Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease

NCT ID: NCT02547818

Last Updated: 2021-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

620 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-09-15

Study Completion Date

2020-11-18

Brief Summary

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This is a global Phase III, randomized, double-blinded, placebo-controlled study for subjects with evidence of early AD. The protocol is designed to determine whether ALZT-OP1 combination treatment (ALZT-OP1a + ALZT-OP1b) will slow down, arrests, or reverse cognitive and functional decline, in subjects with evidence of early stage Alzheimer's disease (AD).

Detailed Description

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This Phase III study is designed as a randomized, double-blinded, placebo-controlled study for subjects with evidence of early AD. The study will evaluate safety and tolerability, efficacy as measured by CDR-SB, and will determine if the combination therapy ALZT-OP1 will slow down, arrests, or reverse cognitive and functional decline in an early stage AD population.

Subjects will be randomly assigned to one of four treatment arms: Group I will consist of ALZT-OP1a (cromolyn) for inhalation, plus an oral placebo tablet; OR the Group II arm, which will consist of ALZT-OP1 combination therapy ALZT-OP1a (cromolyn) for inhalation, plus ALZT-OP1b (ibuprofen) tablet for oral administration; OR to the Group III arm, which will consist of inhaled placebo, plus ALZT-OP1b (ibuprofen) tablet for oral administration; OR to the Group IV placebo arm, which will consist of inhaled placebo plus an oral placebo tablet.

A minimum of 400 evaluable subjects will be randomized to receive one of four possible treatment assignments containing various combinations of active study drug or placebo.

To account for subject dropouts (estimated rate of 30%), it is anticipated that up to 600 (or 150 subjects per treatment arm) may be recruited and randomized, to achieve a minimum of 100 evaluable subjects per treatment arm.

Conditions

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Alzheimer's Disease

Keywords

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Early stage AD MCI aMCI prodromal Memory loss Memory problems Aging Early Alzheimer's Disease Early AD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Group I

ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.

Group Type ACTIVE_COMPARATOR

ALZT-OP1a

Intervention Type DRUG

1\) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory

Placebo ALZT-OP1b

Intervention Type OTHER

Non-active tablets

Group II

ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration.

Group Type ACTIVE_COMPARATOR

ALZT-OP1a

Intervention Type DRUG

1\) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory

ALZT-OP1b

Intervention Type DRUG

Anti-inflammatory

Group III

ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration.

Group Type ACTIVE_COMPARATOR

ALZT-OP1b

Intervention Type DRUG

Anti-inflammatory

Placebo ALZT-OP1a

Intervention Type OTHER

Non-active capsules

Group IV

ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration.

Group Type PLACEBO_COMPARATOR

Placebo ALZT-OP1a

Intervention Type OTHER

Non-active capsules

Placebo ALZT-OP1b

Intervention Type OTHER

Non-active tablets

Interventions

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ALZT-OP1a

1\) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory

Intervention Type DRUG

ALZT-OP1b

Anti-inflammatory

Intervention Type DRUG

Placebo ALZT-OP1a

Non-active capsules

Intervention Type OTHER

Placebo ALZT-OP1b

Non-active tablets

Intervention Type OTHER

Other Intervention Names

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Cromolyn Ibuprofen

Eligibility Criteria

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Inclusion Criteria

* 55-79 years old;
* ≥ 8 years of education;
* Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol;
* Evidence of early AD, as defined by all of the following:

1. Memory complaint by subject or study partner that is verified by a study partner;
2. Objective memory impairment for age, documented by scoring below the education adjusted cutoff of the Logical Memory II subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale Third Edition (the maximum score is 25):

* ≤ 8 for 16 or more years of education, or
* ≤ 4 for 8-15 years of education;
* Essentially preserved general cognitive function;
* Largely intact functional activities;
* Not demented;
* Cerebrospinal fluid (CSF) biomarker results consistent with early AD, including CSF Aβ-42 levels ≥ 180 pg/mL and ≤ 690 pg/mL;
* Clinical Dementia Rating (Global) = 0.5; Memory Box score must be at least 0.5;
* Must be fluent in the language of the cognitive testing material being administered;
* Stability of permitted medications for 4 weeks prior to study start; subjects receiving acetylcholinesterase inhibitors and/or memantine should be on stable dose of those medications for at least 12 weeks prior to study start with every effort to maintain stable dose for the duration of the study;
* Visual and auditory acuity adequate for neuropsychological testing;
* Good general health with no diseases expected to interfere with the study;
* Must provide written informed consent for APOe4 genotype testing;
* Must provide written informed consent for CSF sampling.

Exclusion Criteria

* Any significant neurological disease other than suspected incipient AD, such as Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities;
* Major depressive episode, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) within the past 6 months, which could lead to difficulty complying with the protocol;
* History of schizophrenia or bipolar disorder (DSM-IV criteria);
* History of alcohol or substance abuse or dependence within the past 3 years (DSM-IV criteria);
* Currently taking medications that could lead to difficulty complying with the protocol; subjects must be on a stable dose of current medications for 4 weeks prior to study entry, with the exception of acetylcholinesterase inhibitors and/or memantine, which must be on a stable dose for at least 12 weeks prior to study entry;
* Investigational agents are prohibited one month prior to entry and for the duration of the trial;
* Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
* Currently taking cromolyn, or have taken cromolyn, within the past 12 months;
* Chronic daily use of high-dose NSAID for osteoarthritis, rheumatoid arthritis, or other chronic inflammatory diseases ("chronic" defined as 3200 mg/day for \>2 weeks);
* Chronic daily use of aspirin exceeding standard of care guidelines for low dose aspirin therapy for prevention of stroke and/or other recommended uses;
* Allergy to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®, etc.);
* Allergies to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin;
* Clinically significant respiratory disorders with impaired respiratory effort or difficulty taking inhaled drugs;
* Uncontrolled chronic asthma;
* Abnormal pulmonary function test, defined for this protocol as: FEV1/FVC \< predicted value for subject AND FEV1 \< 70% of predicted value, indicating moderate or severe respiratory obstruction;
* Taking inhaled protein products on a chronic basis;
* Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol;
* Pregnancy or lactation for female subjects of child-bearing potential (i.e., \< two years post-menopausal or not surgically sterile);
* For sexually active male subjects, unwillingness or incapability of using appropriate contraception methods;
* Severe renal or hepatic impairment.
Minimum Eligible Age

55 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PharmaConsulting Group

UNKNOWN

Sponsor Role collaborator

KCAS Bio

UNKNOWN

Sponsor Role collaborator

APCER Life Sciences

UNKNOWN

Sponsor Role collaborator

AZTherapies, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David R. Elmaleh, PhD

Role: STUDY_DIRECTOR

AZTherapies, Inc.

Locations

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Cognitive Clinical Trials

Gilbert, Arizona, United States

Site Status

Xenoscience

Phoenix, Arizona, United States

Site Status

Cognitive Clinical Trials

Scottsdale, Arizona, United States

Site Status

Territory Neurology & Research Institute

Tucson, Arizona, United States

Site Status

Alliance Research Center

Laguna Hills, California, United States

Site Status

Renew Behavioral Health

Long Beach, California, United States

Site Status

Excell Research, Inc.

Oceanside, California, United States

Site Status

University of California Irvine School of Medicine

Orange, California, United States

Site Status

Asclepes Research Center

Panorama City, California, United States

Site Status

Artemis Clinical Research

Riverside, California, United States

Site Status

CITrials

Riverside, California, United States

Site Status

Northern California Research

Sacramento, California, United States

Site Status

Syrentys Clinical Research

Santa Ana, California, United States

Site Status

Mile High Research Center

Denver, Colorado, United States

Site Status

TOPAZ Clinical Research

Apopka, Florida, United States

Site Status

Parkinson's Disease & Movement Disorders Center of Boca Raton

Boca Raton, Florida, United States

Site Status

Bradenton Research Center

Bradenton, Florida, United States

Site Status

Finlay Medical Research Group

Greenacres City, Florida, United States

Site Status

Galiz Clinical Research

Hialeah, Florida, United States

Site Status

The Neurology Research Group

Miami, Florida, United States

Site Status

Premier Clinical Research Institute

Miami, Florida, United States

Site Status

Finlay Medical Research Group

Miami, Florida, United States

Site Status

Next Phase Research Alliance - Cano Health

Miami, Florida, United States

Site Status

IMIC, Inc.

Miami, Florida, United States

Site Status

Next Phase Research Alliance - MetroMed

Miami, Florida, United States

Site Status

Next Phase Research Alliance

Miami, Florida, United States

Site Status

Panax

Miami Lakes, Florida, United States

Site Status

CNS Healthcare

Orlando, Florida, United States

Site Status

Pines Care Research Center

Pembroke Pines, Florida, United States

Site Status

Neurostudies, Inc.

Port Charlotte, Florida, United States

Site Status

Progressive Medical Research

Port Orange, Florida, United States

Site Status

Axiom Clinical Research

Tampa, Florida, United States

Site Status

Stedman Clinical Trials

Tampa, Florida, United States

Site Status

Columbus Research & Wellness Institute

Columbus, Georgia, United States

Site Status

Behavioral Health Care Associates

Schaumburg, Illinois, United States

Site Status

Eastern Maine Medical Center

Bangor, Maine, United States

Site Status

Coastal Health Care

Freeport, Maine, United States

Site Status

Samuel and Alexia Bratton Memory Clinic

Easton, Maryland, United States

Site Status

ActivMed Practices & Research, Inc.

Methuen, Massachusetts, United States

Site Status

The Alzheimer's Disease Center

Quincy, Massachusetts, United States

Site Status

Bronson Neurobehavioral Health

Paw Paw, Michigan, United States

Site Status

Cognitive Clinical Trials

Bellevue, Nebraska, United States

Site Status

Cognitive Clinical Trials

Omaha, Nebraska, United States

Site Status

ActivMed Practices & Research Inc.

Portsmouth, New Hampshire, United States

Site Status

Memory Enhancement Center of America

Eatontown, New Jersey, United States

Site Status

AdvancedMed Research

Lawrenceville, New Jersey, United States

Site Status

The NeuroCognitive Institute

Mount Arlington, New Jersey, United States

Site Status

Albuquerque Neuroscience

Albuquerque, New Mexico, United States

Site Status

Adirondack Medical Research Center

Glens Falls, New York, United States

Site Status

Manhattan Behavioral Medicine

New York, New York, United States

Site Status

Medical Research Network

New York, New York, United States

Site Status

Nathan S. Kline Institute for Psychiatric Research

New York, New York, United States

Site Status

Winifred Masterson Burke Medical Research Institute

White Plains, New York, United States

Site Status

ANI Neurology, PLLC Alzheimer's Memory Center

Charlotte, North Carolina, United States

Site Status

Raleigh Neurological Associates

Raleigh, North Carolina, United States

Site Status

PMG Winston-Salem

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

Insight Clincial Trials

Shaker Heights, Ohio, United States

Site Status

Cutting Edge Research Group

Oklahoma City, Oklahoma, United States

Site Status

Tulsa Clinical Research, Inc.

Tulsa, Oklahoma, United States

Site Status

Pearl Clinical Research

Norristown, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

Palmetto Health

Columbia, South Carolina, United States

Site Status

Metrolina Neurological Associates, PA

Rock Hill, South Carolina, United States

Site Status

CNS Healthcare

Memphis, Tennessee, United States

Site Status

Neurology Associates of Arlington, P.A.

Mansfield, Texas, United States

Site Status

Grayline Clinical Drug Trials

Wichita Falls, Texas, United States

Site Status

Wasatch Clinical Research, LLC

Salt Lake City, Utah, United States

Site Status

Kingfisher Cooperative

Spokane, Washington, United States

Site Status

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, Australia

Site Status

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales, Australia

Site Status

Pacific Private Clinic

Southport, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

Geelong Private Medical Centre

Geelong, Victoria, Australia

Site Status

Austin Health

Heidelberg, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

UMBAL "Dr. Georgi Stranski" EAD

Pleven, , Bulgaria

Site Status

MHAT "Central Onco Hospital" Ltd.

Plovdiv, , Bulgaria

Site Status

MBAL Ruse AD

Rousse, , Bulgaria

Site Status

"First MHAT - Sofia" EAD

Sofia, , Bulgaria

Site Status

University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD

Sofia, , Bulgaria

Site Status

Medical Arts Health Research

Penticton, British Columbia, Canada

Site Status

Medical Arts Health Research

West Vancouver, British Columbia, Canada

Site Status

Okanagan Clinical Trials

Kelowna, Britsh Columbia, Canada

Site Status

Montreal Neurological Research Institute

Québec, Montreal, Canada

Site Status

True North Clinical Research

Halifax, Nova Scotia, Canada

Site Status

True North Clinical Research

Kentville, Nova Scotia, Canada

Site Status

JBN Medical

Burlington, Ontario, Canada

Site Status

Chatham-Kent Clinical Trials

Chatham, Ontario, Canada

Site Status

The Centre for Memory and Aging

East York, Ontario, Canada

Site Status

Cliniuqe de la Memoire de l'Outouais

Gatineau, Quebec, Canada

Site Status

Neurosanatio, s.r.o.

Litomyšl, Czech Republic, Czechia

Site Status

Neurologie MU - Ondrej Koci, s.r.o.

Nový Bor, Czech Republic, Czechia

Site Status

CT Center MaVfe, s.r.o

Olomouc, Czech Republic, Czechia

Site Status

Vestra Clinics, s.r.o.

Rychnov nad Kněžnou, Czech Republic, Czechia

Site Status

NEUROHK, s.r.o.

Choceň, , Czechia

Site Status

Clinline Services s.r.o.

Hostivice, , Czechia

Site Status

Psychiatricka ambulance

Hradec Králové, , Czechia

Site Status

Psychiatricka ambulance Supervize s.r.o.

Kutná Hora, , Czechia

Site Status

Krajska nemocnice Liberec a.s.

Liberec, , Czechia

Site Status

A-shine, s.r.o.

Pilsen, , Czechia

Site Status

Clintrial.s.r.o.

Prague, , Czechia

Site Status

Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol

Prague, , Czechia

Site Status

INEP medical s.r.o.

Prague, , Czechia

Site Status

Neurologia Klinika Semmelweis Egyetem

Budapest, , Hungary

Site Status

Orszagos Klinikai Idegtudomanyi Intezat

Budapest, , Hungary

Site Status

Vaszary Kolos Korhaz

Esztergom, , Hungary

Site Status

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Site Status

Bekes Megyei Pandy Kalman Korhaz

Gyula, , Hungary

Site Status

Cermed Pawel Hernik

Bialystok, , Poland

Site Status

Podlaskie Centrum Psychogeriatrii

Bialystok, , Poland

Site Status

Przychondnia Srodmiescie

Bydgoszcz, , Poland

Site Status

Centrum Medyczne KERMED

Bydgoszcz, , Poland

Site Status

Szpital Powiatowy w Czeladzi

Czeladź, , Poland

Site Status

Centrum Zdrowia Psychicznego Biomed - Jan Latala

Kielce, , Poland

Site Status

Centrum Medyczne Plejady

Krakow, , Poland

Site Status

Centrum Opieki Zdrowotnej Orkan-Med

Ksawerów, , Poland

Site Status

Centrum Medyczne im. Dr Karola Jonschera w Lodzi

Lodz, , Poland

Site Status

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, , Poland

Site Status

CRC Sp. Zo.o.

Poznan, , Poland

Site Status

Euromedis Sp. Zo.o

Szczecin, , Poland

Site Status

Countries

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United States Australia Bulgaria Canada Czechia Hungary Poland

Other Identifiers

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AZT-001

Identifier Type: -

Identifier Source: org_study_id