Multiple Dose Safety Study of NPT088 in Patients With Mild to Moderate Probable Alzheimer's Disease

Study Overview
=================
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).

Official Title
-----------------
A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation Study of NPT088 in Patients With Probable Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: NPT088
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants will receive monthly IV infusions of either low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months | Drug: NPT088<br>* IgG1 Fc-GAIM fusion protein, a recombinant fusion protein<br>* Other names: anti-Tau;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 2<br>Participants will receive monthly IV infusions of either mid-low dose NPT088 (6 participants) or placebo (3 participants) for a total of 6 months | Drug: NPT088<br>* IgG1 Fc-GAIM fusion protein, a recombinant fusion protein<br>* Other names: anti-Tau;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 3<br>Participants will receive monthly IV infusions of either mid-high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months | Drug: NPT088<br>* IgG1 Fc-GAIM fusion protein, a recombinant fusion protein<br>* Other names: anti-Tau;Drug: Placebo<br>* Placebo<br>|
| Experimental: Cohort 4<br>Participants will receive monthly IV infusions of either high dose NPT088 (16 participants) or placebo (8 participants) for a total of 6 months | Drug: NPT088<br>* IgG1 Fc-GAIM fusion protein, a recombinant fusion protein<br>* Other names: anti-Tau;Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with adverse events |  | Baseline to Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GAIM, amyloid, anti-aBeta, anti-tau