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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02547818




Registration number
NCT02547818
Ethics application status
Date submitted
10/09/2015
Date registered
11/09/2015
Date last updated
10/11/2021

Titles & IDs
Public title
Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Scientific title
A Phase III Safety and Efficacy Study of ALZT-OP1 in Subjects With Evidence of Early Alzheimer's Disease
Secondary ID [1] 0 0
AZT-001
Universal Trial Number (UTN)
Trial acronym
COGNITE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ALZT-OP1a
Treatment: Drugs - ALZT-OP1b
Other interventions - Placebo ALZT-OP1a
Other interventions - Placebo ALZT-OP1b

Active comparator: Group I - ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.

Active comparator: Group II - ALZT-OP1a active capsules for inhalation and ALZT-OP1b active tablets for oral administration.

Active comparator: Group III - ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b active tablets for oral administration.

Placebo comparator: Group IV - ALZT-OP1a placebo capsules for inhalation and ALZT-OP1b placebo tablets for oral administration.


Treatment: Drugs: ALZT-OP1a
1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory

Treatment: Drugs: ALZT-OP1b
Anti-inflammatory

Other interventions: Placebo ALZT-OP1a
Non-active capsules

Other interventions: Placebo ALZT-OP1b
Non-active tablets
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Clinical Dementia Rating-Sum of Boxes (CDR-SB)
Timepoint [1] 0 0
Baseline and Week 72
Secondary outcome [1] 0 0
Number of Treatment Emergent Adverse Events (TEAE)
Timepoint [1] 0 0
72 weeks

Eligibility
Key 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.
Minimum age
55 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/11/2020
Sample size
Target
Accrual to date
Final
620
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
KaRa Institute of Neurological Diseases - Macquarie Park
Recruitment hospital [3] 0 0
Pacific Private Clinic - Southport
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [5] 0 0
Geelong Private Medical Centre - Geelong
Recruitment hospital [6] 0 0
Austin Health - Heidelberg
Recruitment hospital [7] 0 0
Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2113 - Macquarie Park
Recruitment postcode(s) [3] 0 0
4215 - Southport
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3220 - Geelong
Recruitment postcode(s) [6] 0 0
3081 - Heidelberg
Recruitment postcode(s) [7] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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California
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Colorado
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Florida
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Georgia
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Illinois
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Maine
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Maryland
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Massachusetts
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Michigan
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Nebraska
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New Hampshire
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New Jersey
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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Texas
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Pleven
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Britsh Columbia
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Nova Scotia
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Chocen
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Hostivice
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Hradec Kralove
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Kutná Hora
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Liberec
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Plzen
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Praha
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Hungary
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Budapest
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Hungary
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Esztergom
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Hungary
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Gyula
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Gyor
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Bialystok
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Bydgoszcz
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Czeladz
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Kielce
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Kraków
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Ksawerow
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Lodz
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Lublin
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Poznan
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Szczecin

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AZTherapies, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
PharmaConsulting Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
KCAS Bio
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
APCER Life Sciences
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT02547818
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David R. Elmaleh, PhD
Address 0 0
AZTherapies, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02547818