Study of COR388 in Subjects with Alzheimer’s Disease
- Conditions
- Alzheimer’s DiseaseMedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852Therapeutic area: Psychiatry and Psychology [F] - Psychological processes [F02]
- Registration Number
- EUCTR2019-000370-27-NL
- Lead Sponsor
- Cortexyme, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 573
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., intrauterine device plus condom or true abstinence
defined as in line with the preferred and usual lifestyle of
the subject. Per
1. Subject has imaging consistent with other differential dementia diagnoses other than the diagnosis of AD.
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 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.
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, 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 or ventricular ectopy on the screening ECG or Brugada pattern on the ECG.
8. Subject with major stroke, uncontrolled seizure disorder, or other medical illnesses that in the Investigator’s opinion will increase the subject’s risk of participation in the study or confound study assessments.
9. Subject with history or current evidence of major neurological or psychiatric illness such as schizophrenia, bipolar disorder, Parkinson’s Disease, etc. Subjects with major depressive disorder that may interfere with the patient’s ability to perform the study and all assessments.
10. Subject with history of violent or aggressive behavior that requires medication to control.
11. Subjects with active suicidal thoughts (Type 4 or 5 on the C-SSRS) in the 6 months preceding screening or at baseline; or have a history of a suicide attempt in the previous 2 years, or more than 1 lifetime suicide attempt; or are at serious suicide risk in the Investigator’s clinical judgment.
12. Subject with history of alcohol or drug use disorder within 12 months of screening .
13. Subject with previous treatment with investigational vaccine therapy for AD.
14. Subject has participated in another Investigational New Drug (IND) research study involving small molecule drugs within 60 days or biological drugs within 90 days prior to the first dose of study drug or 5 half-lives of the investigational drug, whichever is longer.
15. Subject has a history of epilepsy or seizure disorder requiring ongoing treatment, or any seizure or loss of consciousness within
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Assess the efficacy of 2 dose levels of COR388 HCl in Alzheimer’s disease (AD) subjects;<br>Assess the safety and tolerability of 2 dose levels of COR388 HCl in AD subjects;Secondary Objective: Not applicable;Primary end point(s): The two co-primary endpoints are:<br>Mean change in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) from baseline to the end of treatment period.<br>Mean change in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) from baseline to the end of treatment period;Timepoint(s) of evaluation of this end point: 48 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).<br>•Change in Mini-Mental State Examination (MMSE)<br>•Change in Neuropsychiatric Inventory (NPI);Timepoint(s) of evaluation of this end point: 48 weeks