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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03507790




Registration number
NCT03507790
Ethics application status
Date submitted
10/04/2018
Date registered
25/04/2018
Date last updated
1/04/2019

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.
Scientific title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.
Secondary ID [1] 0 0
COG0201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mild to Moderate 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 - CT1812
Treatment: Drugs - Placebo

Active Comparator: Active Treatment- CT1812 100 mg - CT1812 at a dose of 100 n=8 group

Active Comparator: Active Treatment- CT1812 300 mg - CT1812 at a dose of 300mg, n=8 group

Placebo Comparator: Placebo Comparator - Placebo - Placebo, n=8 group


Treatment: Drugs: CT1812
Active Study Drug

Treatment: Drugs: Placebo
Non-active study drug

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of study participants with treatment related adverse events and serious adverse events - Adverse events will be collected starting at Day 1 through Day 210 to evaluate safety.
Timepoint [1] 0 0
210 Days

Eligibility
Key inclusion criteria
1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a
diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA
criteria and at least a 6 month decline in cognitive function documented in the
medical record.

i) Non-childbearing potential for women is defined as postmenopausal (last natural
menses greater than 24 months) or undergone a documented bilateral tubal ligation or
hysterectomy. If last natural menses less than 24 months, a serum FSH value confirming
post-menopausal status can be employed.

ii) Male participants who are sexually active with a woman of child-bearing potential
must agree to use condoms during the trial and for 3 months after last dose unless the
woman is using an acceptable means of birth control. Acceptable forms of birth control
include abstinence, birth control pills, or any double combination of: intrauterine
device (IUD), male or female condom, diaphragm, sponge, and cervical cap.

2. Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid
PET ligand. Previous amyloid imaging study with a positive result will be accepted. If
none is available, then amyloid PET will be conducted during screening. Diagnostic
confirmation by a CSF sample collected at the screening visit lumbar puncture in place
of amyloid PET will also be acceptable

3. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of
Alzheimer's disease and without findings of significant exclusionary abnormalities
(see exclusion criteria, number 4). An historical MRI, up to 1 year prior to
screening, may be used as long as there is no history of intervening neurologic
disease or clinical events (such as a stroke, head trauma etc.) and the subject is
without clinical symptoms or signs suggestive of such intervening events.).

4. MMSE 18-26 inclusive.

5. No active depression and a GDS =6 (see exclusion criteria number 6).

6. Modified Hachinski = 4.

7. Formal education of eight or more years.

8. Subjects must have a caregiver/ study partner who in the opinion of the site principal
investigator, has contact with the study subject for a sufficient number of hours per
week to provide informative responses on the protocol assessments, oversee the
administration of study drug, and is willing and able to participate in all clinic
visits and some study assessments. The caregiver/ study partner must provide written
informed consent to participate in the study.

9. Subjects living at home or in the community (assisted living acceptable).

10. Ability to swallow CT1812 capsules.

11. Stable pharmacological treatment of any other chronic conditions for at least 30 days
prior to screening.

12. Subjects must be capable of providing written informed consent to the study procedures
and for use of protected health information [Health Insurance Portability and
Accountability Act (HIPAA), if applicable]. Written informed consent also shall be
obtained from the responsible caregiver. All consent processes must be undertaken in
the presence of a witness and prior to any study procedures.

13. Must consent to apolipoprotein E (ApoE) genotyping for data analysis stratification.

14. Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided,
i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for
compliance with testing procedures.

15. Must be able to complete all screening evaluations.

EXCLUSION CRITERIA:

Participants will be excluded from the study if any of the following conditions apply:

1. Hospitalization (except for planned procedures) or change of chronic concomitant
medication within one month prior to screening.

2. Subjects living in a continuous care nursing facility.

3. Contraindication to the MRI examination for any reason.

4. Screening MRI (or historical MRI, if applicable) of the brain indicative of
significant abnormality, including, but not limited to, prior hemorrhage or infarct >1
cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular
malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess
or brain tumor such as meningioma). If a small incidental meningioma is observed, the
medical monitor may be contacted to discuss eligibility..

5. Clinical or laboratory findings consistent with:

1. Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal
dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc.).

2. Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral
sclerosis, etc.).

3. Seizure disorder.

4. Other infectious, metabolic or systemic diseases affecting the central nervous
system (syphilis, present hypothyroidism, present vitamin B12 or folate
deficiency, other laboratory values etc.).

6. A current DSM-V diagnosis of active major depression, schizophrenia or bipolar
disorder. Subjects with depressive symptoms successfully managed by a stable dose of
an antidepressant are allowed entry.

7. Clinically significant, advanced or unstable disease that may interfere with outcome
evaluations, such as:

1. Chronic liver disease, liver function test abnormalities or other signs of
hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate
dehydrogenase (LDH) > 1.5 x ULN).

2. Respiratory insufficiency.

3. Renal insufficiency eGFR < 50 mL/min based on the CKD-EPI formula,
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr

4. Heart disease (myocardial infarction, unstable angina, heart failure,
cardiomyopathy within six months before screening).

5. Bradycardia (<50/min.) or tachycardia (>100/min.).

6. Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or
hypotension (systolic <90 mm Hg and/or diastolic <60 mm Hg).

7. Uncontrolled diabetes defined by HbA1c >7.5.

8. History of cancer within 3 years of screening with the exception of fully excised
non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for
at least 6 months.

9. Seropositive for human immunodeficiency virus (HIV).

10. History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive
for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).

11. Clinically significant abnormalities in screening laboratory tests, including:

a. Hematocrit less than 35% for males and less than 32% for females, absolute
neutrophil cell count of 1500/uL (with the exception of a documented history of a
chronic benign neutropenia), or platelet cell count of < 120,000/uL; INR >1.4 or other
coagulopathy, confirmed by repeat assessment of: i. Hematocrit ii. Neutrophil count
iii. Platelet count

12. Disability that may prevent the subject from completing all study requirements (e.g.
blindness, deafness, severe language difficulty, etc.).

13. Within 4 weeks of screening visit or during the course of the study, concurrent
treatment with antipsychotic agents, antiepileptics, centrally active
anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc.),
sedatives, opioids, mood stabilizers (e.g., valproate, lithium); or benzodiazepines,
with the following exception:

a. Low dose lorazepam may be used for sedation prior to MRI scan for those subjects
requiring sedation. At the discretion of the investigator, 0.5 to 1 mg may be given
orally prior to scan with a single repeat dose given if the first dose is ineffective.
No more than a total of 2 mg lorazepam may be used for the MRI scan.

14. Any disorder that could interfere with the absorption, distribution, metabolism or
excretion of drugs (e.g. small bowel disease, Crohn's disease, celiac disease, or
liver disease).

15. Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine.

16. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol
(approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV
significantly above normal value at screening.

17. Suspected or known allergy to any components of the study treatments.

18. Enrollment in another investigational study or intake of investigational drug within
the previous 30 days or five half lives of the investigational drug, whichever is
longer.

19. Intake of drugs or substances potentially involved in clinically significant induction
or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks
or five half-lives of the interacting drug prior to administration of CT1812 and
throughout the course of the study. Grapefruit juice should be avoided in the two
weeks prior to dosing and throughout the course of the study. See Appendix A for a
complete list of prohibited substances.

20. Exposure to immunomodulators, anti Aß vaccines, passive immunotherapies for AD (e.g.
monoclonal antibodies) within the past 180 days and/or exposure to BACE inhibitors
within the past 30 days.

21. Anticipated use of nonsteroidal anti-inflammatory drugs (NSAIDs) on more than 14 days
during the period from Baseline to Day 182.

22. Contraindication to undergoing an LP including, but not limited to: inability to
tolerate an appropriately flexed position for the time necessary to perform an LP;
international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of <
120,000/µL; infection at the desired lumbar puncture site; taking anti-coagulant
medication within 90 days of screening (Note: low dose aspirin is permitted);
degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus
or intracranial mass; prior history of spinal mass or trauma.

23. Any condition, which in the opinion of the investigator or the sponsor makes the
subject unsuitable for inclusion.
Minimum age
50 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Austin Health - Ivanhoe
Recruitment hospital [2] 0 0
St Vincent's Hospital Sydney - Ivanhoe
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment hospital [4] 0 0
Melbourne Health - Parkville
Recruitment hospital [5] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment postcode(s) [1] 0 0
3079 - Ivanhoe
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
3050 - Parkville
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Cognition Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week
multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's
Disease (AD).
Trial website
https://clinicaltrials.gov/show/NCT03507790
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Alyssa Galley
Address 0 0
Cognition Therapuetics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alyssa Galley
Address 0 0
Country 0 0
Phone 0 0
1 617.459.9134
Fax 0 0
Email 0 0
agalley@CogRx.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03507790