A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
18. februar 2020 oppdatert av: 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.
Studieoversikt
Studietype
Intervensjonell
Registrering (Faktiske)
360
Fase
- Fase 2
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
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British Columbia
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Kelowna, British Columbia, Canada, V1Y 3G8
- The Med Arts Health Rsrch Grp
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Vancouver, British Columbia, Canada, V6T 2B5
- University of British Columbia Hospital; Division of Neurology
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Nova Scotia
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Halilfax, Nova Scotia, Canada, B3H 2E1
- Capitol District Health Authority
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Ontario
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Burlington, Ontario, Canada, L7M 4Y1
- JBN Medical Diagnostic Services Inc.
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Kingston, Ontario, Canada, K7L 2V7
- Hotel Dieu Hospital
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London, Ontario, Canada, N6C 5J1
- St. Joseph's HC-Parkwood Hosp
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Ottawa, Ontario, Canada, K1N 5C8
- Bruyere Continuing Care
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Peterborough, Ontario, Canada, K9H 2P4
- Kawartha Centre - Redefining Healthy Aging
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Toronto, Ontario, Canada, M3B 2S7
- Toronto Memory Program (Neurology Research Inc.)
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Quebec
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Greenfield Park, Quebec, Canada, J4V 2J2
- Clinique Neuro Rive-Sud
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Montreal, Quebec, Canada, H1T 2M4
- Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique
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Quebec City, Quebec, Canada, G1J 1Z4
- CHAUQ Hopital Enfant-Jesus
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Verdun, Quebec, Canada, H4H 1R3
- McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
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Arizona
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Phoenix, Arizona, Forente stater, 85006
- Banner Alzheimer's Institute
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Scottsdale, Arizona, Forente stater, 85259
- Mayo Clinic
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Sun City, Arizona, Forente stater, 85351
- Banner Sun Health Research Insitute
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California
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Encino, California, Forente stater, 91316
- Pharmacology Research Inst
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Fresno, California, Forente stater, 93720
- Margolin Brain Institute
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La Jolla, California, Forente stater, 92037
- Univ of CA San Diego; Neurosciences Comp.Alzheimer's
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Los Angeles, California, Forente stater, 90095
- University of California Los Angeles (UCLA)
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Los Angeles, California, Forente stater, 90033
- USC School of Medicine
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Newport Beach, California, Forente stater, 92660
- Pharmacology Research Inst
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Oxnard, California, Forente stater, 93030
- Pacific Neuroscience Med Grp
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Palo Alto, California, Forente stater, 94304
- Stanford Univ Medical Center
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Sacramento, California, Forente stater, 95817
- University of California Davis Medical System
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San Diego, California, Forente stater, 92103
- Pacific Research Network - PRN
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San Francisco, California, Forente stater, 94117
- Uni of California San Francisco
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Santa Rosa, California, Forente stater, 95403
- Redwood Regional Medical Group
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Connecticut
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New Haven, Connecticut, Forente stater, 06511
- Yale University
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Florida
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Boca Raton, Florida, Forente stater, 33431
- Florida Atlantic University; College of Medicine
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Brooksville, Florida, Forente stater, 34601
- Meridien Research
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Delray Beach, Florida, Forente stater, 33445
- Brain Matters Research, Inc.
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Miami, Florida, Forente stater, 33137
- Miami Jewish Health Systems; Clinical Research
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Naples, Florida, Forente stater, 34105
- Collier Neurologic Specialists
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Orlando, Florida, Forente stater, 32806
- Bioclinica Research
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Tampa, Florida, Forente stater, 33609
- Axiom Clinical Research of Florida
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West Palm Beach, Florida, Forente stater, 33407
- Premiere Research Institute
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Georgia
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Decatur, Georgia, Forente stater, 30033
- DeKalb Neurology Associates
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Illinois
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Chicago, Illinois, Forente stater, 60612
- Rush Alzheimer's Disease Cntr.
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Elk Grove Village, Illinois, Forente stater, 60007
- Alexian Brothers Neurosci Inst
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Indiana
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Indianapolis, Indiana, Forente stater, 46202
- Indiana Univ School of Med
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Louisiana
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New Orleans, Louisiana, Forente stater, 70114
- Louisiana Research Associates
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Mississippi
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Hattiesburg, Mississippi, Forente stater, 39401
- Hattiesburg Clinic
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Missouri
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Saint Louis, Missouri, Forente stater, 63132
- Millennium Psychiatric Associates, LLC
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Nevada
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Las Vegas, Nevada, Forente stater, 89106
- Cleveland Clinic Lou Ruvo; Center for Brain Research
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New Jersey
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Eatontown, New Jersey, Forente stater, 07724
- Memory Enhancement Center of America, Inc.
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Mount Arlington, New Jersey, Forente stater, 07856
- NeuroCognitive Institute
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New York
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Latham, New York, Forente stater, 12210
- Empire Neurology, PC
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Manhasset, New York, Forente stater, 11030
- Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
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New York, New York, Forente stater, 10032
- Columbia University Medical Center
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Rochester, New York, Forente stater, 14627
- University of Rochester Medical Center; Monroe Community Hospital
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Rochester, New York, Forente stater, 14642
- Investigational Drug Service; Univ of Rochester Medical Ctr
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North Carolina
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Raleigh, North Carolina, Forente stater, 27607-6520
- Raleigh Neurology Associates
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Oregon
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Portland, Oregon, Forente stater, 97210
- Summit Research Network Inc.
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Pennsylvania
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Jenkintown, Pennsylvania, Forente stater, 19046
- The Clinical Trial Center, LLC
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Rhode Island
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East Providence, Rhode Island, Forente stater, 02914
- Rhode Island Mood & Memory Research Institute
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Providence, Rhode Island, Forente stater, 02906
- Butler Hospital
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South Carolina
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North Charleston, South Carolina, Forente stater, 29425
- Medical Uni of South Carolina
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Texas
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Houston, Texas, Forente stater, 77030
- Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
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Vermont
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Bennington, Vermont, Forente stater, 05201
- Clinical Neuroscience Research Associates, Inc.
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Bron, Frankrike, 69677
- Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
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Limoges, Frankrike, 87042
- CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
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Nancy, Frankrike, 54035
- Hopital Central; Neurologie
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Nantes, Frankrike, 44093
- Hôpital Nord Laennec
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Rouen, Frankrike, 76031
- CHU de Rouen Hopital; Service de Neurologie
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Strasbourg, Frankrike, 67091
- Hôpital Civil de Strasbourg
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Albacete, Spania, 2006
- Complejo Hospitalario Universitario de Albacete
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Madrid, Spania, 28006
- Clinica Ruber, 4 planta; Servicio de Neurologia
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Barcelona
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BArcelon, Barcelona, Spania, 08034
- Fundació ACE
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San Cugat Del Valles, Barcelona, Spania, 08195
- Hospital General De Catalunya
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Guipuzcoa
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San Sebastian, Guipuzcoa, Spania, 20009
- Policlínica Guipuzcoa
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Vizcaya
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Barakaldo, Vizcaya, Spania, 48903
- Hospital de Cruces; Servicio de Neurologia
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Bath, Storbritannia, BA1 3NG
- The Rice Centre; Royal United Hospital
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Brentford, Storbritannia, TW8 8DS
- West London Research Unit; Brentford Lodge
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Brighton, Storbritannia, BN2 5BE
- Royal Sussex County Hospital, CIRU Level 5
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Glasgow, Storbritannia, G20 0XA
- Glasgow Memory Clinic
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London, GT LON, Storbritannia, WC1N 3BG
- The National Hospital for Neurology & Neurosurgery; Dementia Research Center
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Southampton, Storbritannia, SO30 3JB
- Moorgreen Hospital; Memory Assessment & Rsch Ctr
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Southampton, Storbritannia, SO16 6YD
- Southampton General Hospital; Pharmacy
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Swindon, Storbritannia, SN3 6BW
- Great Western Hosp.; Kingshill Research Ctr
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Berlin, Tyskland, 12203
- Univ Berlin; Klin fur Psychi & Psycho Charite
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Günzburg, Tyskland, 89312
- Bezirkskrankenhaus Günzburg
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Mannheim, Tyskland, 68159
- Zentralinstitut fuer Seelische Gesundheit
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Munchen, Tyskland, 81377
- Ludwig-Maximilians-Univ.
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Munchen, Tyskland, 81675
- Klinikum rechts der Isar der Technischen Universität München
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Tubingen, Tyskland, 72076
- Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
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Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
50 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Nei
Kjønn som er kvalifisert for studier
Alle
Beskrivelse
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
Studieplan
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: 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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Percentage of Participants With Adverse Events (AEs)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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.
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Baseline, Weeks 23, 47, 71, 97, 121 and 153
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Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Sponsor
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
7. desember 2012
Primær fullføring (Faktiske)
8. februar 2017
Studiet fullført (Faktiske)
8. februar 2017
Datoer for studieregistrering
Først innsendt
6. november 2012
Først innsendt som oppfylte QC-kriteriene
6. november 2012
Først lagt ut (Anslag)
8. november 2012
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
20. februar 2020
Siste oppdatering sendt inn som oppfylte QC-kriteriene
18. februar 2020
Sist bekreftet
1. februar 2020
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- GN28525
- 2012-003242-33 (EudraCT-nummer)
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .