An Open-Label Crenezumab Study in Participants With Alzheimer's Disease

NCT03491150 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: BN400312017-002702-12
• Study Type: interventional
• Target: 149
• Locations: 16 countries
• Sites: 66

Brief Summary

In the BN40031 OLE study, a dose of crenezumab of 60 mg/kg intravenous (IV) every 4 weeks (Q4W) will be offered to all participants who complete Study BN29552 or BN29553 and who meet eligibility criteria in order to evaluate safety in participants on long-term crenezumab treatment and to investigate the effect of crenezumab on the underlying disease process and disease course as an exploratory efficacy objective.

Conditions

Alzheimer's Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An Adverse Event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to 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.

  Baseline up to 16 weeks after the last dose of study drug (up to 54 weeks).

• Percentage of Participants With Anti-Crenezumab Antibodies

  Participants were considered positive or negative for ADA based on their baseline and post-baseline sample results. The number and percentage of participants with confirmed positive ADA levels were determined for Crenezumab and Placebo groups. The prevalence of ADA at baseline was calculated as the proportion of participants with confirmed positive ADA levels at baseline relative to the total number of participants with a sample available at baseline. The incidence of treatment-emergent ADAs was determined as the proportion of participants with confirmed post-baseline positive ADAs relative to the total number of participants that had at least one post-baseline sample available for ADA analysis.

  Baseline up to end of study (up to 54 weeks).

Study Arms (2)

Parent Placebo

PLACEBO COMPARATOR

Participants (who were treated with Placebo in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).

Drug: Crenezumab

Parent Crenezumab

EXPERIMENTAL

Participants (who were treated with Crenezumab in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).

Drug: Crenezumab

Interventions

Crenezumab DRUG

Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.

Also known as: RO5490245

Parent Crenezumab; Parent Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Previous participation in Study BN29552 or BN29553 and completion of the Week 105 visit.
• Able to provide written informed consent by the patient or legally authorized representative, if required.
• Every effort to have the same caregiver participate throughout the duration of the OLE (Open Label Extension) study who also participated in Study BN29552 or BN29553.
• Willingness and ability to complete all aspects of the study \[including MRI (Magnetic Resonance Imaging), lumbar puncture \[if applicable\], and PET (Positron Emission Tomography) imaging \[if applicable\].
• Adequate visual and auditory acuity, in the investigator's judgment, sufficient to perform the neuropsychological testing.
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a protocol approved contraceptive method and agreement to refrain from donating eggs for at least 8 weeks after last dose.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a protocol approved contraceptive method for at least 8 weeks after last dose.

You may not qualify if:

• Patients who discontinued treatment permanently in Study BN29552 or BN29553 for safety reasons.
• Impaired coagulation.
• Evidence of more than 10 microbleeds and/or ARIA-H (amyloid-related imaging abnormalities-hemosiderin deposition) at the Study BN29552 or BN29553 Week 105 visit, as assessed by central review of MRI.
• Diagnosed with three recurrent, symptomatic ARIA-E (amyloid-related imaging abnormalities-edema/effusion) events or exacerbations of previous events.
• Presence of intracranial lesion that could potentially increase the risk of CNS (Central Nervous System) bleeding.
• At risk of suicide in the opinion of the investigator.
• Alcohol and/or substance abuse or dependence within the past 2 years and during the study.
• Inability to tolerate MRI procedures or contraindication to MRI, including, but not limited to, presence of pacemakers not compatible with MRI, aneurysm clips, artificial heart valves, ear implants, or foreign metal objects in the eyes, skin, or body that would contraindicate an MRI scan; or any other clinical history or examination finding that, in the judgment of the investigator, would pose a potential hazard in combination with MRI.
• Pregnant or lactating, or intending to become pregnant during the study.
• Any other severe or unstable medical condition that, in the opinion of the investigator or Sponsor, could be expected to progress, recur, or change to such an extent that it could put the patient at special risk, bias the assessment of the clinical or mental status of the patient to a significant degree, or interfere with the patient's ability to complete the study assessments.
• Chronic use of anticoagulants or participation in any other investigational drug treatment trial.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (66)

Shankle Clinic

Newport Beach, California, 92663, United States

Location

Anderson Clinical Research, Inc.

Redlands, California, 92374, United States

Location

University of California, Davis; Alzheimers Disease Center, Department of Neurology

Sacramento, California, 95817, United States

Location

UCSF - Memory and Aging Center

San Francisco, California, 94158, United States

Location

Neurological Research Inst

Santa Monica, California, 90404, United States

Location

Associated Neurologists PC - Danbury

Danbury, Connecticut, 06810, United States

Location

Institute for Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

Research Center for Clinical Studies, Inc.

Norwalk, Connecticut, 06851, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

Brain Matters Research, Inc.

Delray Beach, Florida, 33445, United States

Location

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 33414, United States

Location

Renstar Medical Research

Ocala, Florida, 34470, United States

Location

Bioclinica Research

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Stedman Clinical Trials, LLC

Tampa, Florida, 33613, United States

Location

NeuroStudies.net, LLC

Decatur, Georgia, 30033, United States

Location

Alexian Brothers Neurosci Inst

Elk Grove Village, Illinois, 60007, United States

Location

Southern Illinois University, School of Medicine

Springfield, Illinois, 62702, United States

Location

MidAmerica Neuroscience Institute

Prairie Village, Kansas, 66206, United States

Location

MMP Neurology

Scarborough, Maine, 04074, United States

Location

Precise Research Centers

Flowood, Mississippi, 39232, United States

Location

The Cognitive and Research Center of New Jersey

Springfield, New Jersey, 07081, United States

Location

Advanced Memory Research Institute of NJ

Toms River, New Jersey, 08755, United States

Location

Behavioral Health Research

Charlotte, North Carolina, 28211, United States

Location

Guilford Neurologic Associates

Greensboro, North Carolina, 27401, United States

Location

Oklahoma Clinical Research

Oklahoma City, Oklahoma, 73112, United States

Location

Summit Research Network Inc.

Portland, Oregon, 97210, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Senior Adults Specialty Research

Austin, Texas, 78757, United States

Location

Sentara Medical Group

Norfolk, Virginia, 23507, United States

Location

National Clinical Research Inc.-Richmond

Richmond, Virginia, 23294, United States

Location

Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre

Heidelberg West, Victoria, 3081, Australia

Location

Neurodegenerative Disorders Research; Neurology

West Perth, Western Australia, 6005, Australia

Location

Parkwood Hospital; Geriatric Medicine

London, Ontario, N6C 5J1, Canada

Location

Kawartha Centre - Redefining Healthy Aging

Peterborough, Ontario, K9H 2P4, Canada

Location

The Centre for Memory and Aging

Toronto, Ontario, M4G 3E8, Canada

Location

Devonshire Clinical Research Inc.

Woodstock, Ontario, N4S 5P5, Canada

Location

Terveystalo Tampere

Tampere, 33100, Finland

Location

Hopital La Grave; Place Lange

Toulouse Cedec, 31059, France

Location

Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie

München, 81675, Germany

Location

Prince of Wales Hospital; Dept. of Medicine & Therapeutics

Hong Kong, Hong Kong

Location

Fondazione Santa Lucia IRCCS

Rome, Lazio, 00179, Italy

Location

Ospedale San Giovanni Calibita Fatebenefratell;Neurologia

Rome, Lazio, 00186, Italy

Location

Vilnius University Hospital Santariskiu Clinic

Vilnius, 08661, Lithuania

Location

Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC

Culiacán, 80020, Mexico

Location

Hospital Uni; Dr. Jose E. Gonzalez

Monterrey, 64460, Mexico

Location

AVIX Investigación Clínica S.C

Monterrey, 64710, Mexico

Location

Hospital Universitario de Saltillo

Saltillo, 25000, Mexico

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

State Autonomous Healthcare Institution "Republican Clinical Neurological Center

Kazan', 420021, Russia

Location

State autonomous institution of healthcare Inter-regional clinical and diagnostic center

Kazan', 420101, Russia

Location

SHI City Psychoneurological Dispensary #7 (with Hospital)

Saint Petersburg, 190121, Russia

Location

Inha University Hospital

Incheon, 22332, South Korea

Location

Konkuk University Medical Center

Seoul, 05030, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Ewha Womans University Mokdong Hospital

Seoul, 07985, South Korea

Location

Fundació ACE

BArcelon, Barcelona, 08034, Spain

Location

Hospital General De Catalunya; Servicio de Neurologia

Sant Cugat del Vallès, Barcelona, 8195, Spain

Location

Hospital Mutua De Terrasa; Servicio de Neurologia

Terrassa, Barcelona, 08222, Spain

Location

Hospital Virgen del Puerto. Servicio de Neurología

Plasencia, Caceres, 10600, Spain

Location

Clinica Universitaria de Navarra; Servicio de Neurología

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, 28041, Spain

Location

Ondokuz Mayis Univ. Med. Fac.; Neurology

Samsun, 55139, Turkey (Türkiye)

Location

Surrey and Borders NHS Foundation Trust; Research and Development Departmant; Abraham Cowley Unit

Chertsey, KT16 0AE, United Kingdom

Location

Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

MeSH Terms

Conditions

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

Interventions

crenezumab

Limitations and Caveats

This study was discontinued due to an interim analysis in the BN29552 study, which indicated that Crenezumab was unlikely to meet its primary endpoint.

Results Point of Contact

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

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open Label Extension (OLE)

Study Record Dates

• First Submitted: March 15, 2018
• First Posted: April 9, 2018
• Study Start: April 11, 2018
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2019
• Last Updated: July 13, 2020
• Results First Posted: June 9, 2020

Record last verified: 2020-06

Locations

ME (4); DE (1); IT (2); US (32); HK (1); KR (4); ES (6); FI (1); RU (3); CA (4); GB (2); AU (2); LI (1); PL (1); FR (1); TU (1)