Clinical trial NCT02547818: Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Official title: A Phase III Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Early stage AD
MCI
aMCI
prodromal
Memory loss
Memory problems
Aging
Early Alzheimer's Disease
Early AD
Lead sponsor: AZTherapies, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PharmaConsulting Group
name: KCAS Bio
name: APCER Life Sciences
First posted: 2015-09-11
Enrollment: 620
Sex: ALL
Minimum age (years): 55
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Clinical Dementia Rating-Sum of Boxes (CDR-SB)
timeFrame: Baseline and Week 72
Secondary outcomes:
measure: Number of Treatment Emergent Adverse Events (TEAE)
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Cognitive Clinical Trials
state: Arizona
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Scottsdale
country: United States
facility: Cognitive Clinical Trials
state: Arizona
city: Tucson
country: United States
facility: Territory Neurology & Research Institute
state: Arizona
city: Laguna Hills
country: United States
facility: Alliance Research Center
state: California
city: Long Beach
country: United States
facility: Renew Behavioral Health
state: California
city: Oceanside
country: United States
facility: Excell Research, Inc.
state: California
city: Orange
country: United States
facility: University of California Irvine School of Medicine
state: California
city: Panorama City
country: United States
facility: Asclepes Research Center
state: California
city: Riverside
country: United States
facility: Artemis Clinical Research
state: California
city: Riverside
country: United States
facility: CITrials
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: Santa Ana
country: United States
facility: Syrentys Clinical Research
state: California
city: Denver
country: United States
facility: Mile High Research Center
state: Colorado
city: Apopka
country: United States
facility: TOPAZ Clinical Research
state: Florida
city: Boca Raton
country: United States
facility: Parkinson's Disease & Movement Disorders Center of Boca Raton
state: Florida
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Greenacres City
country: United States
facility: Finlay Medical Research Group
state: Florida
city: Hialeah
country: United States
facility: Galiz Clinical Research
state: Florida
city: Miami Lakes
country: United States
facility: Panax
state: Florida
city: Miami
country: United States
facility: The Neurology Research Group
state: Florida
city: Miami
country: United States
facility: Premier Clinical Research Institute
state: Florida
city: Miami
country: United States
facility: Finlay Medical Research Group
state: Florida
city: Miami
country: United States
facility: Next Phase Research Alliance - Cano Health
state: Florida
city: Miami
country: United States
facility: IMIC, Inc.
state: Florida
city: Miami
country: United States
facility: Next Phase Research Alliance - MetroMed
state: Florida
city: Miami
country: United States
facility: Next Phase Research Alliance
state: Florida
city: Orlando
country: United States
facility: CNS Healthcare
state: Florida
city: Pembroke Pines
country: United States
facility: Pines Care Research Center
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies, Inc.
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Columbus
country: United States
facility: Columbus Research & Wellness Institute
state: Georgia
city: Schaumburg
country: United States
facility: Behavioral Health Care Associates
state: Illinois
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Freeport
country: United States
facility: Coastal Health Care
state: Maine
city: Easton
country: United States
facility: Samuel and Alexia Bratton Memory Clinic
state: Maryland
city: Methuen
country: United States
facility: ActivMed Practices & Research, Inc.
state: Massachusetts
city: Quincy
country: United States
facility: The Alzheimer's Disease Center
state: Massachusetts
city: Paw Paw
country: United States
facility: Bronson Neurobehavioral Health
state: Michigan
city: Bellevue
country: United States
facility: Cognitive Clinical Trials
state: Nebraska
city: Omaha
country: United States
facility: Cognitive Clinical Trials
state: Nebraska
city: Portsmouth
country: United States
facility: ActivMed Practices & Research Inc.
state: New Hampshire
city: Eatontown
country: United States
facility: Memory Enhancement Center of America
state: New Jersey
city: Lawrenceville
country: United States
facility: AdvancedMed Research
state: New Jersey
city: Mount Arlington
country: United States
facility: The NeuroCognitive Institute
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience
state: New Mexico
city: Glens Falls
country: United States
facility: Adirondack Medical Research Center
state: New York
city: New York
country: United States
facility: Manhattan Behavioral Medicine
state: New York
city: New York
country: United States
facility: Medical Research Network
state: New York
city: New York
country: United States
facility: Nathan S. Kline Institute for Psychiatric Research
state: New York
city: White Plains
country: United States
facility: Winifred Masterson Burke Medical Research Institute
state: New York
city: Charlotte
country: United States
facility: ANI Neurology, PLLC Alzheimer's Memory Center
state: North Carolina
city: Raleigh
country: United States
facility: Raleigh Neurological Associates
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Winston-Salem
state: North Carolina
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Shaker Heights
country: United States
facility: Insight Clincial Trials
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Tulsa
country: United States
facility: Tulsa Clinical Research, Inc.
state: Oklahoma
city: Norristown
country: United States
facility: Pearl Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Columbia
country: United States
facility: Palmetto Health
state: South Carolina
city: Rock Hill
country: United States
facility: Metrolina Neurological Associates, PA
state: South Carolina
city: Memphis
country: United States
facility: CNS Healthcare
state: Tennessee
city: Mansfield
country: United States
facility: Neurology Associates of Arlington, P.A.
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Salt Lake City
country: United States
facility: Wasatch Clinical Research, LLC
state: Utah
city: Spokane
country: United States
facility: Kingfisher Cooperative
state: Washington
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Macquarie Park
country: Australia
facility: KaRa Institute of Neurological Diseases
state: New South Wales
city: Southport
country: Australia
facility: Pacific Private Clinic
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Geelong
country: Australia
facility: Geelong Private Medical Centre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Pleven
country: Bulgaria
facility: UMBAL "Dr. Georgi Stranski" EAD
city: Plovdiv
country: Bulgaria
facility: MHAT "Central Onco Hospital" Ltd.
city: Ruse
country: Bulgaria
facility: MBAL Ruse AD
city: Sofia
country: Bulgaria
facility: "First MHAT - Sofia" EAD
city: Sofia
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD
city: Penticton
country: Canada
facility: Medical Arts Health Research
state: British Columbia
city: West Vancouver
country: Canada
facility: Medical Arts Health Research
state: British Columbia
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: Britsh Columbia
city: Québec
country: Canada
facility: Montreal Neurological Research Institute
state: Montreal
city: Halifax
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: Kentville
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: Burlington
country: Canada
facility: JBN Medical
state: Ontario
city: Chatham
country: Canada
facility: Chatham-Kent Clinical Trials
state: Ontario
city: East York
country: Canada
facility: The Centre for Memory and Aging
state: Ontario
city: Gatineau
country: Canada
facility: Cliniuqe de la Memoire de l'Outouais
state: Quebec
city: Litomyšl
country: Czechia
facility: Neurosanatio, s.r.o.
state: Czech Republic
city: Novy Bor
country: Czechia
facility: Neurologie MU - Ondrej Koci, s.r.o.
state: Czech Republic
city: Olomouc
country: Czechia
facility: CT Center MaVfe, s.r.o
state: Czech Republic
city: Rychnov Nad Kněžnou
country: Czechia
facility: Vestra Clinics, s.r.o.
state: Czech Republic
city: Chocen
country: Czechia
facility: NEUROHK, s.r.o.
city: Hostivice
country: Czechia
facility: Clinline Services s.r.o.
city: Hradec Kralove
country: Czechia
facility: Psychiatricka ambulance
city: Kutná Hora
country: Czechia
facility: Psychiatricka ambulance Supervize s.r.o.
city: Liberec
country: Czechia
facility: Krajska nemocnice Liberec a.s.
city: Plzen
country: Czechia
facility: A-shine, s.r.o.
city: Praha
country: Czechia
facility: Clintrial.s.r.o.
city: Praha
country: Czechia
facility: Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol
city: Praha
country: Czechia
facility: INEP medical s.r.o.
city: Budapest
country: Hungary
facility: Neurologia Klinika Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Orszagos Klinikai Idegtudomanyi Intezat
city: Esztergom
country: Hungary
facility: Vaszary Kolos Korhaz
city: Gyula
country: Hungary
facility: Bekes Megyei Pandy Kalman Korhaz
city: Győr
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz
city: Bialystok
country: Poland
facility: Cermed Pawel Hernik
city: Bialystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: Przychondnia Srodmiescie
city: Bydgoszcz
country: Poland
facility: Centrum Medyczne KERMED
city: Czeladz
country: Poland
facility: Szpital Powiatowy w Czeladzi
city: Kielce
country: Poland
facility: Centrum Zdrowia Psychicznego Biomed - Jan Latala
city: Kraków
country: Poland
facility: Centrum Medyczne Plejady
city: Ksawerow
country: Poland
facility: Centrum Opieki Zdrowotnej Orkan-Med
city: Lodz
country: Poland
facility: Centrum Medyczne im. Dr Karola Jonschera w Lodzi
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
city: Poznan
country: Poland
facility: CRC Sp. Zo.o.
city: Szczecin
country: Poland
facility: Euromedis Sp. Zo.o
Study officials:
affiliation: AZTherapies, Inc.
name: David R. Elmaleh, PhD
role: STUDY_DIRECTOR
References: