Clinical trial NCT03008161: Multiple Dose Safety Study of NPT088 in Patients With Mild to Moderate Probable Alzheimer's Disease
Official title: A Phase 1 Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose Escalation Study of NPT088 in Patients With Probable Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: GAIM
amyloid
anti-aBeta
anti-tau
Lead sponsor: Proclara Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alzheimer's Association
First posted: 2017-01-02
Enrollment: 83
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: Baseline to Week 32
Secondary outcomes:
measure: Multiple dose pharmacokinetic (PK) serum concentrations of NPT088
timeFrame: Up to Week 32
measure: Multiple dose PK CSF concentrations of NPT088
timeFrame: Up to Week 32
measure: Multiple dose immunogenicity of NPT088
timeFrame: Up to Week 32
Other outcomes:
measure: Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas
timeFrame: Baseline and Week 24
measure: Change from baseline in [18F] MNI-960 PET imaging in certain brain areas
timeFrame: Baseline and Week 24
measure: Change in CSF or blood biomarkers
timeFrame: Up to Week 32
Locations:
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Fullerton
country: United States
facility: Neurology Center of North Orange County
state: California
city: Long Beach
country: United States
facility: Collaborative Neuroscience Network
state: California
city: Simi Valley
country: United States
facility: Southern California Research
state: California
city: Fairfield
country: United States
facility: Associated Neurologists of Southern Connecticut
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Miami
country: United States
facility: Miami Jewish Health Systems
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research
state: Florida
city: The Villages
country: United States
facility: Compass-The Villages
state: Florida
city: Columbus
country: United States
facility: Medical Research and Health Education Foundation
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies LLC
state: Georgia
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials, Inc.
state: New York
city: Charlotte
country: United States
facility: Alzheimer's Memory Center
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Center for Clinical Research
state: Pennsylvania
city: Willow Grove
country: United States
facility: Abington Neurological Associates, Ltd
state: Pennsylvania
city: Cordova
country: United States
facility: Neurology Clinic, PC
state: Tennessee
Study officials:
affiliation: Proclara
name: Proclara Biosciences
role: STUDY_DIRECTOR
References:
citation: Krishnan R, Tsubery H, Proschitsky MY, Asp E, Lulu M, Gilead S, Gartner M, Waltho JP, Davis PJ, Hounslow AM, Kirschner DA, Inouye H, Myszka DG, Wright J, Solomon B, Fisher RA. A bacteriophage capsid protein provides a general amyloid interaction motif (GAIM) that binds and remodels misfolded protein assemblies. J Mol Biol. 2014 Jun 26;426(13):2500-19. doi: 10.1016/j.jmb.2014.04.015. Epub 2014 Apr 22.
citation: Levenson JM, Schroeter S, Carroll JC, Cullen V, Asp E, Proschitsky M, Chung CH, Gilead S, Nadeem M, Dodiya HB, Shoaga S, Mufson EJ, Tsubery H, Krishnan R, Wright J, Solomon B, Fisher R, Gannon KS. NPT088 reduces both amyloid-beta and tau pathologies in transgenic mice. Alzheimers Dement (N Y). 2016 Jul 14;2(3):141-155. doi: 10.1016/j.trci.2016.06.004. eCollection 2016 Sep.
citation: Krishnan R, Hefti F, Tsubery H, Lulu M, Proschitsky M, Fisher R. Conformation as the Therapeutic Target for Neurodegenerative Diseases. Curr Alzheimer Res. 2017;14(4):393-402. doi: 10.2174/1567205014666170116152622.