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

Study Description

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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).

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Drug: ALZT-OP1a; Drug: ALZT-OP1b; Other: Placebo ALZT-OP1a; Other: Placebo ALZT-OP1b	Phase 3

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	600 participants
Allocation:	Randomized
Intervention Model:	Factorial Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	A Phase III Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Study Start Date :	September 2015
Estimated Primary Completion Date :	November 2019
Estimated Study Completion Date :	November 2019

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Group I; ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.	Drug: ALZT-OP1a; AB polymerization inhibitor; Other Name: 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; AB polymerization inhibitor; Other Name: Cromolyn; Drug: ALZT-OP1b; Anti-inflammatory; Other Name: 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 Name: 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-OP1a; Non-active capsules; Other: Placebo ALZT-OP1b; Non-active tablets

Outcome Measures

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Primary Outcome Measures :

1. Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline and Week 72 ]
   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.

Secondary Outcome Measures :

1. Number of Treatment Emergent Adverse Events (TEAE) [ Time Frame: 72 weeks ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	55 Years to 79 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Contacts

Contact: David A. Brazier, BS	617-318-3428	david.brazier@aztherapies.com
Contact: David R. Elmaleh, PhD		delmaleh@aztherapies.com

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Locations

United States, Arizona
Xenoscience	Terminated
Phoenix, Arizona, United States, 85004
Territory Neurology & Research Institute	Recruiting
Tucson, Arizona, United States, 85704
United States, California
Alliance Research Center	Withdrawn
Laguna Hills, California, United States, 92653
Renew Behavioral Health	Withdrawn
Long Beach, California, United States, 90807
Excell Research, Inc.	Withdrawn
Oceanside, California, United States, 92056
University of California Irvine School of Medicine	Withdrawn
Orange, California, United States, 92868
Asclepes Research Center	Withdrawn
Panorama City, California, United States, 91402
CITrials	Recruiting
Riverside, California, United States, 92506
Northern California Research	Recruiting
Sacramento, California, United States, 95821
Syrentys Clinical Research	Recruiting
Santa Ana, California, United States, 92705
United States, Colorado
Mile High Research Center	Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Parkinson's Disease & Movement Disorders Center of Boca Raton	Recruiting
Boca Raton, Florida, United States, 33486
Bradenton Research Center	Recruiting
Bradenton, Florida, United States, 34205
Panax	Withdrawn
Miami Lakes, Florida, United States, 33014
The Neurology Research Group	Recruiting
Miami, Florida, United States, 22176
Premier Clinical Research Institute	Recruiting
Miami, Florida, United States, 33122
IMIC, Inc.	Recruiting
Miami, Florida, United States, 33157
CNS Healthcare	Recruiting
Orlando, Florida, United States, 32801
Neurostudies, Inc.	Withdrawn
Port Charlotte, Florida, United States, 33952
Progressive Medical Research	Recruiting
Port Orange, Florida, United States, 32127
Stedman Clinical Trials	Withdrawn
Tampa, Florida, United States, 33613
United States, Georgia
Columbus Research & Wellness Institute	Withdrawn
Columbus, Georgia, United States, 31904
United States, Illinois
Behavioral Health Care Associates	Withdrawn
Schaumburg, Illinois, United States, 60193
United States, Maine
Eastern Maine Medical Center	Recruiting
Bangor, Maine, United States, 04401
Coastal Health Care	Recruiting
Freeport, Maine, United States, 04032
United States, Maryland
Samuel and Alexia Bratton Memory Clinic	Recruiting
Easton, Maryland, United States, 21601
United States, Massachusetts
ActivMed Practices & Research, Inc.	Recruiting
Methuen, Massachusetts, United States, 01844
United States, Michigan
Bronson Neurobehavioral Health	Recruiting
Paw Paw, Michigan, United States, 49079
United States, New Hampshire
ActivMed Practices & Research Inc.	Withdrawn
Portsmouth, New Hampshire, United States, 03801
United States, New Jersey
Memory Enhancement Center of America	Recruiting
Eatontown, New Jersey, United States, 07724
AdvancedMed Research	Withdrawn
Lawrenceville, New Jersey, United States, 08648
The NeuroCognitive Institute	Withdrawn
Mount Arlington, New Jersey, United States, 07856
United States, New Mexico
Albuquerque Neuroscience	Recruiting
Albuquerque, New Mexico, United States, 87109
United States, New York
Adirondack Medical Research Center	Recruiting
Glens Falls, New York, United States, 12801
Manhattan Behavioral Medicine	Recruiting
New York, New York, United States, 10023
Medical Research Network	Withdrawn
New York, New York, United States, 10128
Nathan S. Kline Institute for Psychiatric Research	Recruiting
New York, New York, United States, 10128
Winifred Masterson Burke Medical Research Institute	Recruiting
White Plains, New York, United States, 10605
United States, North Carolina
ANI Neurology, PLLC Alzheimer's Memory Center	Recruiting
Charlotte, North Carolina, United States, 28270
PMG Winston-Salem	Recruiting
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Insight Clincial Trials	Recruiting
Shaker Heights, Ohio, United States, 44122
United States, Oklahoma
Cutting Edge Research Group	Recruiting
Oklahoma City, Oklahoma, United States, 73116
Tulsa Clinical Research, Inc.	Withdrawn
Tulsa, Oklahoma, United States, 74114
United States, Pennsylvania
Pearl Clinical Research	Withdrawn
Norristown, Pennsylvania, United States, 19401
Thomas Jefferson University	Recruiting
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Metrolina Neurological Associates, PA	Recruiting
Rock Hill, South Carolina, United States, 29732
United States, Tennessee
CNS Healthcare	Recruiting
Memphis, Tennessee, United States, 38119
United States, Texas
Neurology Associates of Arlington, P.A.	Withdrawn
Mansfield, Texas, United States, 76063
Grayline Clinical Drug Trials	Withdrawn
Wichita Falls, Texas, United States, 76309
United States, Utah
Wasatch Clinical Research, LLC	Recruiting
Salt Lake City, Utah, United States, 84107
Australia, New South Wales
St Vincent's Hospital Sydney	Terminated
Darlinghurst, New South Wales, Australia, 2010
KaRa Institute of Neurological Diseases	Terminated
Macquarie Park, New South Wales, Australia, 2113
Australia, Queensland
Pacific Private Clinic	Terminated
Southport, Queensland, Australia, 4215
Australia, South Australia
Royal Adelaide Hospital	Terminated
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Geelong Private Medical Centre	Terminated
Geelong, Victoria, Australia, 3220
Austin Health	Terminated
Heidelberg, Victoria, Australia, 3081
Royal Melbourne Hospital	Terminated
Parkville, Victoria, Australia, 3050
Bulgaria
UMBAL "Dr. Georgi Stranski" EAD	Recruiting
Pleven, Bulgaria, 5800
MHAT "Central Onco Hospital" Ltd.	Recruiting
Plovdiv, Bulgaria, 4000
MBAL Ruse AD	Recruiting
Ruse, Bulgaria, 7002
"First MHAT - Sofia" EAD	Recruiting
Sofia, Bulgaria, 1154
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD	Withdrawn
Sofia, Bulgaria, 1431
Canada, Alberta
Heritage Medical Research Clinic, The University of Calgary	Recruiting
Calgary, Alberta, Canada, T2N 4Z6
Canada, Britsh Columbia
Okanagan Clinical Trials	Recruiting
Kelowna, Britsh Columbia, Canada, V1Y 1Z9
Canada, Ontario
Chatham-Kent Clinical Trials	Withdrawn
Chatam-Kent, Ontario, Canada, N7l1C1
The Centre for Memory and Aging	Recruiting
East York, Ontario, Canada, M4G 3E8
Czechia
Neurosanatio, s.r.o.	Recruiting
Litomyšl, Czech Republic, Czechia, 570 01
Neurologie MU - Ondrej Koci, s.r.o.	Recruiting
Novy Bor, Czech Republic, Czechia, 473 01
CT Center MaVfe, s.r.o	Recruiting
Olomouc, Czech Republic, Czechia, 779 00
Vestra Clinics, s.r.o.	Recruiting
Rychnov Nad Kněžnou, Czech Republic, Czechia, 516 01
NEUROHK, s.r.o.	Recruiting
Chocen, Czechia, 565 01
Clinline Services s.r.o.	Withdrawn
Hostivice, Czechia, 253 01
Psychiatricka ambulance	Recruiting
Hradec Kralove, Czechia, 503 41
Psychiatricka ambulance Supervize s.r.o.	Recruiting
Kutná Hora, Czechia, 28401
Krajska nemocnice Liberec a.s.	Withdrawn
Liberec, Czechia, 460 63
A-shine, s.r.o.	Recruiting
Plzen, Czechia, 312 00
Clintrial.s.r.o.	Recruiting
Praha, Czechia, 100 00
Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol	Recruiting
Praha, Czechia, 150 06
INEP medical s.r.o.	Recruiting
Praha, Czechia, 186 00
Hungary
Neurologia Klinika Semmelweis Egyetem	Recruiting
Budapest, Hungary, H-1083
Orszagos Klinikai Idegtudomanyi Intezat	Withdrawn
Budapest, Hungary, H-1145
Vaszary Kolos Korhaz	Recruiting
Esztergom, Hungary, H-2500
Bekes Megyei Pandy Kalman Korhaz	Withdrawn
Gyula, Hungary, H-5700
Petz Aladar Megyei Oktato Korhaz	Recruiting
Győr, Hungary, 09024
Poland
Cermed Pawel Hernik	Recruiting
Bialystok, Poland, 15-270
Podlaskie Centrum Psychogeriatrii	Recruiting
Bialystok, Poland, 15-756
Przychondnia Srodmiescie	Recruiting
Bydgoszcz, Poland, 85-080
Centrum Medyczne KERMED	Recruiting
Bydgoszcz, Poland, 85-231
Szpital Powiatowy w Czeladzi	Withdrawn
Czeladz, Poland, 41-250
Centrum Zdrowia Psychicznego Biomed - Jan Latala	Withdrawn
Kielce, Poland, 25-411
Centrum Medyczne Plejady	Recruiting
Kraków, Poland, 30-363
Centrum Opieki Zdrowotnej Orkan-Med	Recruiting
Ksawerow, Poland, 95-054
Centrum Medyczne im. Dr Karola Jonschera w Lodzi	Recruiting
Lodz, Poland, 93-113
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Recruiting
Lublin, Poland, 20-954
CRC Sp. Zo.o.	Recruiting
Poznan, Poland, 60-856
Euromedis Sp. Zo.o	Recruiting
Szczecin, Poland, 70-111

Sponsors and Collaborators

AZTherapies, Inc.

PharmaConsulting Group

KCAS Bio

APCER Life Sciences

Investigators

Study Director:	David R. Elmaleh, PhD	AZTherapies, Inc.

More Information

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Additional Information:

US Residents may click here to find out more about participation in this trial. 

Responsible Party:	AZTherapies, Inc.
ClinicalTrials.gov Identifier:	NCT02547818 History of Changes
Other Study ID Numbers:	AZT-001
First Posted:	September 11, 2015
Last Update Posted:	June 4, 2018
Last Verified:	June 2018

Keywords provided by AZTherapies, Inc.:

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

Additional relevant MeSH terms:

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