Study of COR388 in Subjects with Alzheimer’s Disease
- Conditions
- Alzheimer’s DiseaseMedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852Therapeutic area: Psychiatry and Psychology [F] - Psychological processes [F02]
- Registration Number
- EUCTR2019-000370-27-ES
- Lead Sponsor
- Cortexyme, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- 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 22 inclusive at both screening and Visit 2 and a =2-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) 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 double method of contraception, one of which is a barrier method (e.g., intrauterine device plus condom, spermicidal gel plus condom) 30 days prior to dosing until 30 days after last do
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 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 basal cell carcinoma 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 evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic, gastrointestinal, neurologic or metabolic disease within 6 months prior to Screening.
6.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, bundle branch block, symptomatic ectopy, unstable arrhythmias including atrial fibrillation; stable atrial fibrillation is allowed.
d. History of prolonged QT or prolonged QT on screening ECG (QTcF > or =500 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 >110 msec).
g. Frequent supraventricular or ventricular ectopy on the screening ECG
7.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.
8.Subject with history or current evidence of major psychiatric illness such as schizophrenia, bipolar disorder, or major depressive disorder that may interfere with the patient’s ability to perform the study and all assessments.
9.Subject with history of violent or aggressive behavior that requires medication to control.
10.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.
11.Subject with history of alcohol or drug use disorder within 12 months of screening as defined by the Diagnostic and Statistical Manual of Mental Disorders-5.
12.Subject with previous treatment with investigational vaccine therapy for AD.
13.Subject has participated in another Investigational New Drug (IND) research study involving small molecule drugs within 60 day
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> 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<br> ;Secondary Objective: Not applicable;Primary end point(s): Mean change in Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) from baseline to the end of treatment period.;Timepoint(s) of evaluation of this end point: 54 weeks
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): •Change in Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL); and<br> •Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).<br> ;Timepoint(s) of evaluation of this end point: 54 weeks