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

Alzheimer's Disease Clinical Trial

— COGNITE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02547818
• Other study ID #: AZT-001
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2015
• Est. completion date: November 18, 2020

Study information

• Verified date: November 2020
• Source: AZTherapies, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 620
• Est. completion date: November 18, 2020
• Est. primary completion date: November 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 79 Years

Eligibility

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 Aß-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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• ALZT-OP1a
1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory
• ALZT-OP1b
Anti-inflammatory

Other:
• Placebo ALZT-OP1a
Non-active capsules
• Placebo ALZT-OP1b
Non-active tablets

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Geelong Private Medical Centre	Geelong	Victoria
Australia	Austin Health	Heidelberg	Victoria
Australia	KaRa Institute of Neurological Diseases	Macquarie Park	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Pacific Private Clinic	Southport	Queensland
Bulgaria	UMBAL "Dr. Georgi Stranski" EAD	Pleven
Bulgaria	MHAT "Central Onco Hospital" Ltd.	Plovdiv
Bulgaria	MBAL Ruse AD	Ruse
Bulgaria	"First MHAT - Sofia" EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD	Sofia
Canada	JBN Medical	Burlington	Ontario
Canada	Chatham-Kent Clinical Trials	Chatham	Ontario
Canada	The Centre for Memory and Aging	East York	Ontario
Canada	Cliniuqe de la Memoire de l'Outouais	Gatineau	Quebec
Canada	True North Clinical Research	Halifax	Nova Scotia
Canada	Okanagan Clinical Trials	Kelowna	Britsh Columbia
Canada	True North Clinical Research	Kentville	Nova Scotia
Canada	Medical Arts Health Research	Penticton	British Columbia
Canada	Montreal Neurological Research Institute	Québec	Montreal
Canada	Medical Arts Health Research	West Vancouver	British Columbia
Czechia	NEUROHK, s.r.o.	Chocen
Czechia	Clinline Services s.r.o.	Hostivice
Czechia	Psychiatricka ambulance	Hradec Kralove
Czechia	Psychiatricka ambulance Supervize s.r.o.	Kutná Hora
Czechia	Krajska nemocnice Liberec a.s.	Liberec
Czechia	Neurosanatio, s.r.o.	Litomyšl	Czech Republic
Czechia	Neurologie MU - Ondrej Koci, s.r.o.	Novy Bor	Czech Republic
Czechia	CT Center MaVfe, s.r.o	Olomouc	Czech Republic
Czechia	A-shine, s.r.o.	Plzen
Czechia	Clintrial.s.r.o.	Praha
Czechia	Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol	Praha
Czechia	INEP medical s.r.o.	Praha
Czechia	Vestra Clinics, s.r.o.	Rychnov Nad Knežnou	Czech Republic
Hungary	Neurologia Klinika Semmelweis Egyetem	Budapest
Hungary	Orszagos Klinikai Idegtudomanyi Intezat	Budapest
Hungary	Vaszary Kolos Korhaz	Esztergom
Hungary	Petz Aladar Megyei Oktato Korhaz	Gyor
Hungary	Bekes Megyei Pandy Kalman Korhaz	Gyula
Poland	Cermed Pawel Hernik	Bialystok
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok
Poland	Centrum Medyczne KERMED	Bydgoszcz
Poland	Przychondnia Srodmiescie	Bydgoszcz
Poland	Szpital Powiatowy w Czeladzi	Czeladz
Poland	Centrum Zdrowia Psychicznego Biomed - Jan Latala	Kielce
Poland	Centrum Medyczne Plejady	Kraków
Poland	Centrum Opieki Zdrowotnej Orkan-Med	Ksawerow
Poland	Centrum Medyczne im. Dr Karola Jonschera w Lodzi	Lodz
Poland	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin
Poland	CRC Sp. Zo.o.	Poznan
Poland	Euromedis Sp. Zo.o	Szczecin
United States	Albuquerque Neuroscience	Albuquerque	New Mexico
United States	TOPAZ Clinical Research	Apopka	Florida
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Cognitive Clinical Trials	Bellevue	Nebraska
United States	Parkinson's Disease & Movement Disorders Center of Boca Raton	Boca Raton	Florida
United States	Bradenton Research Center	Bradenton	Florida
United States	ANI Neurology, PLLC Alzheimer's Memory Center	Charlotte	North Carolina
United States	Palmetto Health	Columbia	South Carolina
United States	Columbus Research & Wellness Institute	Columbus	Georgia
United States	The Ohio State University	Columbus	Ohio
United States	Mile High Research Center	Denver	Colorado
United States	Samuel and Alexia Bratton Memory Clinic	Easton	Maryland
United States	Memory Enhancement Center of America	Eatontown	New Jersey
United States	Coastal Health Care	Freeport	Maine
United States	Cognitive Clinical Trials	Gilbert	Arizona
United States	Adirondack Medical Research Center	Glens Falls	New York
United States	Finlay Medical Research Group	Greenacres City	Florida
United States	Galiz Clinical Research	Hialeah	Florida
United States	Alliance Research Center	Laguna Hills	California
United States	AdvancedMed Research	Lawrenceville	New Jersey
United States	Renew Behavioral Health	Long Beach	California
United States	Neurology Associates of Arlington, P.A.	Mansfield	Texas
United States	CNS Healthcare	Memphis	Tennessee
United States	ActivMed Practices & Research, Inc.	Methuen	Massachusetts
United States	Finlay Medical Research Group	Miami	Florida
United States	IMIC, Inc.	Miami	Florida
United States	Next Phase Research Alliance	Miami	Florida
United States	Next Phase Research Alliance - Cano Health	Miami	Florida
United States	Next Phase Research Alliance - MetroMed	Miami	Florida
United States	Premier Clinical Research Institute	Miami	Florida
United States	The Neurology Research Group	Miami	Florida
United States	Panax	Miami Lakes	Florida
United States	The NeuroCognitive Institute	Mount Arlington	New Jersey
United States	Manhattan Behavioral Medicine	New York	New York
United States	Medical Research Network	New York	New York
United States	Nathan S. Kline Institute for Psychiatric Research	New York	New York
United States	Pearl Clinical Research	Norristown	Pennsylvania
United States	Excell Research, Inc.	Oceanside	California
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Cognitive Clinical Trials	Omaha	Nebraska
United States	University of California Irvine School of Medicine	Orange	California
United States	CNS Healthcare	Orlando	Florida
United States	Asclepes Research Center	Panorama City	California
United States	Bronson Neurobehavioral Health	Paw Paw	Michigan
United States	Pines Care Research Center	Pembroke Pines	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Xenoscience	Phoenix	Arizona
United States	Neurostudies, Inc.	Port Charlotte	Florida
United States	Progressive Medical Research	Port Orange	Florida
United States	ActivMed Practices & Research Inc.	Portsmouth	New Hampshire
United States	The Alzheimer's Disease Center	Quincy	Massachusetts
United States	Raleigh Neurological Associates	Raleigh	North Carolina
United States	Artemis Clinical Research	Riverside	California
United States	CITrials	Riverside	California
United States	Metrolina Neurological Associates, PA	Rock Hill	South Carolina
United States	Northern California Research	Sacramento	California
United States	Wasatch Clinical Research, LLC	Salt Lake City	Utah
United States	Syrentys Clinical Research	Santa Ana	California
United States	Behavioral Health Care Associates	Schaumburg	Illinois
United States	Cognitive Clinical Trials	Scottsdale	Arizona
United States	Insight Clincial Trials	Shaker Heights	Ohio
United States	Kingfisher Cooperative	Spokane	Washington
United States	Axiom Clinical Research	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	Territory Neurology & Research Institute	Tucson	Arizona
United States	Tulsa Clinical Research, Inc.	Tulsa	Oklahoma
United States	Winifred Masterson Burke Medical Research Institute	White Plains	New York
United States	Grayline Clinical Drug Trials	Wichita Falls	Texas
United States	PMG Winston-Salem	Winston-Salem	North Carolina

Sponsors (4)

Lead Sponsor	Collaborator
AZTherapies, Inc.	APCER Life Sciences, KCAS Bio, PharmaConsulting Group

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Czechia,  Hungary,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External Links

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