A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
18 de febrero de 2020 actualizado por: 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.
Descripción general del estudio
Tipo de estudio
Intervencionista
Inscripción (Actual)
360
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania, 12203
- Univ Berlin; Klin fur Psychi & Psycho Charite
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Günzburg, Alemania, 89312
- Bezirkskrankenhaus Günzburg
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Mannheim, Alemania, 68159
- Zentralinstitut fuer Seelische Gesundheit
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Munchen, Alemania, 81377
- Ludwig-Maximilians-Univ.
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Munchen, Alemania, 81675
- Klinikum rechts der Isar der Technischen Universität München
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Tubingen, Alemania, 72076
- Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
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British Columbia
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Kelowna, British Columbia, Canadá, V1Y 3G8
- The Med Arts Health Rsrch Grp
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Vancouver, British Columbia, Canadá, V6T 2B5
- University of British Columbia Hospital; Division of Neurology
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Nova Scotia
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Halilfax, Nova Scotia, Canadá, B3H 2E1
- Capitol District Health Authority
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Ontario
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Burlington, Ontario, Canadá, L7M 4Y1
- JBN Medical Diagnostic Services Inc.
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Kingston, Ontario, Canadá, K7L 2V7
- Hotel Dieu Hospital
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London, Ontario, Canadá, N6C 5J1
- St. Joseph's HC-Parkwood Hosp
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Ottawa, Ontario, Canadá, K1N 5C8
- Bruyere Continuing Care
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Peterborough, Ontario, Canadá, K9H 2P4
- Kawartha Centre - Redefining Healthy Aging
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Toronto, Ontario, Canadá, M3B 2S7
- Toronto Memory Program (Neurology Research Inc.)
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Quebec
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Greenfield Park, Quebec, Canadá, J4V 2J2
- Clinique Neuro Rive-Sud
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Montreal, Quebec, Canadá, H1T 2M4
- Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique
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Quebec City, Quebec, Canadá, G1J 1Z4
- CHAUQ Hopital Enfant-Jesus
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Verdun, Quebec, Canadá, H4H 1R3
- McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
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Albacete, España, 2006
- Complejo Hospitalario Universitario de Albacete
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Madrid, España, 28006
- Clinica Ruber, 4 planta; Servicio de Neurologia
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Barcelona
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BArcelon, Barcelona, España, 08034
- Fundació ACE
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San Cugat Del Valles, Barcelona, España, 08195
- Hospital General De Catalunya
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Guipuzcoa
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San Sebastian, Guipuzcoa, España, 20009
- Policlínica Guipuzcoa
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Vizcaya
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Barakaldo, Vizcaya, España, 48903
- Hospital de Cruces; Servicio de Neurologia
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Arizona
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Phoenix, Arizona, Estados Unidos, 85006
- Banner Alzheimer's Institute
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Scottsdale, Arizona, Estados Unidos, 85259
- Mayo Clinic
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Sun City, Arizona, Estados Unidos, 85351
- Banner Sun Health Research Insitute
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California
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Encino, California, Estados Unidos, 91316
- Pharmacology Research Inst
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Fresno, California, Estados Unidos, 93720
- Margolin Brain Institute
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La Jolla, California, Estados Unidos, 92037
- Univ of CA San Diego; Neurosciences Comp.Alzheimer's
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Los Angeles, California, Estados Unidos, 90095
- University of California Los Angeles (UCLA)
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Los Angeles, California, Estados Unidos, 90033
- USC School of Medicine
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Newport Beach, California, Estados Unidos, 92660
- Pharmacology Research Inst
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Oxnard, California, Estados Unidos, 93030
- Pacific Neuroscience Med Grp
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Palo Alto, California, Estados Unidos, 94304
- Stanford Univ Medical Center
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Sacramento, California, Estados Unidos, 95817
- University of California Davis Medical System
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San Diego, California, Estados Unidos, 92103
- Pacific Research Network - PRN
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San Francisco, California, Estados Unidos, 94117
- Uni of California San Francisco
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Santa Rosa, California, Estados Unidos, 95403
- Redwood Regional Medical Group
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06511
- Yale University
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Florida
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Boca Raton, Florida, Estados Unidos, 33431
- Florida Atlantic University; College of Medicine
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Brooksville, Florida, Estados Unidos, 34601
- Meridien Research
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Delray Beach, Florida, Estados Unidos, 33445
- Brain Matters Research, Inc.
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Miami, Florida, Estados Unidos, 33137
- Miami Jewish Health Systems; Clinical Research
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Naples, Florida, Estados Unidos, 34105
- Collier Neurologic Specialists
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Orlando, Florida, Estados Unidos, 32806
- Bioclinica Research
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Tampa, Florida, Estados Unidos, 33609
- Axiom Clinical Research of Florida
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West Palm Beach, Florida, Estados Unidos, 33407
- Premiere Research Institute
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Georgia
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Decatur, Georgia, Estados Unidos, 30033
- DeKalb Neurology Associates
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Illinois
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Chicago, Illinois, Estados Unidos, 60612
- Rush Alzheimer's Disease Cntr.
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Elk Grove Village, Illinois, Estados Unidos, 60007
- Alexian Brothers Neurosci Inst
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46202
- Indiana Univ School of Med
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Louisiana
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New Orleans, Louisiana, Estados Unidos, 70114
- Louisiana Research Associates
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Mississippi
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Hattiesburg, Mississippi, Estados Unidos, 39401
- Hattiesburg Clinic
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Missouri
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Saint Louis, Missouri, Estados Unidos, 63132
- Millennium Psychiatric Associates, LLC
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Nevada
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Las Vegas, Nevada, Estados Unidos, 89106
- Cleveland Clinic Lou Ruvo; Center for Brain Research
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New Jersey
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Eatontown, New Jersey, Estados Unidos, 07724
- Memory Enhancement Center of America, Inc.
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Mount Arlington, New Jersey, Estados Unidos, 07856
- NeuroCognitive Institute
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New York
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Latham, New York, Estados Unidos, 12210
- Empire Neurology, PC
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Manhasset, New York, Estados Unidos, 11030
- Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
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New York, New York, Estados Unidos, 10032
- Columbia University Medical Center
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Rochester, New York, Estados Unidos, 14627
- University of Rochester Medical Center; Monroe Community Hospital
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Rochester, New York, Estados Unidos, 14642
- Investigational Drug Service; Univ of Rochester Medical Ctr
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North Carolina
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Raleigh, North Carolina, Estados Unidos, 27607-6520
- Raleigh Neurology Associates
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Oregon
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Portland, Oregon, Estados Unidos, 97210
- Summit Research Network Inc.
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Pennsylvania
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Jenkintown, Pennsylvania, Estados Unidos, 19046
- The Clinical Trial Center, LLC
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Rhode Island
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East Providence, Rhode Island, Estados Unidos, 02914
- Rhode Island Mood & Memory Research Institute
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Providence, Rhode Island, Estados Unidos, 02906
- Butler Hospital
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South Carolina
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North Charleston, South Carolina, Estados Unidos, 29425
- Medical Uni of South Carolina
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Texas
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Houston, Texas, Estados Unidos, 77030
- Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
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Vermont
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Bennington, Vermont, Estados Unidos, 05201
- Clinical Neuroscience Research Associates, Inc.
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Bron, Francia, 69677
- Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
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Limoges, Francia, 87042
- CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
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Nancy, Francia, 54035
- Hopital Central; Neurologie
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Nantes, Francia, 44093
- Hôpital Nord Laennec
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Rouen, Francia, 76031
- CHU de Rouen Hopital; Service de Neurologie
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Strasbourg, Francia, 67091
- Hôpital Civil de Strasbourg
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Bath, Reino Unido, BA1 3NG
- The Rice Centre; Royal United Hospital
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Brentford, Reino Unido, TW8 8DS
- West London Research Unit; Brentford Lodge
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Brighton, Reino Unido, BN2 5BE
- Royal Sussex County Hospital, CIRU Level 5
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Glasgow, Reino Unido, G20 0XA
- Glasgow Memory Clinic
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London, GT LON, Reino Unido, WC1N 3BG
- The National Hospital for Neurology & Neurosurgery; Dementia Research Center
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Southampton, Reino Unido, SO30 3JB
- Moorgreen Hospital; Memory Assessment & Rsch Ctr
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Southampton, Reino Unido, SO16 6YD
- Southampton General Hospital; Pharmacy
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Swindon, Reino Unido, SN3 6BW
- Great Western Hosp.; Kingshill Research Ctr
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
50 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
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Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percentage of Participants With Adverse Events (AEs)
Periodo de tiempo: Up to 50 months
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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.
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Up to 50 months
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Percentage of Participants by Nature of AEs
Periodo de tiempo: Up to 50 months
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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.
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Up to 50 months
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Percentage of Participants by Severity of AEs
Periodo de tiempo: Up to 50 months
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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.
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Up to 50 months
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Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation
Periodo de tiempo: Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
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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.
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Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
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Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)
Periodo de tiempo: Baseline, Weeks 23, 47, 71, 97, 121 and 153
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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.
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Baseline, Weeks 23, 47, 71, 97, 121 and 153
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Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)
Periodo de tiempo: Baseline, Weeks 23, 47, 71, 97, 121 and 153
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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.
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Baseline, Weeks 23, 47, 71, 97, 121 and 153
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
7 de diciembre de 2012
Finalización primaria (Actual)
8 de febrero de 2017
Finalización del estudio (Actual)
8 de febrero de 2017
Fechas de registro del estudio
Enviado por primera vez
6 de noviembre de 2012
Primero enviado que cumplió con los criterios de control de calidad
6 de noviembre de 2012
Publicado por primera vez (Estimar)
8 de noviembre de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
20 de febrero de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
18 de febrero de 2020
Última verificación
1 de febrero de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GN28525
- 2012-003242-33 (Número EudraCT)
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Sí
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .