A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
- Registration Number
- NCT01723826
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 360
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Crenezumab Crenezumab Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation 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.
Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H) 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.
Percentage of Participants With Adverse Events (AEs) 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.
Percentage of Participants by Nature of AEs 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.
Percentage of Participants by Severity of AEs 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.
Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E) 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (85)
Toronto Memory Program (Neurology Research Inc.)
🇨🇦Toronto, Ontario, Canada
University of California Los Angeles (UCLA)
🇺🇸Los Angeles, California, United States
Margolin Brain Institute
🇺🇸Fresno, California, United States
Raleigh Neurology Associates
🇺🇸Raleigh, North Carolina, United States
NeuroCognitive Institute
🇺🇸Mount Arlington, New Jersey, United States
University of Rochester Medical Center; Monroe Community Hospital
🇺🇸Rochester, New York, United States
Southampton General Hospital; Pharmacy
🇬🇧Southampton, United Kingdom
Pacific Research Network - PRN
🇺🇸San Diego, California, United States
Cleveland Clinic Lou Ruvo; Center for Brain Research
🇺🇸Las Vegas, Nevada, United States
Rush Alzheimer's Disease Cntr.
🇺🇸Chicago, Illinois, United States
Indiana Univ School of Med
🇺🇸Indianapolis, Indiana, United States
Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
🇺🇸Houston, Texas, United States
Uni of California San Francisco
🇺🇸San Francisco, California, United States
Florida Atlantic University; College of Medicine
🇺🇸Boca Raton, Florida, United States
Hotel Dieu Hospital
🇨🇦Kingston, Ontario, Canada
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
Clinical Neuroscience Research Associates, Inc.
🇺🇸Bennington, Vermont, United States
Banner Sun Health Research Insitute
🇺🇸Sun City, Arizona, United States
Collier Neurologic Specialists
🇺🇸Naples, Florida, United States
Miami Jewish Health Systems; Clinical Research
🇺🇸Miami, Florida, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
Meridien Research
🇺🇸Brooksville, Florida, United States
Bioclinica Research
🇺🇸Orlando, Florida, United States
Brain Matters Research, Inc.
🇺🇸Delray Beach, Florida, United States
McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
🇨🇦Verdun, Quebec, Canada
Hôpital Civil de Strasbourg
🇫🇷Strasbourg, France
Ludwig-Maximilians-Univ.
🇩🇪Munchen, Germany
Hospital General de Catalunya
🇪🇸San Cugat Del Valles, Barcelona, Spain
Medical Uni of South Carolina
🇺🇸North Charleston, South Carolina, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
Jbn Medical Diagnostic Services Inc.
🇨🇦Burlington, Ontario, Canada
Premiere Research Institute
🇺🇸West Palm Beach, Florida, United States
Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
🇫🇷Bron, France
Bezirkskrankenhaus Günzburg
🇩🇪Günzburg, Germany
Kawartha Centre - Redefining Healthy Aging
🇨🇦Peterborough, Ontario, Canada
CHAUQ Hopital Enfant-Jesus
🇨🇦Quebec City, Quebec, Canada
Klinikum rechts der Isar der Technischen Universität München
🇩🇪Munchen, Germany
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
University of British Columbia Hospital; Division of Neurology
🇨🇦Vancouver, British Columbia, Canada
Bruyere Continuing Care
🇨🇦Ottawa, Ontario, Canada
Capitol District Health Authority
🇨🇦Halilfax, Nova Scotia, Canada
Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique
🇨🇦Montreal, Quebec, Canada
CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
🇫🇷Limoges, France
Hopital Central; Neurologie
🇫🇷Nancy, France
Hopital Nord Laennec
🇫🇷Nantes, France
CHU de Rouen Hopital; Service de Neurologie
🇫🇷Rouen, France
Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
🇩🇪Tubingen, Germany
The Med Arts Health Rsrch Grp
🇨🇦Kelowna, British Columbia, Canada
Clinique Neuro Rive-Sud
🇨🇦Greenfield Park, Quebec, Canada
Fundació ACE
🇪🇸BArcelon, Barcelona, Spain
Summit Research Network Inc.
🇺🇸Portland, Oregon, United States
Axiom Clinical Research of Florida
🇺🇸Tampa, Florida, United States
Univ Berlin; Klin fur Psychi & Psycho Charite
🇩🇪Berlin, Germany
Yale University
🇺🇸New Haven, Connecticut, United States
University of California Davis Medical System
🇺🇸Sacramento, California, United States
Pharmacology Research Inst
🇺🇸Newport Beach, California, United States
Univ of CA San Diego; Neurosciences Comp.Alzheimer's
🇺🇸La Jolla, California, United States
USC School of Medicine
🇺🇸Los Angeles, California, United States
Redwood Regional Medical Group
🇺🇸Santa Rosa, California, United States
Pacific Neuroscience Med Grp
🇺🇸Oxnard, California, United States
Stanford Univ Medical Center
🇺🇸Palo Alto, California, United States
Dekalb Neurology Associates
🇺🇸Decatur, Georgia, United States
Alexian Brothers Neurosci Inst
🇺🇸Elk Grove Village, Illinois, United States
Millennium Psychiatric Associates, LLC
🇺🇸Saint Louis, Missouri, United States
Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
🇺🇸Manhasset, New York, United States
Empire Neurology, PC
🇺🇸Latham, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Investigational Drug Service; Univ of Rochester Medical Ctr
🇺🇸Rochester, New York, United States
Butler Hospital
🇺🇸Providence, Rhode Island, United States
The Clinical Trial Center, LLC
🇺🇸Jenkintown, Pennsylvania, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
St. Joseph's HC-Parkwood Hosp
🇨🇦London, Ontario, Canada
Zentralinstitut fuer Seelische Gesundheit
🇩🇪Mannheim, Germany
Policlinica Guipuzcoa
🇪🇸San Sebastian, Guipuzcoa, Spain
Hospital de Cruces; Servicio de Neurologia
🇪🇸Barakaldo, Vizcaya, Spain
Complejo Hospitalario Universitario de Albacete
🇪🇸Albacete, Spain
Royal Sussex County Hospital, CIRU Level 5
🇬🇧Brighton, United Kingdom
The Rice Centre; Royal United Hospital
🇬🇧Bath, United Kingdom
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
West London Research Unit; Brentford Lodge
🇬🇧Brentford, United Kingdom
The National Hospital for Neurology & Neurosurgery; Dementia Research Center
🇬🇧London, GT LON, United Kingdom
Great Western Hosp.; Kingshill Research Ctr
🇬🇧Swindon, United Kingdom
Moorgreen Hospital; Memory Assessment & Rsch Ctr
🇬🇧Southampton, United Kingdom
Clinica Ruber, 4 planta; Servicio de Neurologia
🇪🇸Madrid, Spain
Louisiana Research Associates
🇺🇸New Orleans, Louisiana, United States