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

Alzheimer's Disease Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03491150
• Other study ID #: BN40031
• Secondary ID: 2017-002702-12
• Status: Terminated
• Phase: Phase 3
• Start date: April 11, 2018
• Est. completion date: May 31, 2019

Study information

• Verified date: June 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 149
• Est. completion date: May 31, 2019
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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

Locations

Country	Name	City	State
Australia	Heidelberg Repatriation Hospital; Medical and Cognitive Research Centre	Heidelberg West	Victoria
Australia	Neurodegenerative Disorders Research; Neurology	West Perth	Western Australia
Canada	Parkwood Hospital; Geriatric Medicine	London	Ontario
Canada	Kawartha Centre - Redefining Healthy Aging	Peterborough	Ontario
Canada	The Centre for Memory and Aging	Toronto	Ontario
Canada	Devonshire Clinical Research Inc.	Woodstock	Ontario
Finland	Terveystalo Tampere	Tampere
France	Hopital La Grave; Place Lange	Toulouse Cedec
Germany	Klinikum rechts der Isar der TU München; Klinik für Psychiatrie und Psychotherapie	München
Hong Kong	Prince of Wales Hospital; Dept. of Medicine & Therapeutics	Hong Kong
Italy	Fondazione Santa Lucia IRCCS	Roma	Lazio
Italy	Ospedale San Giovanni Calibita Fatebenefratell;Neurologia	Roma	Lazio
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Lithuania	Vilnius University Hospital Santariskiu Clinic	Vilnius
Mexico	Hospital Angeles de Culiacán, Neurociencias Estudios Clínicos SC	Culiacan
Mexico	AVIX Investigación Clínica S.C	Monterrey
Mexico	Hospital Uni; Dr. Jose E. Gonzalez	Monterrey
Mexico	Hospital Universitario de Saltillo	Saltillo
Poland	Centrum Medyczne NeuroProtect	Warszawa
Russian Federation	State Autonomous Healthcare Institution "Republican Clinical Neurological Center	Kazan
Russian Federation	State autonomous institution of healthcare Inter-regional clinical and diagnostic center	Kazan
Russian Federation	SHI City Psychoneurological Dispensary #7 (with Hospital)	St. Petersburg
Spain	Fundació ACE	BArcelon	Barcelona
Spain	Hospital Universitario 12 de Octubre; Servicio de Neurologia	Madrid
Spain	Clinica Universitaria de Navarra; Servicio de Neurología	Pamplona	Navarra
Spain	Hospital Virgen del Puerto. Servicio de Neurología	Plasencia	Caceres
Spain	Hospital General De Catalunya; Servicio de Neurologia	Sant Cugat del Valles	Barcelona
Spain	Hospital Mutua De Terrasa; Servicio de Neurologia	Terrassa	Barcelona
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
United Kingdom	Surrey and Borders NHS Foundation Trust; Research and Development Departmant; Abraham Cowley Unit	Chertsey
United Kingdom	Charing Cross Hospital	London
United States	Senior Adults Specialty Research	Austin	Texas
United States	Bradenton Research Center	Bradenton	Florida
United States	Behavioral Health Research	Charlotte	North Carolina
United States	Associated Neurologists PC - Danbury	Danbury	Connecticut
United States	NeuroStudies.net, LLC	Decatur	Georgia
United States	Brain Matters Research, Inc.	Delray Beach	Florida
United States	Alexian Brothers Neurosci Inst	Elk Grove Village	Illinois
United States	Precise Research Centers	Flowood	Mississippi
United States	Guilford Neurologic Associates	Greensboro	North Carolina
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Shankle Clinic	Newport Beach	California
United States	Sentara Medical Group	Norfolk	Virginia
United States	Research Center for Clinical Studies, Inc.	Norwalk	Connecticut
United States	Renstar Medical Research	Ocala	Florida
United States	Oklahoma Clinical Research	Oklahoma City	Oklahoma
United States	Bioclinica Research	Orlando	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Summit Research Network Inc.	Portland	Oregon
United States	MidAmerica Neuroscience Institute	Prairie Village	Kansas
United States	Anderson Clinical Research, Inc.	Redlands	California
United States	National Clinical Research Inc.-Richmond	Richmond	Virginia
United States	University of California, Davis; Alzheimers Disease Center, Department of Neurology	Sacramento	California
United States	UCSF - Memory and Aging Center	San Francisco	California
United States	Neurological Research Inst	Santa Monica	California
United States	MMP Neurology	Scarborough	Maine
United States	Southern Illinois University, School of Medicine	Springfield	Illinois
United States	The Cognitive and Research Center of New Jersey	Springfield	New Jersey
United States	Stedman Clinical Trials, LLC	Tampa	Florida
United States	Advanced Memory Research Institute of NJ	Toms River	New Jersey
United States	Abington Neurological Associates	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Lithuania,  Mexico,  Poland,  Russian Federation,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).
Primary	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).