ARIA-E were reported.
Baseline, Weeks 23, 47, 71, 97, 121 and 153
Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)
大体时间：Baseline, Weeks 23, 47, 71, 97, 121 and 153
AD is associated with ARIA. Cerebral micro-hemorrhages (microbleeds [MBs]) are radiologically defined as small dot-like foci of signal loss observed on magnetic resonance imaging (MRI) sequences sensitive for paramagnetic tissue properties. The occurrence of MBs has also been identified as an adverse event in anti-amyloid vaccination trials, and together with superficial siderosis, they have been termed ARIA-H.
Baseline, Weeks 23, 47, 71, 97, 121 and 153

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Genentech, Inc.

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2012年12月7日

初级完成 (实际的)

2017年2月8日

研究完成 (实际的)

2017年2月8日

研究注册日期

首次提交

2012年11月6日

首先提交符合 QC 标准的

2012年11月6日

首次发布 (估计)

2012年11月8日

研究记录更新

最后更新发布 (实际的)

2020年2月20日

上次提交的符合 QC 标准的更新

2020年2月18日

最后验证

2020年2月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • GN28525
  • 2012-003242-33 (EudraCT编号)

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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