Alzheimer's Disease
Conditions
Keywords
Dementia, Neurodegenerative Diseases, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurocognitive Disorders, Mental Disorders
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.
Interventions
DRUGCrenezumab
Crenezumab was administered by intravenous (IV) infusion at 60mg/kg as per the dosing schedule described above.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open Label Extension (OLE)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 16 weeks after the last dose of study drug (up to 54 weeks). | 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 | Baseline up to end of study (up to 54 weeks). | 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. |
Countries
Australia, Canada, Finland, France, Germany, Hong Kong, Italy, Lithuania, Mexico, Poland, Russia, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 66 centers in 16 countries.
Pre-assignment details
A total of 149 participants were enrolled at 66 centers. These 149 participants represented the Safety Analysis population and data for this population is presented here.
Participants by arm
| Arm | Count |
|---|---|
| Parent Placebo Participants (who were treated with Placebo in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W). | 76 |
| Parent Crenezumab Participants (who were treated with Crenezumab in the BN29552/BN29553 Studies) received intravenous (IV) infusion of Crenezumab every 4 weeks (Q4W). | 73 |
| Total | 149 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Study Terminated by Sponsor | 74 | 70 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Parent Placebo | Parent Crenezumab | Total |
|---|---|---|---|
| Age, Continuous | 73.8 Years STANDARD_DEVIATION 7.6 | 72.0 Years STANDARD_DEVIATION 7.6 | 72.9 Years STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized Asian | 4 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 69 Participants | 69 Participants | 138 Participants |
| Race/Ethnicity, Customized Not Stated | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 72 Participants | 67 Participants | 139 Participants |
| Sex: Female, Male Female | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Male | 39 Participants | 35 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 73 |
| other Total, other adverse events | 4 / 76 | 4 / 73 |
| serious Total, serious adverse events | 3 / 76 | 4 / 73 |
Outcome results
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.
Time frame: Baseline up to 16 weeks after the last dose of study drug (up to 54 weeks).
Population: The Safety analysis population was defined as all participants who consented to the OLE study, including those who enrolled in the OLE but did not receive open-label treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Parent Placebo | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 32.9 Percentage of Participants |
| Parent Placebo | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 3.9 Percentage of Participants |
| Parent Crenezumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 42.5 Percentage of Participants |
| Parent Crenezumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 5.5 Percentage of Participants |
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.
Time frame: Baseline up to end of study (up to 54 weeks).
Population: Please note that for this Outcome Measure, no Participants were evaluated at all as the existing immunogenicity data from a parent study (Study BN29552) showed a low potential of Crenezumab to induce Anti-Drug Antibodies (ADAs).