An Open-Label Crenezumab Study in Participants With Alzheimer's Disease (CREAD OLE)
Primary Purpose
Alzheimer's Disease
Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Crenezumab
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Dementia, Neurodegenerative Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurocognitive Disorders, Mental Disorders
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Sites / Locations
- Shankle Clinic
- Anderson Clinical Research, Inc.
- University of California, Davis; Alzheimers Disease Center, Department of Neurology
- UCSF - Memory and Aging Center
- Neurological Research Inst
- Associated Neurologists PC - Danbury
- Institute for Neurodegenerative Disorders
- Yale University School Of Medicine
- Research Center for Clinical Studies, Inc.
- Bradenton Research Center
- Brain Matters Research, Inc.
- Alzheimer's Research and Treatment Center
- Renstar Medical Research
- Bioclinica Research
- Progressive Medical Research
- Stedman Clinical Trials, LLC
- NeuroStudies.net, LLC
- Alexian Brothers Neurosci Inst
- Southern Illinois University, School of Medicine
- MidAmerica Neuroscience Institute
- MMP Neurology
- Precise Research Centers
- The Cognitive and Research Center of New Jersey
- Advanced Memory Research Institute of NJ
- Behavioral Health Research
- Guilford Neurologic Associates
- Oklahoma Clinical Research
- Summit Research Network Inc.
- Abington Neurological Associates
- Senior Adults Specialty Research
- Sentara Medical Group
- National Clinical Research Inc.-Richmond
- Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
- Neurodegenerative Disorders Research; Neurology
- Parkwood Hospital; Geriatric Medicine
- Kawartha Centre - Redefining Healthy Aging
- The Centre for Memory and Aging
- Devonshire Clinical Research Inc.
- Terveystalo Tampere
- Hopital La Grave; Place Lange
- Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
- Prince of Wales Hospital; Dept. of Medicine & Therapeutics
- Fondazione Santa Lucia IRCCS
- Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
- Inha University Hospital
- Konkuk University Medical Center
- Asan Medical Center
- Ewha Womans University Mokdong Hospital
- Vilnius University Hospital Santariskiu Clinic
- Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC
- Hospital Uni; Dr. Jose E. Gonzalez
- AVIX Investigación Clínica S.C
- Hospital Universitario de Saltillo
- Centrum Medyczne NeuroProtect
- State Autonomous Healthcare Institution "Republican Clinical Neurological Center
- State autonomous institution of healthcare Inter-regional clinical and diagnostic center
- SHI City Psychoneurological Dispensary #7 (with Hospital)
- Fundació ACE
- Hospital General De Catalunya; Servicio de Neurologia
- Hospital Mutua De Terrasa; Servicio de Neurologia
- Hospital Virgen del Puerto. Servicio de Neurología
- Clinica Universitaria de Navarra; Servicio de Neurología
- Hospital Universitario 12 de Octubre; Servicio de Neurologia
- Ondokuz Mayis Univ. Med. Fac.; Neurology
- Surrey and Borders NHS Foundation Trust; Research and Development Departmant; Abraham Cowley Unit
- Charing Cross Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Parent Placebo
Parent Crenezumab
Arm Description
Participants (who were treated with Placebo in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).
Participants (who were treated with Crenezumab in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03491150
Brief Title
An Open-Label Crenezumab Study in Participants With Alzheimer's Disease
Acronym
CREAD OLE
Official Title
A Multicenter, Open-Label, Long-Term Extension Of Phase III Studies (BN29552/BN29553) Of Crenezumab In Patients With Alzheimer's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
This study was discontinued due to an interim analysis in the BN29552 study, which indicated that Crenezumab was unlikely to meet its primary endpoint.
Study Start Date
April 11, 2018 (Actual)
Primary Completion Date
May 31, 2019 (Actual)
Study Completion Date
May 31, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Dementia, Neurodegenerative Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurocognitive Disorders, Mental Disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Model Description
Open Label Extension (OLE)
Masking
None (Open Label)
Allocation
N/A
Enrollment
149 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Parent Placebo
Arm Type
Placebo Comparator
Arm Description
Participants (who were treated with Placebo in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).
Arm Title
Parent Crenezumab
Arm Type
Experimental
Arm Description
Participants (who were treated with Crenezumab in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W).
Intervention Type
Drug
Intervention Name(s)
Crenezumab
Other Intervention Name(s)
RO5490245
Intervention Description
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
Primary Outcome Measure Information:
Title
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to 16 weeks after the last dose of study drug (up to 54 weeks).
Title
Percentage of Participants With Anti-Crenezumab Antibodies
Description
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.
Time Frame
Baseline up to end of study (up to 54 weeks).
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Shankle Clinic
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
Anderson Clinical Research, Inc.
City
Redlands
State/Province
California
ZIP/Postal Code
92374
Country
United States
Facility Name
University of California, Davis; Alzheimers Disease Center, Department of Neurology
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UCSF - Memory and Aging Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Neurological Research Inst
City
Santa Monica
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Associated Neurologists PC - Danbury
City
Danbury
State/Province
Connecticut
ZIP/Postal Code
06810
Country
United States
Facility Name
Institute for Neurodegenerative Disorders
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Yale University School Of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Research Center for Clinical Studies, Inc.
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06851
Country
United States
Facility Name
Bradenton Research Center
City
Bradenton
State/Province
Florida
ZIP/Postal Code
34205
Country
United States
Facility Name
Brain Matters Research, Inc.
City
Delray Beach
State/Province
Florida
ZIP/Postal Code
33445
Country
United States
Facility Name
Alzheimer's Research and Treatment Center
City
Lake Worth
State/Province
Florida
ZIP/Postal Code
33414
Country
United States
Facility Name
Renstar Medical Research
City
Ocala
State/Province
Florida
ZIP/Postal Code
34470
Country
United States
Facility Name
Bioclinica Research
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Progressive Medical Research
City
Port Orange
State/Province
Florida
ZIP/Postal Code
32127
Country
United States
Facility Name
Stedman Clinical Trials, LLC
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Facility Name
NeuroStudies.net, LLC
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
Facility Name
Alexian Brothers Neurosci Inst
City
Elk Grove Village
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Southern Illinois University, School of Medicine
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
MidAmerica Neuroscience Institute
City
Prairie Village
State/Province
Kansas
ZIP/Postal Code
66206
Country
United States
Facility Name
MMP Neurology
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
Precise Research Centers
City
Flowood
State/Province
Mississippi
ZIP/Postal Code
39232
Country
United States
Facility Name
The Cognitive and Research Center of New Jersey
City
Springfield
State/Province
New Jersey
ZIP/Postal Code
07081
Country
United States
Facility Name
Advanced Memory Research Institute of NJ
City
Toms River
State/Province
New Jersey
ZIP/Postal Code
08755
Country
United States
Facility Name
Behavioral Health Research
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28211
Country
United States
Facility Name
Guilford Neurologic Associates
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27401
Country
United States
Facility Name
Oklahoma Clinical Research
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73112
Country
United States
Facility Name
Summit Research Network Inc.
City
Portland
State/Province
Oregon
ZIP/Postal Code
97210
Country
United States
Facility Name
Abington Neurological Associates
City
Willow Grove
State/Province
Pennsylvania
ZIP/Postal Code
19090
Country
United States
Facility Name
Senior Adults Specialty Research
City
Austin
State/Province
Texas
ZIP/Postal Code
78757
Country
United States
Facility Name
Sentara Medical Group
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
National Clinical Research Inc.-Richmond
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23294
Country
United States
Facility Name
Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre
City
Heidelberg West
State/Province
Victoria
ZIP/Postal Code
3081
Country
Australia
Facility Name
Neurodegenerative Disorders Research; Neurology
City
West Perth
State/Province
Western Australia
ZIP/Postal Code
6005
Country
Australia
Facility Name
Parkwood Hospital; Geriatric Medicine
City
London
State/Province
Ontario
ZIP/Postal Code
N6C 5J1
Country
Canada
Facility Name
Kawartha Centre - Redefining Healthy Aging
City
Peterborough
State/Province
Ontario
ZIP/Postal Code
K9H 2P4
Country
Canada
Facility Name
The Centre for Memory and Aging
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4G 3E8
Country
Canada
Facility Name
Devonshire Clinical Research Inc.
City
Woodstock
State/Province
Ontario
ZIP/Postal Code
N4S 5P5
Country
Canada
Facility Name
Terveystalo Tampere
City
Tampere
ZIP/Postal Code
33100
Country
Finland
Facility Name
Hopital La Grave; Place Lange
City
Toulouse Cedec
ZIP/Postal Code
31059
Country
France
Facility Name
Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie
City
München
ZIP/Postal Code
81675
Country
Germany
Facility Name
Prince of Wales Hospital; Dept. of Medicine & Therapeutics
City
Hong Kong
Country
Hong Kong
Facility Name
Fondazione Santa Lucia IRCCS
City
Roma
State/Province
Lazio
ZIP/Postal Code
00179
Country
Italy
Facility Name
Ospedale San Giovanni Calibita Fatebenefratell;Neurologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00186
Country
Italy
Facility Name
Inha University Hospital
City
Incheon
ZIP/Postal Code
22332
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center
City
Seoul
ZIP/Postal Code
05030
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Ewha Womans University Mokdong Hospital
City
Seoul
ZIP/Postal Code
07985
Country
Korea, Republic of
Facility Name
Vilnius University Hospital Santariskiu Clinic
City
Vilnius
ZIP/Postal Code
08661
Country
Lithuania
Facility Name
Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC
City
Culiacan
ZIP/Postal Code
80020
Country
Mexico
Facility Name
Hospital Uni; Dr. Jose E. Gonzalez
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
AVIX Investigación Clínica S.C
City
Monterrey
ZIP/Postal Code
64710
Country
Mexico
Facility Name
Hospital Universitario de Saltillo
City
Saltillo
ZIP/Postal Code
25000
Country
Mexico
Facility Name
Centrum Medyczne NeuroProtect
City
Warszawa
ZIP/Postal Code
01-684
Country
Poland
Facility Name
State Autonomous Healthcare Institution "Republican Clinical Neurological Center
City
Kazan
ZIP/Postal Code
420021
Country
Russian Federation
Facility Name
State autonomous institution of healthcare Inter-regional clinical and diagnostic center
City
Kazan
ZIP/Postal Code
420101
Country
Russian Federation
Facility Name
SHI City Psychoneurological Dispensary #7 (with Hospital)
City
St. Petersburg
ZIP/Postal Code
190121
Country
Russian Federation
Facility Name
Fundació ACE
City
BArcelon
State/Province
Barcelona
ZIP/Postal Code
08034
Country
Spain
Facility Name
Hospital General De Catalunya; Servicio de Neurologia
City
Sant Cugat del Valles
State/Province
Barcelona
ZIP/Postal Code
8195
Country
Spain
Facility Name
Hospital Mutua De Terrasa; Servicio de Neurologia
City
Terrassa
State/Province
Barcelona
ZIP/Postal Code
08222
Country
Spain
Facility Name
Hospital Virgen del Puerto. Servicio de Neurología
City
Plasencia
State/Province
Caceres
ZIP/Postal Code
10600
Country
Spain
Facility Name
Clinica Universitaria de Navarra; Servicio de Neurología
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Hospital Universitario 12 de Octubre; Servicio de Neurologia
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
Ondokuz Mayis Univ. Med. Fac.; Neurology
City
Samsun
ZIP/Postal Code
55139
Country
Turkey
Facility Name
Surrey and Borders NHS Foundation Trust; Research and Development Departmant; Abraham Cowley Unit
City
Chertsey
ZIP/Postal Code
KT16 0AE
Country
United Kingdom
Facility Name
Charing Cross Hospital
City
London
ZIP/Postal Code
W6 8RF
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
An Open-Label Crenezumab Study in Participants With Alzheimer's Disease
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