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

Alzheimer Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03008161
• Other study ID #: NPT088-CL002
• Status: Completed
• Phase: Phase 1
• Start date: December 2016
• Est. completion date: February 6, 2019

Study information

• Verified date: August 2019
• Source: Proclara Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: February 6, 2019
• Est. primary completion date: February 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• NPT088
IgG1 Fc-GAIM fusion protein, a recombinant fusion protein
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Neurological Associates of Albany	Albany	New York
United States	Lehigh Center for Clinical Research	Allentown	Pennsylvania
United States	JEM Research Institute	Atlantis	Florida
United States	Integrative Clinical Trials, Inc.	Brooklyn	New York
United States	Alzheimer's Memory Center	Charlotte	North Carolina
United States	Medical Research and Health Education Foundation	Columbus	Georgia
United States	Neurology Clinic, PC	Cordova	Tennessee
United States	ATP Clinical Research, Inc.	Costa Mesa	California
United States	NeuroStudies LLC	Decatur	Georgia
United States	Associated Neurologists of Southern Connecticut	Fairfield	Connecticut
United States	Neurology Center of North Orange County	Fullerton	California
United States	Indago Research and Health Center	Hialeah	Florida
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Collaborative Neuroscience Network	Long Beach	California
United States	Miami Jewish Health Systems	Miami	Florida
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	Compass Research	Orlando	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	Princeton Medical Institute	Princeton	New Jersey
United States	Southern California Research	Simi Valley	California
United States	Axiom Clinical Research	Tampa	Florida
United States	Compass-The Villages	The Villages	Florida
United States	Abington Neurological Associates, Ltd	Willow Grove	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Proclara Biosciences, Inc.	Alzheimer's Association

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. Review. — View 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. — View 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-ß 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas		Baseline and Week 24
Other	Change from baseline in [18F] MNI-960 PET imaging in certain brain areas		Baseline and Week 24
Other	Change in CSF or blood biomarkers		Up to Week 32
Primary	Number of patients with adverse events		Baseline to Week 32
Secondary	Multiple dose pharmacokinetic (PK) serum concentrations of NPT088		Up to Week 32
Secondary	Multiple dose PK CSF concentrations of NPT088		Up to Week 32
Secondary	Multiple dose immunogenicity of NPT088		Up to Week 32