Clinical Trials Register

Summary
EudraCT Number:	2015-002147-34
Sponsor's Protocol Code Number:	AZT-001
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-11-03
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2015-002147-34

A.3

Full title of the trial

A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

KLINICKÉ HODNOCENÍ FÁZE III POSUZUJÍCÍ BEZPEČNOST A ÚČINNOST ALZT-OP1 U PACIENTŮ S PROKÁZANÝM POČÁTEČNÍM STADIEM ALZHEIMEROVY NEMOCI

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

A.4.1

Sponsor's protocol code number

AZT-001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AZTherapies, Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AZTherapies, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AZTherapies, Inc.
B.5.2	Functional name of contact point	David Brazier
B.5.3	Address:
B.5.3.1	Street Address	222 Berkeley Street., 12th Floor,
B.5.3.2	Town/ city	Boston
B.5.3.3	Post code	MA 02199
B.5.3.4	Country	United States
B.5.4	Telephone number	+1857453 66 73
B.5.5	Fax number	+1617482 33 37
B.5.6	E-mail	david.brazier@aztherapies.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Cromolyn
D.3.2	Product code	ALZT-OP1a
D.3.4	Pharmaceutical form	Inhalation powder, hard capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SODIUM CROMOGLICATE
D.3.9.1	CAS number	15826-37-6
D.3.9.2	Current sponsor code	ALZT-OP1a
D.3.9.3	Other descriptive name	SODIUM CROMOGLICATE
D.3.9.4	EV Substance Code	SUB12286MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	17.1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Ibuprofen
D.3.2	Product code	ALZT-OP1b
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IBUPROFEN
D.3.9.2	Current sponsor code	ALZT-OP1b
D.3.9.3	Other descriptive name	IBUPROFEN
D.3.9.4	EV Substance Code	SUB08098MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Inhalation powder, hard capsule
D.8.4	Route of administration of the placebo	Inhalation use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Early stage of Alzheimer's Disease.

E.1.1.1

Medical condition in easily understood language

Disease with mild cognitive and functional impairment affected memory, thinking and orientation.

E.1.1.2

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10001896
E.1.2	Term	Alzheimer's disease
E.1.2	System Organ Class	100000004852

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the safety and tolerability of a combination treatment regimen (ALZT OP1)of oral inhaled cromolyn, plus oral ibuprofen tablets, compared to each of the single component groups.
To determine whether this combination treatment regimen slows down, arrests or reverses cognitive and functional decline in subjects with evidence of early AD.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 55-79 years old (inclusive);
2. ≥ 8 years of education (any type of schooling);
3. 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;
4. Evidence of early AD, as defined by all of the following:
a. Memory complaint by subject or study partner that is verified by a study partner;
b. 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):
i. ≤ 8 for 16 or more years of education, or
ii. ≤ 4 for 8-15 years of education;
c. Essentially preserved general cognitive function;
d. Largely intact functional activities;
e. Not demented;
5. CSF biomarker results consistent with early AD, including CSF Aβ-42 levels ≥ 180 pg/mL and ≤ 690 pg/mL;
6. Clinical Dementia Rating (Global) = 0.5; Memory Box Score must be at least 0.5;
7. Must be fluent in the language of the cognitive testing material being administered;
8. Stability of permitted medications for 4 weeks prior to study entry; 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 duration of study;
9. Visual and auditory acuity adequate for neuropsychological testing;
10. Good general health with no diseases expected to interfere with the study;
11. Must provide written informed consent for APOe4 genotype testing;
12. Must provide written informed consent for CSF sampling.

E.4

Principal exclusion criteria

1. 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;
2. Major depressive episode, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) within the past 1 year, which could lead to difficulty complying with the protocol);
3. History of schizophrenia or bipolar disorder (DSM-IV criteria);
4. History of alcohol or substance abuse or dependence within the past 3 years (DSM-IVcriteria);
5. 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 stable dose for at least 12 weeks prior to study entry;
6. Investigational agents are prohibited one month prior to entry and for the duration of the trial;
7. Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
8. Currently taking cromolyn, or have taken cromolyn, within the past 12 months;
9. Chronic daily use of high-dose NSAID for osteoarthritis, rheumatoid arthritis, or other chronic inflammatory diseases (“chronic” defined as 3200 mg/day for > two weeks);
10. Chronic daily use of aspirin exceeding standard of care guidelines for low dose aspirin therapy for prevention of stroke and/or other recommended uses;
11. Allergy to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®,etc.);
12. Allergies to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;
13. Clinically significant respiratory disorders with impaired respiratory effort or difficulty taking inhaled drugs; (examples: Stage III-IV COPD, emphysema);
14. Uncontrolled chronic asthma;
15. 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;
16. Taking inhaled protein products on a chronic basis (such as insulin, PTH, etc.)
17. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol;
18. Pregnancy or lactation for female subjects of child-bearing potential (i.e., < two years post-menopausal or not surgically sterile)
19. For sexually active male subjects, unwillingness or incapability of using appropriate contraception methods;
20. Severe renal or hepatic impairment.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is the difference in performance in the
ALZT-OP1 combination treatment group compared to each of
the single component groups, as quantified by the mean
change from baseline to week 72 in points scored on the
Clinical Dementia Rating-Sum of Boxes (CDR-SB).
The primary efficacy variable is change in CDR-SB from
baseline during the study.

E.5.1.1

Timepoint(s) of evaluation of this end point

72 weeks

E.5.2

Secondary end point(s)

not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

not applicable

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Bulgaria

Czech Republic

Hungary

Poland

Romania

United States

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLP

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

400

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

175

F.4.2

For a multinational trial

F.4.2.1

In the EEA

250

F.4.2.2

In the whole clinical trial

600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-04-04

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-02-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-11-13

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