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

NCT02547818 | Completed Phase 3 DMC

• 1 other identifier: AZT-001
• Study Type: interventional
• Target: 620
• Locations: 7 countries
• Sites: 121

Brief Summary

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).

Conditions

Alzheimer's Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Clinical Dementia Rating-Sum of Boxes (CDR-SB)

  The combination active treatment group will be compared to each of the single component groups, including the placebo group, the mean change from Baseline to Week 72 will be quantified.

  Baseline and Week 72

Secondary Outcomes (1)

• Number of Treatment Emergent Adverse Events (TEAE)

  72 weeks

Study Arms (4)

Group I

ACTIVE COMPARATOR

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

Drug: ALZT-OP1a; Other: Placebo ALZT-OP1b

Group II

ACTIVE COMPARATOR

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

Drug: ALZT-OP1a; Drug: ALZT-OP1b

Group III

ACTIVE COMPARATOR

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

Drug: ALZT-OP1b; Other: Placebo ALZT-OP1a

Group IV

PLACEBO COMPARATOR

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

Other: Placebo ALZT-OP1a; Other: Placebo ALZT-OP1b

Interventions

ALZT-OP1a DRUG

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

Also known as: Cromolyn

Group I; Group II

ALZT-OP1b DRUG

Anti-inflammatory

Also known as: Ibuprofen

Group II; Group III

Placebo ALZT-OP1a OTHER

Non-active capsules

Group III; Group IV

Placebo ALZT-OP1b OTHER

Non-active tablets

Group I; Group IV

Eligibility Criteria

• Age: 55 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Memory complaint by subject or study partner that is verified by a study partner;
• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• AZTherapies, Inc.: lead
• PharmaConsulting Group: collaborator
• KCAS Bio: collaborator
• APCER Life Sciences: collaborator

Study Sites (121)

Cognitive Clinical Trials

Gilbert, Arizona, 85296, United States

Location

Xenoscience

Phoenix, Arizona, 85004, United States

Location

Cognitive Clinical Trials

Scottsdale, Arizona, 85251, United States

Location

Territory Neurology & Research Institute

Tucson, Arizona, 85704, United States

Location

Alliance Research Center

Laguna Hills, California, 92653, United States

Location

Renew Behavioral Health

Long Beach, California, 90807, United States

Location

Excell Research, Inc.

Oceanside, California, 92056, United States

Location

University of California Irvine School of Medicine

Orange, California, 92868, United States

Location

Asclepes Research Center

Panorama City, California, 91402, United States

Location

Artemis Clinical Research

Riverside, California, 92503, United States

Location

CITrials

Riverside, California, 92506, United States

Location

Northern California Research

Sacramento, California, 95821, United States

Location

Syrentys Clinical Research

Santa Ana, California, 92705, United States

Location

Mile High Research Center

Denver, Colorado, 80218, United States

Location

TOPAZ Clinical Research

Apopka, Florida, 32703, United States

Location

Parkinson's Disease & Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

Finlay Medical Research Group

Greenacres City, Florida, 33467, United States

Location

Galiz Clinical Research

Hialeah, Florida, 33016, United States

Location

The Neurology Research Group

Miami, Florida, 22176, United States

Location

Premier Clinical Research Institute

Miami, Florida, 33122, United States

Location

Finlay Medical Research Group

Miami, Florida, 33126, United States

Location

Next Phase Research Alliance - Cano Health

Miami, Florida, 33144, United States

Location

IMIC, Inc.

Miami, Florida, 33157, United States

Location

Next Phase Research Alliance - MetroMed

Miami, Florida, 33186, United States

Location

Next Phase Research Alliance

Miami, Florida, 33186, United States

Location

Panax

Miami Lakes, Florida, 33014, United States

Location

CNS Healthcare

Orlando, Florida, 32801, United States

Location

Pines Care Research Center

Pembroke Pines, Florida, 33026, United States

Location

Neurostudies, Inc.

Port Charlotte, Florida, 33952, United States

Location

Progressive Medical Research

Port Orange, Florida, 32127, United States

Location

Axiom Clinical Research

Tampa, Florida, 33609, United States

Location

Stedman Clinical Trials

Tampa, Florida, 33613, United States

Location

Columbus Research & Wellness Institute

Columbus, Georgia, 31904, United States

Location

Behavioral Health Care Associates

Schaumburg, Illinois, 60193, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Coastal Health Care

Freeport, Maine, 04032, United States

Location

Samuel and Alexia Bratton Memory Clinic

Easton, Maryland, 21601, United States

Location

ActivMed Practices & Research, Inc.

Methuen, Massachusetts, 01844, United States

Location

The Alzheimer's Disease Center

Quincy, Massachusetts, 02169, United States

Location

Bronson Neurobehavioral Health

Paw Paw, Michigan, 49079, United States

Location

Cognitive Clinical Trials

Bellevue, Nebraska, 68005, United States

Location

Cognitive Clinical Trials

Omaha, Nebraska, 68007, United States

Location

ActivMed Practices & Research Inc.

Portsmouth, New Hampshire, 03801, United States

Location

Memory Enhancement Center of America

Eatontown, New Jersey, 07724, United States

Location

AdvancedMed Research

Lawrenceville, New Jersey, 08648, United States

Location

The NeuroCognitive Institute

Mount Arlington, New Jersey, 07856, United States

Location

Albuquerque Neuroscience

Albuquerque, New Mexico, 87109, United States

Location

Adirondack Medical Research Center

Glens Falls, New York, 12801, United States

Location

Manhattan Behavioral Medicine

New York, New York, 10023, United States

Location

Medical Research Network

New York, New York, 10128, United States

Location

Nathan S. Kline Institute for Psychiatric Research

New York, New York, 10128, United States

Location

Winifred Masterson Burke Medical Research Institute

White Plains, New York, 10605, United States

Location

ANI Neurology, PLLC Alzheimer's Memory Center

Charlotte, North Carolina, 28270, United States

Location

Raleigh Neurological Associates

Raleigh, North Carolina, 27607, United States

Location

PMG Winston-Salem

Winston-Salem, North Carolina, 27103, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Insight Clincial Trials

Shaker Heights, Ohio, 44122, United States

Location

Cutting Edge Research Group

Oklahoma City, Oklahoma, 73116, United States

Location

Tulsa Clinical Research, Inc.

Tulsa, Oklahoma, 74114, United States

Location

Pearl Clinical Research

Norristown, Pennsylvania, 19401, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Palmetto Health

Columbia, South Carolina, 29044, United States

Location

Metrolina Neurological Associates, PA

Rock Hill, South Carolina, 29732, United States

Location

CNS Healthcare

Memphis, Tennessee, 38119, United States

Location

Neurology Associates of Arlington, P.A.

Mansfield, Texas, 76063, United States

Location

Grayline Clinical Drug Trials

Wichita Falls, Texas, 76309, United States

Location

Wasatch Clinical Research, LLC

Salt Lake City, Utah, 84107, United States

Location

Kingfisher Cooperative

Spokane, Washington, 99202, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

KaRa Institute of Neurological Diseases

Macquarie Park, New South Wales, 2113, Australia

Location

Pacific Private Clinic

Southport, Queensland, 4215, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Geelong Private Medical Centre

Geelong, Victoria, 3220, Australia

Location

Austin Health

Heidelberg, Victoria, 3081, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

UMBAL "Dr. Georgi Stranski" EAD

Pleven, 5800, Bulgaria

Location

MHAT "Central Onco Hospital" Ltd.

Plovdiv, 4000, Bulgaria

Location

MBAL Ruse AD

Rousse, 7002, Bulgaria

Location

"First MHAT - Sofia" EAD

Sofia, 1154, Bulgaria

Location

University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD

Sofia, 1431, Bulgaria

Location

Medical Arts Health Research

Penticton, British Columbia, V2A 5L5, Canada

Location

Medical Arts Health Research

West Vancouver, British Columbia, V7T 1C5, Canada

Location

Okanagan Clinical Trials

Kelowna, Britsh Columbia, V1Y 1Z9, Canada

Location

Montreal Neurological Research Institute

Québec, Montreal, H3A 284, Canada

Location

True North Clinical Research

Halifax, Nova Scotia, B3S 1M7, Canada

Location

True North Clinical Research

Kentville, Nova Scotia, B4N 4K9, Canada

Location

JBN Medical

Burlington, Ontario, L7M 4Y1, Canada

Location

Chatham-Kent Clinical Trials

Chatham, Ontario, N7l1C1, Canada

Location

The Centre for Memory and Aging

East York, Ontario, M4G 3E8, Canada

Location

Cliniuqe de la Memoire de l'Outouais

Gatineau, Quebec, J8T 8J1, Canada

Location

Neurosanatio, s.r.o.

Litomyšl, Czech Republic, 570 01, Czechia

Location

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

Nový Bor, Czech Republic, 473 01, Czechia

Location

CT Center MaVfe, s.r.o

Olomouc, Czech Republic, 779 00, Czechia

Location

Vestra Clinics, s.r.o.

Rychnov nad Kněžnou, Czech Republic, 516 01, Czechia

Location

NEUROHK, s.r.o.

Choceň, 565 01, Czechia

Location

Clinline Services s.r.o.

Hostivice, 253 01, Czechia

Location

Psychiatricka ambulance

Hradec Králové, 503 41, Czechia

Location

Psychiatricka ambulance Supervize s.r.o.

Kutná Hora, 28401, Czechia

Location

Krajska nemocnice Liberec a.s.

Liberec, 460 63, Czechia

Location

A-shine, s.r.o.

Pilsen, 312 00, Czechia

Location

Clintrial.s.r.o.

Prague, 100 00, Czechia

Location

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

Prague, 150 06, Czechia

Location

INEP medical s.r.o.

Prague, 186 00, Czechia

Location

Neurologia Klinika Semmelweis Egyetem

Budapest, H-1083, Hungary

Location

Orszagos Klinikai Idegtudomanyi Intezat

Budapest, H-1145, Hungary

Location

Vaszary Kolos Korhaz

Esztergom, H-2500, Hungary

Location

Petz Aladar Megyei Oktato Korhaz

Győr, 09024, Hungary

Location

Bekes Megyei Pandy Kalman Korhaz

Gyula, H-5700, Hungary

Location

Cermed Pawel Hernik

Bialystok, 15-270, Poland

Location

Podlaskie Centrum Psychogeriatrii

Bialystok, 15-756, Poland

Location

Przychondnia Srodmiescie

Bydgoszcz, 85-080, Poland

Location

Centrum Medyczne KERMED

Bydgoszcz, 85-231, Poland

Location

Szpital Powiatowy w Czeladzi

Czeladź, 41-250, Poland

Location

Centrum Zdrowia Psychicznego Biomed - Jan Latala

Kielce, 25-411, Poland

Location

Centrum Medyczne Plejady

Krakow, 30-363, Poland

Location

Centrum Opieki Zdrowotnej Orkan-Med

Ksawerów, 95-054, Poland

Location

Centrum Medyczne im. Dr Karola Jonschera w Lodzi

Lodz, 93-113, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie

Lublin, 20-954, Poland

Location

CRC Sp. Zo.o.

Poznan, 60-856, Poland

Location

Euromedis Sp. Zo.o

Szczecin, 70-111, Poland

Location

MeSH Terms

Conditions

Alzheimer Disease; Memory Disorders

Interventions

Cromolyn Sodium; Ibuprofen

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• David R. Elmaleh, PhD

  AZTherapies, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2015
• First Posted: September 11, 2015
• Study Start: September 15, 2015
• Primary Completion: November 13, 2020
• Study Completion: November 18, 2020
• Last Updated: November 10, 2021

Record last verified: 2020-11

Locations

PL (12); BU (5); CA (10); HU (5); US (69); AU (7); CZ (13)