Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease, AD, Dementia, Monoclonal Antibody
Brief summary
This is a multicentre, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early AD followed by an Extension. The double-blind part is 72 weeks long, followed by an extension.
Detailed description
The purpose of this study is to find out whether treatment with VHB937 is safe and beneficial in people with early Alzheimer's disease. The study will evaluate the safety of VHB937, as well as its effects on memory and other thinking abilities, on daily activities, and on changes in the brain. The study will also observe and measure how VHB937 is processed by the body and how the body responds to it.
Interventions
BIOLOGICALVHB937
VHB937 solution for infusion
OTHERPlacebo
Solution for infusion
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Blinded placebo for infusion
Intervention model description
Double-blind, Randomized
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Male or female participants 50 to 85 years of age * Diagnosis of Mild Cognitive Impairment (MCI) due to AD or mild AD * Clinical Dementia Rating (CDR) Global score of 0.5 or 1.0 * Confirmation of AD based on cerebral spinal fluid (CSF) biomarkers or amyloid PET imaging * Reliable study partner who can accompany the participant at study visits * If on symptomatic AD treatment (AChEIs/memantine), on a stable dose prior to starting study treatment Key
Exclusion criteria
* Dementia due to a condition other than AD, including but not limited to, frontal temporal dementia, Parkinson's disease, dementia with Lewy bodies, Huntington disease, vascular dementia. * History or current diagnosis of cardiac conditions or ECG abnormalities indicating significant risk of safety for participants in the study * Transient ischemic attacks (TIA) or stroke occurring within 12 months * Clinical evidence of liver or renal disease/injury * Current major depressive episode that is not adequately controlled, history of schizophrenia, other chronic psychosis * Significant neurological disease other than dementia (e.g. serious brain infection, traumatic brain injury, multiple concussions, epilepsy or recurrent seizures * Presence of suicidal ideation within 6 months or suicidal behavior within 2 years before Screening * Presence of cancer, HIV, Hep B, Hep C, uncontrolled thyroid disease, uncontrolled diabetes * Taking any prohibited medications Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in the Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) | Baseline and Week 72 | The CDR is a measure of cognition and function, widely used in clinical research in AD. The scale assesses six domains: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. Based on in-depth semi-structured interview, each domain is assigned a score, which is summed to obtain the Sum of Boxes (SB) score, ranging from 0 to 18 with higher scores indicating worse condition |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) | From First treatment to end of study (up to 63 months approximately) | Incidence and severity of AEs and SAEs by treatment group, including Safety findings, Laboratory tests, Vital signs and, ECG findings qualifying and reported as AEs. |
| Change from Baseline in Clinical Dementia Rating scale - Sum of Boxes (CDR-SB) | Baseline over time until Week 72 | The CDR is a measure of cognition and function, widely used in clinical research in AD. The scale assesses six domains: Memory, Orientation, Judgment \& Problem Solving, Community Affairs, Home \& Hobbies, and Personal Care. |
| Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog14) | Baseline over time until Week 72 | The ADAS-Cog is is a 14-item clinical assessment tool to measure cognition. The ADAS-Cog14 score ranges between 0 and 90, with higher scores indicating worse cognitive performance |
| Change from Baseline in instrumental activities of daily living (iADL) on the Alzheimers Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale | Baseline over time until Week 72 | The ADCS-ADL is a 23-item study partner scale designed to assess the ability of patients with AD to carry out basic activities of daily living (bADLs) and instrumental activities of daily living (iADLs). For each item, the study partner is asked whether the participant attempted the activity in the 4 preceding weeks. Where 'yes' is the answer, the study partner is asked to rate the patient's level of performance according to a set of descriptors tailored to that activity. Scores on iADL sub-scale range between 0 and 59, with lower scores reflecting greater disease severity |
| Pharmacokinetic parameters of VHB937 in serum - Cmax | Baseline over time until Week 72 | Cmax - The maximum concentration of VHB937 in serum |
| Pharmacokinetic parameters of VHB937 in serum - Tmax | Baseline over time until Week 72 | Tmax - The time to reach the maximum concentration of VHB937 in serum |
| Pharmacokinetic parameters of VHB937 in serum - Ctrough | Baseline over time until Week 72 | Ctrough - Minimum observed concentration of VHB937 in CSF |
| VHB937 immunogenicity in serum | Baseline over time until Week 72 | Determination of anti-VHB937 antibodies in serum at selected timepoints |
Countries
Australia, Canada, China, Czechia, France, Germany, Italy, Japan, Netherlands, Poland, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTNovartis Pharmaceuticals
Outcome results
None listed