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

Sponsor

AZTherapies, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02547818

Collaborator

PharmaConsulting Group (Other), KCAS Bio (Other), APCER Life Sciences (Other)

620

Enrollment

121

Locations

Arms

62.1

Actual Duration (Months)

5.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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

Study Type:

Interventional

Actual Enrollment :

620 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

Actual Study Start Date :

Sep 15, 2015

Actual Primary Completion Date :

Nov 13, 2020

Actual Study Completion Date :

Nov 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Group I ALZT-OP1a active capsules for inhalation and ALZT-OP1b placebo capsules for oral administration.	Drug: ALZT-OP1a 1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory Other Names: 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 1) Mast cell stabilizer, 2) Neuroinflammatory microglial modulator, 3) A-beta oligomerization inhibitor, and 4) anti-inflammatory Other Names: Cromolyn Drug: ALZT-OP1b Anti-inflammatory Other Names: 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 Names: 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

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 79 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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.

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

Locations

	Site	City	State	Country	Postal Code
1	Cognitive Clinical Trials	Gilbert	Arizona	United States	85296
2	Xenoscience	Phoenix	Arizona	United States	85004
3	Cognitive Clinical Trials	Scottsdale	Arizona	United States	85251
4	Territory Neurology & Research Institute	Tucson	Arizona	United States	85704
5	Alliance Research Center	Laguna Hills	California	United States	92653
6	Renew Behavioral Health	Long Beach	California	United States	90807
7	Excell Research, Inc.	Oceanside	California	United States	92056
8	University of California Irvine School of Medicine	Orange	California	United States	92868
9	Asclepes Research Center	Panorama City	California	United States	91402
10	Artemis Clinical Research	Riverside	California	United States	92503
11	CITrials	Riverside	California	United States	92506
12	Northern California Research	Sacramento	California	United States	95821
13	Syrentys Clinical Research	Santa Ana	California	United States	92705
14	Mile High Research Center	Denver	Colorado	United States	80218
15	TOPAZ Clinical Research	Apopka	Florida	United States	32703
16	Parkinson's Disease & Movement Disorders Center of Boca Raton	Boca Raton	Florida	United States	33486
17	Bradenton Research Center	Bradenton	Florida	United States	34205
18	Finlay Medical Research Group	Greenacres City	Florida	United States	33467
19	Galiz Clinical Research	Hialeah	Florida	United States	33016
20	Panax	Miami Lakes	Florida	United States	33014
21	The Neurology Research Group	Miami	Florida	United States	22176
22	Premier Clinical Research Institute	Miami	Florida	United States	33122
23	Finlay Medical Research Group	Miami	Florida	United States	33126
24	Next Phase Research Alliance - Cano Health	Miami	Florida	United States	33144
25	IMIC, Inc.	Miami	Florida	United States	33157
26	Next Phase Research Alliance - MetroMed	Miami	Florida	United States	33186
27	Next Phase Research Alliance	Miami	Florida	United States	33186
28	CNS Healthcare	Orlando	Florida	United States	32801
29	Pines Care Research Center	Pembroke Pines	Florida	United States	33026
30	Neurostudies, Inc.	Port Charlotte	Florida	United States	33952
31	Progressive Medical Research	Port Orange	Florida	United States	32127
32	Axiom Clinical Research	Tampa	Florida	United States	33609
33	Stedman Clinical Trials	Tampa	Florida	United States	33613
34	Columbus Research & Wellness Institute	Columbus	Georgia	United States	31904
35	Behavioral Health Care Associates	Schaumburg	Illinois	United States	60193
36	Eastern Maine Medical Center	Bangor	Maine	United States	04401
37	Coastal Health Care	Freeport	Maine	United States	04032
38	Samuel and Alexia Bratton Memory Clinic	Easton	Maryland	United States	21601
39	ActivMed Practices & Research, Inc.	Methuen	Massachusetts	United States	01844
40	The Alzheimer's Disease Center	Quincy	Massachusetts	United States	02169
41	Bronson Neurobehavioral Health	Paw Paw	Michigan	United States	49079
42	Cognitive Clinical Trials	Bellevue	Nebraska	United States	68005
43	Cognitive Clinical Trials	Omaha	Nebraska	United States	68007
44	ActivMed Practices & Research Inc.	Portsmouth	New Hampshire	United States	03801
45	Memory Enhancement Center of America	Eatontown	New Jersey	United States	07724
46	AdvancedMed Research	Lawrenceville	New Jersey	United States	08648
47	The NeuroCognitive Institute	Mount Arlington	New Jersey	United States	07856
48	Albuquerque Neuroscience	Albuquerque	New Mexico	United States	87109
49	Adirondack Medical Research Center	Glens Falls	New York	United States	12801
50	Manhattan Behavioral Medicine	New York	New York	United States	10023
51	Medical Research Network	New York	New York	United States	10128
52	Nathan S. Kline Institute for Psychiatric Research	New York	New York	United States	10128
53	Winifred Masterson Burke Medical Research Institute	White Plains	New York	United States	10605
54	ANI Neurology, PLLC Alzheimer's Memory Center	Charlotte	North Carolina	United States	28270
55	Raleigh Neurological Associates	Raleigh	North Carolina	United States	27607
56	PMG Winston-Salem	Winston-Salem	North Carolina	United States	27103
57	The Ohio State University	Columbus	Ohio	United States	43210
58	Insight Clincial Trials	Shaker Heights	Ohio	United States	44122
59	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
60	Tulsa Clinical Research, Inc.	Tulsa	Oklahoma	United States	74114
61	Pearl Clinical Research	Norristown	Pennsylvania	United States	19401
62	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
63	Palmetto Health	Columbia	South Carolina	United States	29044
64	Metrolina Neurological Associates, PA	Rock Hill	South Carolina	United States	29732
65	CNS Healthcare	Memphis	Tennessee	United States	38119
66	Neurology Associates of Arlington, P.A.	Mansfield	Texas	United States	76063
67	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
68	Wasatch Clinical Research, LLC	Salt Lake City	Utah	United States	84107
69	Kingfisher Cooperative	Spokane	Washington	United States	99202
70	St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
71	KaRa Institute of Neurological Diseases	Macquarie Park	New South Wales	Australia	2113
72	Pacific Private Clinic	Southport	Queensland	Australia	4215
73	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
74	Geelong Private Medical Centre	Geelong	Victoria	Australia	3220
75	Austin Health	Heidelberg	Victoria	Australia	3081
76	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
77	UMBAL "Dr. Georgi Stranski" EAD	Pleven		Bulgaria	5800
78	MHAT "Central Onco Hospital" Ltd.	Plovdiv		Bulgaria	4000
79	MBAL Ruse AD	Ruse		Bulgaria	7002
80	"First MHAT - Sofia" EAD	Sofia		Bulgaria	1154
81	University Multiprofile Hospital for Active Treatment "Aleksandrovska" EAD	Sofia		Bulgaria	1431
82	Medical Arts Health Research	Penticton	British Columbia	Canada	V2A 5L5
83	Medical Arts Health Research	West Vancouver	British Columbia	Canada	V7T 1C5
84	Okanagan Clinical Trials	Kelowna	Britsh Columbia	Canada	V1Y 1Z9
85	Montreal Neurological Research Institute	Québec	Montreal	Canada	H3A 284
86	True North Clinical Research	Halifax	Nova Scotia	Canada	B3S 1M7
87	True North Clinical Research	Kentville	Nova Scotia	Canada	B4N 4K9
88	JBN Medical	Burlington	Ontario	Canada	L7M 4Y1
89	Chatham-Kent Clinical Trials	Chatham	Ontario	Canada	N7l1C1
90	The Centre for Memory and Aging	East York	Ontario	Canada	M4G 3E8
91	Cliniuqe de la Memoire de l'Outouais	Gatineau	Quebec	Canada	J8T 8J1
92	Neurosanatio, s.r.o.	Litomyšl	Czech Republic	Czechia	570 01
93	Neurologie MU - Ondrej Koci, s.r.o.	Novy Bor	Czech Republic	Czechia	473 01
94	CT Center MaVfe, s.r.o	Olomouc	Czech Republic	Czechia	779 00
95	Vestra Clinics, s.r.o.	Rychnov Nad Kněžnou	Czech Republic	Czechia	516 01
96	NEUROHK, s.r.o.	Chocen		Czechia	565 01
97	Clinline Services s.r.o.	Hostivice		Czechia	253 01
98	Psychiatricka ambulance	Hradec Kralove		Czechia	503 41
99	Psychiatricka ambulance Supervize s.r.o.	Kutná Hora		Czechia	28401
100	Krajska nemocnice Liberec a.s.	Liberec		Czechia	460 63
101	A-shine, s.r.o.	Plzen		Czechia	312 00
102	Clintrial.s.r.o.	Praha		Czechia	100 00
103	Fakultni nemocnice v Motole Neurologicka klinika 2.LF UK a FN Motol	Praha		Czechia	150 06
104	INEP medical s.r.o.	Praha		Czechia	186 00
105	Neurologia Klinika Semmelweis Egyetem	Budapest		Hungary	H-1083
106	Orszagos Klinikai Idegtudomanyi Intezat	Budapest		Hungary	H-1145
107	Vaszary Kolos Korhaz	Esztergom		Hungary	H-2500
108	Bekes Megyei Pandy Kalman Korhaz	Gyula		Hungary	H-5700
109	Petz Aladar Megyei Oktato Korhaz	Győr		Hungary	09024
110	Cermed Pawel Hernik	Bialystok		Poland	15-270
111	Podlaskie Centrum Psychogeriatrii	Bialystok		Poland	15-756
112	Przychondnia Srodmiescie	Bydgoszcz		Poland	85-080
113	Centrum Medyczne KERMED	Bydgoszcz		Poland	85-231
114	Szpital Powiatowy w Czeladzi	Czeladz		Poland	41-250
115	Centrum Zdrowia Psychicznego Biomed - Jan Latala	Kielce		Poland	25-411
116	Centrum Medyczne Plejady	Kraków		Poland	30-363
117	Centrum Opieki Zdrowotnej Orkan-Med	Ksawerow		Poland	95-054
118	Centrum Medyczne im. Dr Karola Jonschera w Lodzi	Lodz		Poland	93-113
119	Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie	Lublin		Poland	20-954
120	CRC Sp. Zo.o.	Poznan		Poland	60-856
121	Euromedis Sp. Zo.o	Szczecin		Poland	70-111