Clinical trial NCT01723826: A Long-Term Safety Extension of Studies ABE4869g and ABE4955g in Participants With Mild to Moderate Alzheimer's Disease Treated With Crenezumab
Official title: A Multicenter, Open-Label, Long-Term Safety Extension of Phase II Studies ABE4869g and ABE4955g in Patients With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-11-08
Enrollment: 360
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: Up to 50 months
measure: Percentage of Participants by Nature of AEs
timeFrame: Up to 50 months
measure: Percentage of Participants by Severity of AEs
timeFrame: Up to 50 months
measure: Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation
timeFrame: Pre-dose (Day-14), predose at Week 25, 49, 97, Follow-up Week 8 (Week 153) and 12 (Week 157)
measure: Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)
timeFrame: Baseline, Weeks 23, 47, 71, 97, 121 and 153
measure: Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)
timeFrame: Baseline, Weeks 23, 47, 71, 97, 121 and 153
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health Research Insitute
state: Arizona
city: Encino
country: United States
facility: Pharmacology Research Inst
state: California
city: Fresno
country: United States
facility: Margolin Brain Institute
state: California
city: La Jolla
country: United States
facility: Univ of CA San Diego; Neurosciences Comp.Alzheimer's
state: California
city: Los Angeles
country: United States
facility: USC School of Medicine
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Newport Beach
country: United States
facility: Pharmacology Research Inst
state: California
city: Oxnard
country: United States
facility: Pacific Neuroscience Med Grp
state: California
city: Palo Alto
country: United States
facility: Stanford Univ Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical System
state: California
city: San Diego
country: United States
facility: Pacific Research Network - PRN
state: California
city: San Francisco
country: United States
facility: Uni of California San Francisco
state: California
city: Santa Rosa
country: United States
facility: Redwood Regional Medical Group
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Boca Raton
country: United States
facility: Florida Atlantic University; College of Medicine
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research, Inc.
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems; Clinical Research
state: Florida
city: Naples
country: United States
facility: Collier Neurologic Specialists
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Decatur
country: United States
facility: Dekalb Neurology Associates
state: Georgia
city: Chicago
country: United States
facility: Rush Alzheimer's Disease Cntr.
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosci Inst
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ School of Med
state: Indiana
city: New Orleans
country: United States
facility: Louisiana Research Associates
state: Louisiana
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic
state: Mississippi
city: Saint Louis
country: United States
facility: Millennium Psychiatric Associates, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo; Center for Brain Research
state: Nevada
city: Eatontown
country: United States
facility: Memory Enhancement Center of America, Inc.
state: New Jersey
city: Mount Arlington
country: United States
facility: NeuroCognitive Institute
state: New Jersey
city: Latham
country: United States
facility: Empire Neurology, PC
state: New York
city: Manhasset
country: United States
facility: Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center; Monroe Community Hospital
state: New York
city: Rochester
country: United States
facility: Investigational Drug Service; Univ of Rochester Medical Ctr
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Portland
country: United States
facility: Summit Research Network Inc.
state: Oregon
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: East Providence
country: United States
facility: Rhode Island Mood & Memory Research Institute
state: Rhode Island
city: Providence
country: United States
facility: Butler Hospital
state: Rhode Island
city: North Charleston
country: United States
facility: Medical Uni of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine
state: Texas
city: Bennington
country: United States
facility: Clinical Neuroscience Research Associates, Inc.
state: Vermont
city: Kelowna
country: Canada
facility: The Med Arts Health Rsrch Grp
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia Hospital; Division of Neurology
state: British Columbia
city: Halilfax
country: Canada
facility: Capitol District Health Authority
state: Nova Scotia
city: Burlington
country: Canada
facility: Jbn Medical Diagnostic Services Inc.
state: Ontario
city: Kingston
country: Canada
facility: Hotel Dieu Hospital
state: Ontario
city: London
country: Canada
facility: St. Joseph's HC-Parkwood Hosp
state: Ontario
city: Ottawa
country: Canada
facility: Bruyere Continuing Care
state: Ontario
city: Peterborough
country: Canada
facility: Kawartha Centre - Redefining Healthy Aging
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program (Neurology Research Inc.)
state: Ontario
city: Greenfield Park
country: Canada
facility: Clinique Neuro Rive-Sud
state: Quebec
city: Montreal
country: Canada
facility: Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique
state: Quebec
city: Quebec City
country: Canada
facility: CHAUQ Hopital Enfant-Jesus
state: Quebec
city: Verdun
country: Canada
facility: McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric
state: Quebec
city: Bron
country: France
facility: Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie
city: Limoges
country: France
facility: CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique
city: Nancy
country: France
facility: Hopital Central; Neurologie
city: Nantes
country: France
facility: Hopital Nord Laennec
city: Rouen
country: France
facility: CHU de Rouen Hopital; Service de Neurologie
city: Strasbourg
country: France
facility: Hôpital Civil de Strasbourg
city: Berlin
country: Germany
facility: Univ Berlin; Klin fur Psychi & Psycho Charite
city: Günzburg
country: Germany
facility: Bezirkskrankenhaus Günzburg
city: Mannheim
country: Germany
facility: Zentralinstitut fuer Seelische Gesundheit
city: Munchen
country: Germany
facility: Ludwig-Maximilians-Univ.
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universität München
city: Tubingen
country: Germany
facility: Universitätsklinik Tübingen; Psychiatrie und Psychotherapie
city: BArcelon
country: Spain
facility: Fundació ACE
state: Barcelona
city: San Cugat Del Valles
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: San Sebastian
country: Spain
facility: Policlinica Guipuzcoa
state: Guipuzcoa
city: Barakaldo
country: Spain
facility: Hospital de Cruces; Servicio de Neurologia
state: Vizcaya
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete
city: Madrid
country: Spain
facility: Clinica Ruber, 4 planta; Servicio de Neurologia
city: Bath
country: United Kingdom
facility: The Rice Centre; Royal United Hospital
city: Brentford
country: United Kingdom
facility: West London Research Unit; Brentford Lodge
city: Brighton
country: United Kingdom
facility: Royal Sussex County Hospital, CIRU Level 5
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic
city: London, GT LON
country: United Kingdom
facility: The National Hospital for Neurology & Neurosurgery; Dementia Research Center
city: Southampton
country: United Kingdom
facility: Southampton General Hospital; Pharmacy
city: Southampton
country: United Kingdom
facility: Moorgreen Hospital; Memory Assessment & Rsch Ctr
city: Swindon
country: United Kingdom
facility: Great Western Hosp.; Kingshill Research Ctr
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: