Alzheimer Disease
Conditions
Keywords
GAIM, amyloid, anti-aBeta, anti-tau
Brief summary
The purpose of the study is to evaluate the safety and tolerability of multiple doses of NPT088 in patients with mild to moderate probable Alzheimer's Disease. The study will also evaluate the pharmacokinetics, immunogenicity and exploratory pharmacodynamic characteristics of multiple doses of NPT088.
Detailed description
This study is a multicenter Phase 1, randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation safety and tolerability study of NPT088 or placebo in patients with Probable AD with a MMSE score of 16-27. Enrolled patients will receive an intravenous infusion of NPT088 or placebo once a month for six months during this study. Four dose cohorts are planned with the first two cohorts enrolling 9 patients each (6 NPT088: 3 placebo) and the final two cohorts enrolling 24 patients each (16 NPT088: 8 placebo) for a total of 66 patients (44 NPT088: 22 placebo).
Interventions
DRUGNPT088
IgG1 Fc-GAIM fusion protein, a recombinant fusion protein
DRUGPlacebo
Placebo
Sponsors
Alzheimer's Association
Proclara Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
For enrollment in the study, participants must * be between 50 and 85 years of age, inclusive * have a Mini Mental State Examination (MMSE) scores between 16-27 (inclusive) * have a Modified Hachinski Score of less than or equal to 4 * have a diagnosis of Probable Alzheimer's Disease (AD) according to consensus criteria defined by the National Institute on Aging-Alzheimer's Association work group * have a Clinical Dementia Rating Scale (CDR) of 0.5 or 1.0, with the memory box score equal to or greater than 0.5 * have a positive florbetapir positron emission tomography (PET) amyloid scan * consent to apolipoprotein E (ApoE) genotyping * be willing to undergo repeat Magnetic Resonance Imaging (MRI) and PET imaging * be on stable doses of allowed medications for at least 30 days prior to Screening. Concurrent treatment with cholinesterase inhibitors and/or memantine is allowed * be in good healthy apart from the clinical diagnosis of AD * have a dedicated Caregiver who provides care at least 4 hours a day for 4 days a week and will provide informed consent for their participation
Exclusion criteria
For enrollment in the study, participants must NOT: * have a history of, or screening MRI indicative of any significant brain abnormality * have any major medical illness or unstable medical condition or in the opinion of the Investigator have any reason that may interfere with the participants ability to comply with the study procedures and abide by study restrictions or with the ability to interpret safety data * reside in a nursing home or need 24-hour care and supervision * take excluded medications * have exclusionary values on the Screening blood and urine sample * have been treated with immunomodulators to treat AD * have participated in an investigational drug or device study within 90 days * have a known allergy to study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of patients with adverse events | Baseline to Week 32 |
Secondary
| Measure | Time frame |
|---|---|
| Multiple dose pharmacokinetic (PK) serum concentrations of NPT088 | Up to Week 32 |
| Multiple dose PK CSF concentrations of NPT088 | Up to Week 32 |
| Multiple dose immunogenicity of NPT088 | Up to Week 32 |
Other
| Measure | Time frame |
|---|---|
| Change from baseline in [18F] MNI-960 PET imaging in certain brain areas | Baseline and Week 24 |
| Change in CSF or blood biomarkers | Up to Week 32 |
| Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas | Baseline and Week 24 |
Countries
United States
Outcome results
None listed