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

NCT01723826 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: GN285252012-003242-33
• Study Type: interventional
• Target: 360
• Locations: 6 countries
• Sites: 86

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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)

• 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

• 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

Study Arms (1)

Crenezumab

EXPERIMENTAL

Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.

Drug: Crenezumab

Interventions

Crenezumab DRUG

Participants will receive intravenous infusion of crenezumab every 4 weeks for 144 weeks.

Also known as: RO5490245

Crenezumab

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (86)

Banner Alzheimer's Institute

Phoenix, Arizona, 85006, United States

Location

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Banner Sun Health Research Insitute

Sun City, Arizona, 85351, United States

Location

Pharmacology Research Inst

Encino, California, 91316, United States

Location

Margolin Brain Institute

Fresno, California, 93720, United States

Location

Univ of CA San Diego; Neurosciences Comp.Alzheimer's

La Jolla, California, 92037, United States

Location

USC School of Medicine

Los Angeles, California, 90033, United States

Location

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

Location

Pharmacology Research Inst

Newport Beach, California, 92660, United States

Location

Pacific Neuroscience Med Grp

Oxnard, California, 93030, United States

Location

Stanford Univ Medical Center

Palo Alto, California, 94304, United States

Location

University of California Davis Medical System

Sacramento, California, 95817, United States

Location

Pacific Research Network - PRN

San Diego, California, 92103, United States

Location

Uni of California San Francisco

San Francisco, California, 94117, United States

Location

Redwood Regional Medical Group

Santa Rosa, California, 95403, United States

Location

Yale University

New Haven, Connecticut, 06511, United States

Location

Florida Atlantic University; College of Medicine

Boca Raton, Florida, 33431, United States

Location

Meridien Research

Brooksville, Florida, 34601, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Miami Jewish Health Systems; Clinical Research

Miami, Florida, 33137, United States

Location

Collier Neurologic Specialists

Naples, Florida, 34105, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Axiom Clinical Research of Florida

Tampa, Florida, 33609, United States

Location

Premiere Research Institute

West Palm Beach, Florida, 33407, United States

Location

Dekalb Neurology Associates

Decatur, Georgia, 30033, United States

Location

Rush Alzheimer's Disease Cntr.

Chicago, Illinois, 60612, United States

Location

Alexian Brothers Neurosci Inst

Elk Grove Village, Illinois, 60007, United States

Location

Indiana Univ School of Med

Indianapolis, Indiana, 46202, United States

Location

Louisiana Research Associates

New Orleans, Louisiana, 70114, United States

Location

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401, United States

Location

Millennium Psychiatric Associates, LLC

St Louis, Missouri, 63132, United States

Location

Cleveland Clinic Lou Ruvo; Center for Brain Research

Las Vegas, Nevada, 89106, United States

Location

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, 07724, United States

Location

NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Empire Neurology, PC

Latham, New York, 12210, United States

Location

Litwin Zucker Research Ctr.; Feinstein Inst. Med. Rsch.

Manhasset, New York, 11030, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center; Monroe Community Hospital

Rochester, New York, 14627, United States

Location

Investigational Drug Service; Univ of Rochester Medical Ctr

Rochester, New York, 14642, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607-6520, United States

Location

Summit Research Network Inc.

Portland, Oregon, 97210, United States

Location

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, 19046, United States

Location

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, 02914, United States

Location

Butler Hospital

Providence, Rhode Island, 02906, United States

Location

Medical Uni of South Carolina

North Charleston, South Carolina, 29425, United States

Location

Alzheimers Disease & Memory Disorders Center; Department of Neurology Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Clinical Neuroscience Research Associates, Inc.

Bennington, Vermont, 05201, United States

Location

The Med Arts Health Rsrch Grp

Kelowna, British Columbia, V1Y 3G8, Canada

Location

University of British Columbia Hospital; Division of Neurology

Vancouver, British Columbia, V6T 2B5, Canada

Location

Capitol District Health Authority

Halilfax, Nova Scotia, B3H 2E1, Canada

Location

Jbn Medical Diagnostic Services Inc.

Burlington, Ontario, L7M 4Y1, Canada

Location

Hotel Dieu Hospital

Kingston, Ontario, K7L 2V7, Canada

Location

St. Joseph's HC-Parkwood Hosp

London, Ontario, N6C 5J1, Canada

Location

Bruyere Continuing Care

Ottawa, Ontario, K1N 5C8, Canada

Location

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, K9H 2P4, Canada

Location

Toronto Memory Program (Neurology Research Inc.)

Toronto, Ontario, M3B 2S7, Canada

Location

Clinique Neuro Rive-Sud

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Hôpital Maisonneuve-Rosemont/Polyclinique;Recherche Clinique

Montreal, Quebec, H1T 2M4, Canada

Location

CHAUQ Hopital Enfant-Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

McGill Univeristy; Douglas Mental Health University Institute; Neurological and Psychiatric

Verdun, Quebec, H4H 1R3, Canada

Location

Hopital neurologique Pierre Wertheimer - CHU Lyon; Neurologie

Bron, 69677, France

Location

CHU de Limoges Hopital Dupuytren; Service de Medecine Geriatrique

Limoges, 87042, France

Location

Hopital Central; Neurologie

Nancy, 54035, France

Location

Hopital Nord Laennec

Nantes, 44093, France

Location

CHU de Rouen Hopital; Service de Neurologie

Rouen, 76031, France

Location

Hôpital Civil de Strasbourg

Strasbourg, 67091, France

Location

Univ Berlin; Klin fur Psychi & Psycho Charite

Berlin, 12203, Germany

Location

Bezirkskrankenhaus Günzburg

Günzburg, 89312, Germany

Location

Zentralinstitut fuer Seelische Gesundheit

Mannheim, 68159, Germany

Location

Ludwig-Maximilians-Univ.

München, 81377, Germany

Location

Klinikum rechts der Isar der Technischen Universität München

München, 81675, Germany

Location

Universitätsklinik Tübingen; Psychiatrie und Psychotherapie

Tübingen, 72076, Germany

Location

Fundació ACE

BArcelon, Barcelona, 08034, Spain

Location

Hospital General de Catalunya

San Cugat Del Valles, Barcelona, 08195, Spain

Location

Policlinica Guipuzcoa

Donostia / San Sebastian, Guipuzcoa, 20009, Spain

Location

Hospital de Cruces; Servicio de Neurologia

Barakaldo, Vizcaya, 48903, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, 2006, Spain

Location

Clinica Ruber, 4 planta; Servicio de Neurologia

Madrid, 28006, Spain

Location

The Rice Centre; Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

West London Research Unit; Brentford Lodge

Brentford, TW8 8DS, United Kingdom

Location

Royal Sussex County Hospital, CIRU Level 5

Brighton, BN2 5BE, United Kingdom

Location

Glasgow Memory Clinic

Glasgow, G20 0XA, United Kingdom

Location

The National Hospital for Neurology & Neurosurgery; Dementia Research Center

London, GT LON, WC1N 3BG, United Kingdom

Location

Southampton General Hospital; Pharmacy

Southampton, SO16 6YD, United Kingdom

Location

Moorgreen Hospital; Memory Assessment & Rsch Ctr

Southampton, SO30 3JB, United Kingdom

Location

Great Western Hosp.; Kingshill Research Ctr

Swindon, SN3 6BW, United Kingdom

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

crenezumab

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2012
• First Posted: November 8, 2012
• Study Start: December 7, 2012
• Primary Completion: February 8, 2017
• Study Completion: February 8, 2017
• Last Updated: February 20, 2020
• Results First Posted: February 12, 2020

Record last verified: 2020-02

Locations

US (47); GB (8); CA (13); DE (6); FR (6); ES (6)