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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01723826
• Other study ID #: GN28525
• Secondary ID: 2012-003242-33
• Status: Completed
• Phase: Phase 2
• Start date: December 7, 2012
• Est. completion date: February 8, 2017

Study information

• Verified date: February 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: February 8, 2017
• Est. primary completion date: February 8, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• Crenezumab
Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Adverse Events (AEs)	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
Primary	Percentage of Participants by Nature of AEs	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
Primary	Percentage of Participants by Severity of AEs	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
Primary	Percentage of Participants With Human Anti-Therapeutic Antibody (ATA) Formation	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)
Primary	Percentage of Participants With Amyloid-Related Imaging Abnormalities Edema/Effusions (ARIA-E)	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
Primary	Percentage of Participants With Amyloid-Related Imaging Abnormalities-Hemorrhage (ARIA-H)	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