A Randomized, Double-Blind, Placebo Controlled Study of COR388 HCl in Subjects with Alzheimer*s Disease
- Conditions
- Alzheimer's diseasedementianeurodegenerative disease10012272
- Registration Number
- NL-OMON54863
- Lead Sponsor
- Cortexyme, Inc.
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 31
1. Subject has provided full written informed consent prior to the performance
of any protocol-specified procedure; or if unable to provide informed consent
due to cognitive status, subject has provided assent and a legally authorized
representative has provided full written informed consent on behalf of the
subject.
2. Caregiver has provided full written informed consent, on a separate informed
consent form (ICF), on his/her own behalf prior to the performance of any
protocol-specified procedure.
3. Male and female subjects must be 55 years to 80 years of age, at the time of
consent.
4. Subject has probable AD dementia according to the NIA-AA criteria (McKhann
2011) with clinical evidence of progressive cognitive decline in the last year.
Clinical decline will be determined based on serial cognitive test scores, if
available, or subject/caregiver report as documented by the Investigator.
5. Subject has an MMSE score between 12 and 24 inclusive at both screening and
Visit 2 and a <=3-point difference between these visits.
6. Subject has a Modified Hachinski score <=4 at screening.
7. Subject has brain MRI scan consistent with the diagnosis of AD performed
during the screening period. Computed Tomography scan can be used only if the
subject has an absolute contraindication for MRI.
8. Subject has a primary caregiver willing to accept responsibility for
supervising the treatment (e.g., administering study drug), accompanying the
study subject to clinic visits and assessing the condition of the subject
throughout the study in accordance with all protocol requirements.
9. Subject is not likely to experience a change in living conditions (e.g.,
institutionalization, moving to a different city, etc.), or change in primary
caregiver, during participation in the trial.
10. Subjects with background symptomatic therapy with acetylcholinesterase
inhibitors, and/or memantine, are allowed as long as the dose has been stable
for 90 days prior to screening and no changes are planned during the study.
11. Subjects who have occasional use of sedative agents are acceptable, but
these agents should not be given within 48 hours prior to cognitive assessments.
12. Subjects who have background medications used for stable chronic illnesses
that are not prohibited by the protocol are allowed. The dose of psychoactive
drugs must be stable for 30 days prior to screening, and no changes must be
planned during the study unless for safety reasons.
13. Subject has body mass index <38 kg/m2 at Screening.
14. Subject must be able to ingest oral medications and can swallow the study
drug without breaking or crushing.
15. Subject must be willing to undergo Apolipoprotein E genotype (ApoE) genetic
testing (ApoE results may be disclosed after trial completion).
16. Subjects participating in the study must meet one of the following criteria:
a. Females: Surgically sterilized (e.g., hysterectomy, bilateral oophorectomy
or tubal ligation) for at least 6 months or postmenopausal (postmenopausal
females must have no menstrual bleeding for at least 1 year). If not
postmenopausal, agree to use a highly effective method of contraception, that
can achieve a failure rate of less than 1% per year when used consistently and
correctly, such as hormonal contraception or a double barrier method (e.g.,
intraut
Subjects will not be eligible to participate in this study if they meet any of
the following exclusion criteria:
1. Subject has imaging consistent with other differential dementia diagnoses
other than the diagnosis of AD. For example, any suggestion of vascular disease
including multiple infarction involving large blood vessels or localized single
infarction (angular gyrus, thalamus, anterior cerebral artery and posterior
cerebral artery region), multiple lacunae of the basal nuclei or white matter
or extensive lesions of the periventricular white matter or combination of
several lesions are considered exclusionary. Additionally, any single lacune
in an area known to impact cognition such as the hippocampus will also be
exclusionary. Finally, Probable CAA with/without supporting pathological
evidence according to the modified Boston criteria, if in the opinion of the
investigator this may be contributing to symptoms overlapping with those of AD
or confound neuropsychological assessments, would be exclusionary.
Importantly, should there be any evidence of neurologic symptoms between
scanning and baseline visits, rescanning is necessary to ensure proper patient
selection.
2. Subject has had an increase or restoration of cognition based on medical
history.
3. Subjects who meet the following imaging exclusion criteria will not be
included in this study:
a. Claustrophobia that will result in significant anxiety and difficulty lying
still for brain imaging (MRI or CT scan).
b. Severe motor problems or chronic pain indication that prevents the subject
from lying still for brain imaging.
4. Subject with history of cancer requiring systemic therapy in the last 5
years; except for localized cancer of the skin and in-situ cervical cancer
successfully treated with surgical excision. Stable (for at least 90 days)
prostate cancer is allowed.
5. Subject has a contraindication for LP, such as infected skin over the needle
entry site, possible increased intracranial pressure, severe thrombocytopenia
or coagulopathy, suspected spinal epidural abscess, or spinal structural
abnormalities that would interfere with LP procedures.
6. Subject has evidence of clinically significant unstable cardiovascular,
pulmonary, renal, hepatic, gastrointestinal, neurologic or metabolic disease
within 6 months prior to Screening.
7. Subject has any of the following cardiovascular conditions:
a. Unstable angina, uncompensated and/or symptomatic congestive heart failure
(Grade 2 or higher on the New York Heart Association scale) or myocardial
infarction within 6 months.
b. Acute or poorly controlled blood pressure >180 mmHg systolic or >100 mmHg
diastolic.
c. Current, or recent history of, any of the following that are clinically
significant in the investigator's judgment: arrhythmia, hypotension, heart
block (1st, 2nd or 3rd degree AV block), ANY bundle branch block, ventricular
pacing, symptomatic ectopy, unstable arrhythmias including atrial fibrillation;
stable atrial fibrillation is allowed.
d. History of prolonged QT or prolonged QT on screening ECG (QTcF *480 msec).
e. History of prolonged PR interval or prolonged PR interval on screening ECG
(PR >210 msec).
f. History of prolonged QRS interval or prolonged QRS interval on screening ECG
(QRS >120 msec).
g. Supraventricular
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The 2 primary endpoints are:<br /><br>• Mean change in Alzheimer*s Disease Assessment Scale-Cognitive Subscale 11<br /><br>(ADAS-Cog 11) from baseline to the end of treatment period.<br /><br>• Mean change in Alzheimer*s Disease Cooperative Study Group- Activities of<br /><br>Daily Living (ADCS-ADL) from baseline to the end of treatment period.</p><br>
- Secondary Outcome Measures
Name Time Method