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

NCT03008161 | Completed Phase 1 DMC

• 1 other identifier: NPT088-CL002
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 23

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.

Conditions

Alzheimer Disease

Keywords

GAIM; amyloid; anti-aBeta; anti-tau

Outcome Measures

Primary Outcomes (1)

• Number of patients with adverse events

  Baseline to Week 32

Secondary Outcomes (3)

• 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 Outcomes (3)

• 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

Study Arms (4)

Cohort 1

EXPERIMENTAL

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; Drug: Placebo

Cohort 2

EXPERIMENTAL

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; Drug: Placebo

Cohort 3

EXPERIMENTAL

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; Drug: Placebo

Cohort 4

EXPERIMENTAL

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; Drug: Placebo

Interventions

NPT088 DRUG

IgG1 Fc-GAIM fusion protein, a recombinant fusion protein

Also known as: IgG1, fusion protein, GAIM, anti-Abeta, anti-Tau

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo DRUG

Placebo

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• Proclara Biosciences, Inc.: lead
• Alzheimer's Association: collaborator

Study Sites (23)

ATP Clinical Research, Inc.

Costa Mesa, California, 92626, United States

Location

Neurology Center of North Orange County

Fullerton, California, 92835, United States

Location

Collaborative Neuroscience Network

Long Beach, California, 90806, United States

Location

Southern California Research

Simi Valley, California, 93065, United States

Location

Associated Neurologists of Southern Connecticut

Fairfield, Connecticut, 06824, United States

Location

JEM Research Institute

Atlantis, Florida, 33462, United States

Location

Indago Research and Health Center

Hialeah, Florida, 33012, United States

Location

Alzheimer's Research and Treatment Center

Lake Worth, Florida, 33449, United States

Location

Miami Jewish Health Systems

Miami, Florida, 33137, United States

Location

Medical Research Group of Central Florida

Orange City, Florida, 32763, United States

Location

Compass Research

Orlando, Florida, 32806, United States

Location

Progressive Medical Research

Port Orange, Florida, 32137, United States

Location

Axiom Clinical Research

Tampa, Florida, 33609, United States

Location

Compass-The Villages

The Villages, Florida, 32162, United States

Location

Medical Research and Health Education Foundation

Columbus, Georgia, 31909, United States

Location

NeuroStudies LLC

Decatur, Georgia, 30033, United States

Location

Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Neurological Associates of Albany

Albany, New York, 12208, United States

Location

Integrative Clinical Trials, Inc.

Brooklyn, New York, 11229, United States

Location

Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Lehigh Center for Clinical Research

Allentown, Pennsylvania, 18104, United States

Location

Abington Neurological Associates, Ltd

Willow Grove, Pennsylvania, 19090, United States

Location

Neurology Clinic, PC

Cordova, Tennessee, 38018, United States

Location

Related Publications (3)

• 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.

  PMID: 24768993 BACKGROUND

• 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.

  PMID: 29067301 BACKGROUND

• 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.

  PMID: 28093972 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Immunoglobulin G

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Proclara Biosciences

  Proclara

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2016
• First Posted: January 2, 2017
• Study Start: December 1, 2016
• Primary Completion: February 6, 2019
• Study Completion: February 6, 2019
• Last Updated: August 15, 2019

Record last verified: 2019-08

Locations

US (23)