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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: Placebo; Drug: 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).

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Fullerton, California, United States, 92835
      • Neurology Center of North Orange County
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Network
    • Simi Valley, California, United States, 93065
      • Southern California Research
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern Connecticut
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • Orlando, Florida, United States, 32806
      • Compass Research
    • Port Orange, Florida, United States, 32137
      • Progressive Medical Research
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research
    • The Villages, Florida, United States, 32162
      • Compass-The Villages
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Medical Research and Health Education Foundation
    • Decatur, Georgia, United States, 30033
      • NeuroStudies LLC
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
  • New York
    • Albany, New York, United States, 12208
      • Neurological Associates of Albany
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, Inc.
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer's Memory Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Lehigh Center for Clinical Research
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Neurological Associates, LTD
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Change from baseline in florbetapir-fluorine-18 positron emission tomography (PET) imaging in certain brain areas	Baseline and Week 24
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

Collaborators and Investigators

• Sponsor: Proclara Biosciences, Inc.
• Collaborators: Alzheimer's Association
• Investigators: Study Director: Proclara Biosciences, Proclara

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): February 6, 2019
• Study Completion (Actual): February 6, 2019

Study Registration Dates

• First Submitted: December 23, 2016
• First Submitted That Met QC Criteria: December 29, 2016
• First Posted (Estimate): January 2, 2017

Study Record Updates

• Last Update Posted (Actual): August 15, 2019
• Last Update Submitted That Met QC Criteria: August 14, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: amyloid; GAIM; anti-aBeta; anti-tau
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: NPT088-CL002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided