Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
- Conditions
- Alzheimer's Disease
- Interventions
- Registration Number
- NCT02547818
- Lead Sponsor
- AZTherapies, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 620
-
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:
-
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;
-
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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Group I ALZT-OP1a ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration. Group I Placebo ALZT-OP1b ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration. Group IV Placebo ALZT-OP1a ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration. Group IV Placebo ALZT-OP1b ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration. Group II ALZT-OP1a ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration. Group II ALZT-OP1b ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration. Group III ALZT-OP1b ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration. Group III Placebo ALZT-OP1a ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration.
- Primary Outcome Measures
Name Time Method Clinical Dementia Rating-Sum of Boxes (CDR-SB) 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
Name Time Method Number of Treatment Emergent Adverse Events (TEAE) 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.
Trial Locations
- Locations (114)
Syrentys Clinical Research
🇺🇸Santa Ana, California, United States
CITrials
🇺🇸Riverside, California, United States
Parkinson's Disease & Movement Disorders Center of Boca Raton
🇺🇸Boca Raton, Florida, United States
Samuel and Alexia Bratton Memory Clinic
🇺🇸Easton, Maryland, United States
Artemis Clinical Research
🇺🇸Riverside, California, United States
Excell Research, Inc.
🇺🇸Oceanside, California, United States
CRC Sp. Zo.o.
🇵🇱Poznan, Poland
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
CNS Healthcare
🇺🇸Memphis, Tennessee, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Pines Care Research Center
🇺🇸Pembroke Pines, Florida, United States
Renew Behavioral Health
🇺🇸Long Beach, California, United States
TOPAZ Clinical Research
🇺🇸Apopka, Florida, United States
ActivMed Practices & Research, Inc.
🇺🇸Methuen, Massachusetts, United States
ActivMed Practices & Research Inc.
🇺🇸Portsmouth, New Hampshire, United States
Panax
🇺🇸Miami Lakes, Florida, United States
Neurostudies, Inc.
🇺🇸Port Charlotte, Florida, United States
Szpital Powiatowy w Czeladzi
🇵🇱Czeladz, Poland
Territory Neurology & Research Institute
🇺🇸Tucson, Arizona, United States
Tulsa Clinical Research, Inc.
🇺🇸Tulsa, Oklahoma, United States
Galiz Clinical Research
🇺🇸Hialeah, Florida, United States
Przychondnia Srodmiescie
🇵🇱Bydgoszcz, Poland
Clintrial.s.r.o.
🇨🇿Praha, Czechia
Medical Research Network
🇺🇸New York, New York, United States
INEP medical s.r.o.
🇨🇿Praha, Czechia
Bekes Megyei Pandy Kalman Korhaz
🇭🇺Gyula, Hungary
Behavioral Health Care Associates
🇺🇸Schaumburg, Illinois, United States
Kingfisher Cooperative
🇺🇸Spokane, Washington, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Cermed Pawel Hernik
🇵🇱Bialystok, Poland
Orszagos Klinikai Idegtudomanyi Intezat
🇭🇺Budapest, Hungary
A-shine, s.r.o.
🇨🇿Plzen, Czechia
Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol
🇨🇿Praha, Czechia
The Alzheimer's Disease Center
🇺🇸Quincy, Massachusetts, United States
Bronson Neurobehavioral Health
🇺🇸Paw Paw, Michigan, United States
Palmetto Health
🇺🇸Columbia, South Carolina, United States
Centrum Medyczne KERMED
🇵🇱Bydgoszcz, Poland
Centrum Medyczne Plejady
🇵🇱Kraków, Poland
Centrum Opieki Zdrowotnej Orkan-Med
🇵🇱Ksawerow, Poland
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Vaszary Kolos Korhaz
🇭🇺Esztergom, Hungary
Neurologia Klinika Semmelweis Egyetem
🇭🇺Budapest, Hungary
Pearl Clinical Research
🇺🇸Norristown, Pennsylvania, United States
Neurology Associates of Arlington, P.A.
🇺🇸Mansfield, Texas, United States
Grayline Clinical Drug Trials
🇺🇸Wichita Falls, Texas, United States
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
Euromedis Sp. Zo.o
🇵🇱Szczecin, Poland
Neurologie MU - Ondrej Koci, s.r.o.
🇨🇿Novy Bor, Czech Republic, Czechia
Neurosanatio, s.r.o.
🇨🇿Litomyšl, Czech Republic, Czechia
Medical Arts Health Research
🇨🇦West Vancouver, British Columbia, Canada
Xenoscience
🇺🇸Phoenix, Arizona, United States
The Neurology Research Group
🇺🇸Miami, Florida, United States
Premier Clinical Research Institute
🇺🇸Miami, Florida, United States
Finlay Medical Research Group
🇺🇸Miami, Florida, United States
Next Phase Research Alliance
🇺🇸Miami, Florida, United States
Next Phase Research Alliance - Cano Health
🇺🇸Miami, Florida, United States
IMIC, Inc.
🇺🇸Miami, Florida, United States
Next Phase Research Alliance - MetroMed
🇺🇸Miami, Florida, United States
Cutting Edge Research Group
🇺🇸Oklahoma City, Oklahoma, United States
Wasatch Clinical Research, LLC
🇺🇸Salt Lake City, Utah, United States
Mile High Research Center
🇺🇸Denver, Colorado, United States
Cognitive Clinical Trials
🇺🇸Omaha, Nebraska, United States
NEUROHK, s.r.o.
🇨🇿Chocen, Czechia
Psychiatricka ambulance
🇨🇿Hradec Kralove, Czechia
Krajska nemocnice Liberec a.s.
🇨🇿Liberec, Czechia
Axiom Clinical Research
🇺🇸Tampa, Florida, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
Alliance Research Center
🇺🇸Laguna Hills, California, United States
Asclepes Research Center
🇺🇸Panorama City, California, United States
University of California Irvine School of Medicine
🇺🇸Orange, California, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Coastal Health Care
🇺🇸Freeport, Maine, United States
Memory Enhancement Center of America
🇺🇸Eatontown, New Jersey, United States
AdvancedMed Research
🇺🇸Lawrenceville, New Jersey, United States
The NeuroCognitive Institute
🇺🇸Mount Arlington, New Jersey, United States
Manhattan Behavioral Medicine
🇺🇸New York, New York, United States
Nathan S. Kline Institute for Psychiatric Research
🇺🇸New York, New York, United States
Winifred Masterson Burke Medical Research Institute
🇺🇸White Plains, New York, United States
ANI Neurology, PLLC Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
The Ohio State University
🇺🇸Columbus, Ohio, United States
Raleigh Neurological Associates
🇺🇸Raleigh, North Carolina, United States
Insight Clincial Trials
🇺🇸Shaker Heights, Ohio, United States
KaRa Institute of Neurological Diseases
🇦🇺Macquarie Park, New South Wales, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
UMBAL "Dr. Georgi Stranski" EAD
🇧🇬Pleven, Bulgaria
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD
🇧🇬Sofia, Bulgaria
Okanagan Clinical Trials
🇨🇦Kelowna, Britsh Columbia, Canada
"First MHAT - Sofia" EAD
🇧🇬Sofia, Bulgaria
True North Clinical Research
🇨🇦Kentville, Nova Scotia, Canada
Montreal Neurological Research Institute
🇨🇦Québec, Montreal, Canada
JBN Medical
🇨🇦Burlington, Ontario, Canada
Chatham-Kent Clinical Trials
🇨🇦Chatham, Ontario, Canada
Cliniuqe de la Memoire de l'Outouais
🇨🇦Gatineau, Quebec, Canada
CT Center MaVfe, s.r.o
🇨🇿Olomouc, Czech Republic, Czechia
The Centre for Memory and Aging
🇨🇦East York, Ontario, Canada
Clinline Services s.r.o.
🇨🇿Hostivice, Czechia
Psychiatricka ambulance Supervize s.r.o.
🇨🇿Kutná Hora, Czechia
Adirondack Medical Research Center
🇺🇸Glens Falls, New York, United States
Columbus Research & Wellness Institute
🇺🇸Columbus, Georgia, United States
Metrolina Neurological Associates, PA
🇺🇸Rock Hill, South Carolina, United States
MHAT "Central Onco Hospital" Ltd.
🇧🇬Plovdiv, Bulgaria
MBAL Ruse AD
🇧🇬Ruse, Bulgaria
Pacific Private Clinic
🇦🇺Southport, Queensland, Australia
Vestra Clinics, s.r.o.
🇨🇿Rychnov Nad Kněžnou, Czech Republic, Czechia
Petz Aladar Megyei Oktato Korhaz
🇭🇺Győr, Hungary
Northern California Research
🇺🇸Sacramento, California, United States
PMG Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie
🇵🇱Lublin, Poland
Centrum Zdrowia Psychicznego Biomed - Jan Latala
🇵🇱Kielce, Poland
Centrum Medyczne im. Dr Karola Jonschera w Lodzi
🇵🇱Lodz, Poland
Albuquerque Neuroscience
🇺🇸Albuquerque, New Mexico, United States
Geelong Private Medical Centre
🇦🇺Geelong, Victoria, Australia
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States