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

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

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).

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: ALZT-OP1a; Other: Placebo ALZT-OP1b; Drug: ALZT-OP1b; Other: Placebo ALZT-OP1a

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 620
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Macquarie Park, New South Wales, Australia, 2113
      • KaRa Institute of Neurological Diseases
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Pacific Private Clinic
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Geelong Private Medical Centre
    • Heidelberg, Victoria, Australia, 3081
      • Austin Health
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMBAL "Dr. Georgi Stranski" EAD
  • Plovdiv, Bulgaria, 4000
    • MHAT "Central Onco Hospital" Ltd.
  • Ruse, Bulgaria, 7002
    • MBAL Ruse AD
  • Sofia, Bulgaria, 1154
    • "First MHAT - Sofia" EAD
  • Sofia, Bulgaria, 1431
    • University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD
• Canada
  • British Columbia
    • Penticton, British Columbia, Canada, V2A 5L5
      • Medical Arts Health Research
    • West Vancouver, British Columbia, Canada, V7T 1C5
      • Medical Arts Health Research
  • Britsh Columbia
    • Kelowna, Britsh Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials
  • Montreal
    • Québec, Montreal, Canada, H3A 284
      • Montreal Neurological Research Institute
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1M7
      • True North Clinical Research
    • Kentville, Nova Scotia, Canada, B4N 4K9
      • True North Clinical Research
  • Ontario
    • Burlington, Ontario, Canada, L7M 4Y1
      • JBN Medical
    • Chatham, Ontario, Canada, N7l1C1
      • Chatham-Kent Clinical Trials
    • East York, Ontario, Canada, M4G 3E8
      • The Centre for Memory and Aging
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Cliniuqe de la Memoire de l'Outouais
• Czechia
  • Chocen, Czechia, 565 01
    • NEUROHK, s.r.o.
  • Hostivice, Czechia, 253 01
    • Clinline Services s.r.o.
  • Hradec Kralove, Czechia, 503 41
    • Psychiatricka ambulance
  • Kutná Hora, Czechia, 28401
    • Psychiatricka ambulance Supervize s.r.o.
  • Liberec, Czechia, 460 63
    • Krajská nemocnice Liberec a.s.
  • Plzen, Czechia, 312 00
    • A-Shine, s.r.o.
  • Praha, Czechia, 100 00
    • Clintrial.s.r.o.
  • Praha, Czechia, 150 06
    • Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol
  • Praha, Czechia, 186 00
    • INEP medical s.r.o.
  • Czech Republic
    • Litomyšl, Czech Republic, Czechia, 570 01
      • Neurosanatio, s.r.o.
    • Novy Bor, Czech Republic, Czechia, 473 01
      • Neurologie MU - Ondrej Koci, s.r.o.
    • Olomouc, Czech Republic, Czechia, 779 00
      • CT Center MaVfe, s.r.o
    • Rychnov Nad Kněžnou, Czech Republic, Czechia, 516 01
      • Vestra Clinics, s.r.o.
• Hungary
  • Budapest, Hungary, H-1083
    • Neurologia Klinika Semmelweis Egyetem
  • Budapest, Hungary, H-1145
    • Orszagos Klinikai Idegtudomanyi Intezat
  • Esztergom, Hungary, H-2500
    • Vaszary Kolos Kórház
  • Gyula, Hungary, H-5700
    • Bekes Megyei Pandy Kalman Korhaz
  • Győr, Hungary, 09024
    • Petz Aladar Megyei Oktato Korhaz
• Poland
  • Bialystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Bialystok, Poland, 15-270
    • Cermed Pawel Hernik
  • Bydgoszcz, Poland, 85-231
    • Centrum Medyczne KerMed
  • Bydgoszcz, Poland, 85-080
    • Przychondnia Srodmiescie
  • Czeladz, Poland, 41-250
    • Szpital Powiatowy w Czeladzi
  • Kielce, Poland, 25-411
    • Centrum Zdrowia Psychicznego Biomed - Jan Latala
  • Kraków, Poland, 30-363
    • Centrum Medyczne Plejady
  • Ksawerow, Poland, 95-054
    • Centrum Opieki Zdrowotnej Orkan-Med
  • Lodz, Poland, 93-113
    • Centrum Medyczne im. Dr Karola Jonschera w Lodzi
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
  • Poznan, Poland, 60-856
    • CRC Sp. Zo.o.
  • Szczecin, Poland, 70-111
    • Euromedis Sp. Zo.o
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85296
      • Cognitive Clinical Trials
    • Phoenix, Arizona, United States, 85004
      • Xenoscience
    • Scottsdale, Arizona, United States, 85251
      • Cognitive Clinical Trials
    • Tucson, Arizona, United States, 85704
      • Territory Neurology & Research Institute
  • California
    • Laguna Hills, California, United States, 92653
      • Alliance Research Center
    • Long Beach, California, United States, 90807
      • Renew Behavioral Health
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • Orange, California, United States, 92868
      • University of California Irvine School of Medicine
    • Panorama City, California, United States, 91402
      • ASCLEPES Research Center
    • Riverside, California, United States, 92506
      • CiTrials
    • Riverside, California, United States, 92503
      • Artemis Clinical Research
    • Sacramento, California, United States, 95821
      • Northern California Research
    • Santa Ana, California, United States, 92705
      • Syrentys Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80218
      • Mile High Research Center
  • Florida
    • Apopka, Florida, United States, 32703
      • Topaz Clinical Research
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease & Movement Disorders Center of Boca Raton
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research Group
    • Hialeah, Florida, United States, 33016
      • Galiz Clinical Research
    • Miami, Florida, United States, 33122
      • Premier Clinical Research Institute
    • Miami, Florida, United States, 22176
      • The Neurology Research Group
    • Miami, Florida, United States, 33126
      • Finlay Medical Research Group
    • Miami, Florida, United States, 33144
      • Next Phase Research Alliance - Cano Health
    • Miami, Florida, United States, 33157
      • IMIC, Inc.
    • Miami, Florida, United States, 33186
      • Next Phase Research Alliance - MetroMed
    • Miami, Florida, United States, 33186
      • Next Phase Research Alliance
    • Miami Lakes, Florida, United States, 33014
      • PANAX
    • Orlando, Florida, United States, 32801
      • CNS Healthcare
    • Pembroke Pines, Florida, United States, 33026
      • Pines Care Research Center
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies, Inc.
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Research & Wellness Institute
  • Illinois
    • Schaumburg, Illinois, United States, 60193
      • Behavioral Health Care Associates
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center
    • Freeport, Maine, United States, 04032
      • Coastal Health Care
  • Maryland
    • Easton, Maryland, United States, 21601
      • Samuel and Alexia Bratton Memory Clinic
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc.
    • Quincy, Massachusetts, United States, 02169
      • The Alzheimer's Disease Center
  • Michigan
    • Paw Paw, Michigan, United States, 49079
      • Bronson Neurobehavioral Health
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Cognitive Clinical Trials
    • Omaha, Nebraska, United States, 68007
      • Cognitive Clinical Trials
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed Practices & Research Inc.
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America
    • Lawrenceville, New Jersey, United States, 08648
      • AdvancedMed Research
    • Mount Arlington, New Jersey, United States, 07856
      • The NeuroCognitive Institute
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience
  • New York
    • Glens Falls, New York, United States, 12801
      • Adirondack Medical Research Center
    • New York, New York, United States, 10128
      • Medical Research Network
    • New York, New York, United States, 10023
      • Manhattan Behavioral Medicine
    • New York, New York, United States, 10128
      • Nathan S. Kline Institute for Psychiatric Research
    • White Plains, New York, United States, 10605
      • Winifred Masterson Burke Medical Research Institute
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • ANI Neurology, PLLC Alzheimer's Memory Center
    • Raleigh, North Carolina, United States, 27607
      • Raleigh Neurological Associates
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Winston-Salem
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
    • Shaker Heights, Ohio, United States, 44122
      • Insight Clincial Trials
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
    • Tulsa, Oklahoma, United States, 74114
      • Tulsa Clinical Research, Inc.
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19401
      • Pearl Clinical Research
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Columbia, South Carolina, United States, 29044
      • Palmetto Health
    • Rock Hill, South Carolina, United States, 29732
      • Metrolina Neurological Associates, PA
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • CNS Healthcare
  • Texas
    • Mansfield, Texas, United States, 76063
      • Neurology Associates of Arlington, P.A.
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Wasatch Clinical Research, LLC
  • Washington
    • Spokane, Washington, United States, 99202
      • Kingfisher Cooperative

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I; ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.	Drug: ALZT-OP1a; 1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory; Other Names: Cromolyn; Other: Placebo ALZT-OP1b; Non-active tablets
Active Comparator: Group II; ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration.	Drug: ALZT-OP1a; 1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory; Other Names: Cromolyn; Drug: ALZT-OP1b; Anti-inflammatory; Other Names: Ibuprofen
Active Comparator: Group III; ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration.	Drug: ALZT-OP1b; Anti-inflammatory; Other Names: Ibuprofen; Other: Placebo ALZT-OP1a; Non-active capsules
Placebo Comparator: Group IV; ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration.	Other: Placebo ALZT-OP1b; Non-active tablets; Other: Placebo ALZT-OP1a; Non-active capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAE)	Safety will be evaluated based on the number, type, and frequency of treatment emergent adverse events. They will be individually presented for all subjects in data listings, and summarized in tables by treatment group and by treatment assignment. The AE's will be summarized and reported collectively based on information obtained through physical examination, ECG, and laboratory findings captured after dosing is initiated.	72 weeks

Collaborators and Investigators

• Sponsor: AZTherapies, Inc.
• Collaborators: APCER Life Sciences; PharmaConsulting Group; KCAS Bio
• Investigators: Study Director: David R. Elmaleh, PhD, AZTherapies, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2015
• Primary Completion (Actual): November 13, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: September 10, 2015
• First Submitted That Met QC Criteria: September 10, 2015
• First Posted (Estimate): September 11, 2015

Study Record Updates

• Last Update Posted (Actual): November 10, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: MCI; Aging; Memory problems; Memory loss; Early AD; aMCI; Early Alzheimer's Disease; Early stage AD; prodromal
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: AZT-001