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

NCT ID: NCT03008161

Last Updated: 2019-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 83 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-31
• Study Completion Date: 2019-02-06

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).

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

NPT088

Intervention Type: DRUG

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Placebo

Intervention Type: DRUG

Placebo

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

Group Type: EXPERIMENTAL

NPT088

Intervention Type: DRUG

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Placebo

Intervention Type: DRUG

Placebo

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

Group Type: EXPERIMENTAL

NPT088

Intervention Type: DRUG

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Placebo

Intervention Type: DRUG

Placebo

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

Group Type: EXPERIMENTAL

NPT088

Intervention Type: DRUG

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Placebo

Intervention Type: DRUG

Placebo

Interventions

NPT088

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

IgG1; fusion protein; GAIM; anti-Abeta; anti-Tau

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alzheimer's Association

OTHER

Sponsor Role: collaborator

Proclara Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Proclara Biosciences

Role: STUDY_DIRECTOR

Proclara

Locations

ATP Clinical Research, Inc.

Costa Mesa, California, United States

Neurology Center of North Orange County

Fullerton, California, United States

Collaborative Neuroscience Network

Long Beach, California, United States

Southern California Research

Simi Valley, California, United States

Associated Neurologists of Southern Connecticut

Fairfield, Connecticut, United States

JEM Research Institute

Atlantis, Florida, United States

Indago Research and Health Center

Hialeah, Florida, United States

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 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

Axiom Clinical Research

Tampa, Florida, United States

Compass-The Villages

The Villages, Florida, United States

Medical Research and Health Education Foundation

Columbus, Georgia, United States

NeuroStudies LLC

Decatur, Georgia, United States

Princeton Medical Institute

Princeton, New Jersey, United States

Neurological Associates of Albany

Albany, New York, United States

Integrative Clinical Trials, Inc.

Brooklyn, New York, United States

Alzheimer's Memory Center

Charlotte, North Carolina, United States

Lehigh Center for Clinical Research

Allentown, Pennsylvania, United States

Abington Neurological Associates, Ltd

Willow Grove, Pennsylvania, United States

Neurology Clinic, PC

Cordova, Tennessee, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 24768993 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29067301 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28093972 (View on PubMed)

Other Identifiers

NPT088-CL002

Identifier Type: -

Identifier Source: org_study_id