Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease, ABBV-1758
Brief summary
Alzheimer's disease (AD) is a progressive, irreversible neurological disorder and is the most common cause of dementia in the elderly population. Clinical symptoms of the disease may begin with occasional forgetfulness such as misplacement of items, forgetting important dates or events, and may progress to noticeable memory loss, increased confusion and agitation, and eventually, loss of independence and non-responsiveness. The purpose of this study is to test how safe ABBV-1758 is, how well it works, how the body processes it and what effects it has on the body. ABBV-1758 is an investigational drug being developed for the treatment of Alzheimer's disease. This study is conducted in 3 stages. Stage A is a multiple ascending dose study with a 1 in 5 chance (4:1 randomization) that participants are assigned to receive placebo. Stage B is a dose expansion phase, also using 4:1 randomization for ABBV-1758 or placebo. Stage C enrolls Japanese and Chinese participants with the same randomization scheme. Approximately 210 participants will be enrolled at about 55 sites in the United States, China, and Japan. Participants will receive intravenous (IV) or subcutaneous (SC) doses of ABBV-1758 or placebo once every 4 weeks (Q4W) for 24 weeks and will be followed for additional 12 weeks in the Follow-up Period. Participants will have the option of participating in a 12-month, blinded Extension Period receiving ABBV-1758 or placebo based on amyloid PET results. There may be higher treatment burden for participants in this trial compared to their standard of care due to study procedures. Participants will attend regular visits during the study at a hospital or clinic. The safety of the treatment will be checked by medical assessments, blood tests, and completing questionnaires.
Interventions
DRUGABBV-1758
Intravenous (IV) or Subcutaneous (SC)
DRUGPlacebo for ABBV-1758
Intravenous (IV) or Subcutaneous (SC)
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Participants meeting all the following criteria for Alzheimer's disease (AD): * In regions where timely testing is feasible (e.g., results available within 4 weeks of Visit 1), plasma biomarker that is predictive of elevated brain amyloid at Screening for participants that do not have known elevated brain amyloid based on previous amyloid positron emission tomography (PET) results. * Participants with amyloid positron emission tomography PET scan results consistent with significant amyloid pathology (as determined by a Centiloid value of 50 or higher). * Participants must have a Mini-Mental State Examination (MMSE) score of 20 or higher at Screening.
Exclusion criteria
* Participants with screening magnetic resonance imaging (MRI) that show evidence of another potential etiology for progressive dementia. * Participants who have any current serious conditions or illnesses that are not adequately controlled, or any conditions that, in the investigator's opinion, could interfere with the analyses in this study, including but not limited to psychiatric, neurologic (other than AD), cardiovascular, hepatic, renal, gastroenterological, respiratory, endocrinologic, immunologic, or hematologic, metabolic, pulmonary, ophthalmologic, dermatologic, and/or any history of abnormal laboratory results that are indicative of significant disease(s). * Participants who had prior exposure to ABBV-1758 or any history of exposure to anti-amyloid beta monoclonal antibody (mAb) treatment. * Participants with other significant pathological findings on brain MRI at screening, including but not limited to: * Evidence of vasogenic edema * 4 or more microhemorrhages (defined as 10 mm or less at the greatest diameter) * Any macrohemorrhage (defined as greater than 10 mm at the greatest diameter) * Any superficial siderosis * Severe white matter disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Experiencing Adverse Events (AEs) | Up to approximately 40 weeks | An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with the treatment. The investigator assesses the relationship of each event to the use of study drug. |
| Percentage of Participants with Abnormal Change from Baseline in Clinical Laboratory Test Results | Up to approximately 40 weeks | Number of participants with abnormal change in clinical laboratory test results like hematology will be assessed. |
| Percentage of Participants With Amyloid-Related Imaging Abnormalities (ARIA) | Up to approximately 40 weeks | Amyloid related imaging abnormalities represent a spectrum of magnetic resonance imaging findings primarily observed in participants undergoing treatment with anti-amyloid therapies. |
| Percentage of Participants with Abnormal Change From Baseline in Vital Sign Measurements | Up to approximately 40 weeks | Number of participants with abnormal change from baseline in vital sign measurements like systolic and diastolic blood pressure will be assessed. |
| Percentage of Participants with Abnormal Change From Baseline in Electrocardiograms (ECGs) Parameters | Up to approximately 40 weeks | 12-lead resting ECGs will be recorded. Parameters include heart rate, PR interval, QT interval, QRS duration, and QT interval corrected using Fridericia's formula (QTcF). |
| Percentage of Participants Experiencing Any Suicidal Ideation or Suicidal Behavior As Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) | Up to approximately 40 weeks | The C-SSRS is a clinician-rated instrument that reports the severity of both suicidal ideation and behavior, with a higher score denoting more severe suicidal ideation and behavior. |
| Stage A, B, and C: Change from Baseline in Brain Amyloid Load | Up to approximately 28 Weeks | Measured by amyloid positron emission tomography (PET) |
| Stage A and C: Maximum Plasma Concentration (Cmax) of ABBV-1758 | Up to approximately 40 weeks | Cmax of ABBV-1758 |
| Stage A and C: Time to Cmax (Tmax) of ABBV-1758 | Up to approximately 40 weeks | Tmax of ABBV-1758 |
| Stage A and C: Trough Concentration measured at the end of a dosing interval at steady state (Ctrough) of ABBV-1758 | Up to approximately 40 weeks | Ctrough of ABBV-1758 |
| Stage A and C: Area under the Plasma Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of ABBV-1758 | Up to approximately 40 weeks | AUCtau of ABBV-1758 |
| Stage A and C: Average Serum Concentration at Steady-State (Cav,ss) of ABBV-1758 | Up to approximately 40 weeks | Cav,ss of ABBV-1758 |
| Stage A and C: Accumulation ratio for (AUCtau) of ABBV-1758 | Up to approximately 40 weeks | AUCtau of ABBV-1758 |
| Stage A and C: Total Body Clearance (CL) of ABBV-1758 | Up to approximately 40 weeks | CL of ABBV-1758 |
| Stage A and C: Apparent Clearance (CL/F) of ABBV-1758 | Up to approximately 40 weeks | CL/F of ABBV-1758 |
| Stage A and C: Volume of Distribution at Steady-State (Vss) | Up to approximately 40 weeks | Vss of ABBV-1758 |
| Stage A and C: Apparent Volume of Distribution during the Terminal Phase (Vz) | Up to approximately 40 weeks | Vz of ABBV-1758 |
| Stage A and C: Terminal Phase Elimination Rate Constant (β) of ABBV-1758 | Up to approximately 40 weeks | β of ABBV-1758 |
| Stage A and C: Terminal Phase Elimination Half-Life (t1/2) of ABBV-1758 | Up to approximately 40 weeks | Terminal phase elimination half-life of ABBV-1758 |
| Stage A and C: Effective Half-Life (T1/2,eff) | Up to approximately 40 weeks | T1/2,eff of ABBV-1758 |
Countries
China, United States
Contacts
CONTACTABBVIE CALL CENTER
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed