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Study of COR388 HCl in Subjects With Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03823404
Recruitment Status : Not yet recruiting
First Posted : January 30, 2019
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Cortexyme Inc.

Brief Summary:
This is a randomized, double-blind, placebo-controlled study that will assess the efficacy, safety, and tolerability of 2 dose levels of COR388 HCl in subjects with a clinical diagnosis of mild to moderate AD dementia.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: COR388 HCl capsule Drug: Placebo capsule Phase 2 Phase 3

Detailed Description:
This is a randomized, double-blind, placebo-controlled study that will assess the efficacy, safety, and tolerability of 2 dose levels of COR388 HCl oral capsules in subjects with probable AD dementia according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. The study will enroll approximately 573 generally healthy male and female subjects ≥55 and ≤80 years of age. Enrolled subjects must have a documented diagnosis of mild to moderate AD dementia. The subject should not have other conditions or brain imaging abnormalities that can explain the symptoms of dementia. All subjects will be encouraged to have LPs (during screening, week 24 and week 48) in the absence of medical conditions that can increase the risk of the procedure in the opinion of the Investigator. Cerebrospinal fluid (CSF), saliva, and blood will be analyzed for measurements of biomarkers of AD and neuroinflammation, and for the presence of bacterial deoxyribonucleic acid (DNA) of Porphyromonas gingivalis (P. gingivalis [Pg]). A subset of sites will monitor subjects for clinical evidence of periodontitis at baseline, 24 and 48 weeks.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 573 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 HCl in Subjects With Alzheimer's Disease
Estimated Study Start Date : April 1, 2019
Estimated Primary Completion Date : December 1, 2021
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: COR388 HCl 80 mg bid Drug: COR388 HCl capsule
bid

Experimental: COR388 HCl 40 mg bid Drug: COR388 HCl capsule
bid

Placebo Comparator: Placebo bid Drug: Placebo capsule
bid




Primary Outcome Measures :
  1. Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) [ Time Frame: Baseline to Week 48 ]
    Mean change in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) from baseline to the end of treatment period. ADAS-Cog 11 measures cognitive functions and non-cognitive functions such as mood and behavior. Total scores range from 0-70, with higher scores (≥ 18) indicating greater cognitive impairment. ADAS-Cog 11 score increases by 2-4 points per year on average in subjects with mild to moderate Alzheimer's Disease. A treatment period of 48 weeks was selected to allow sufficient time to demonstrate at least 2.5 points difference between active treatment and placebo on ADAS-Cog 11 at the end of the treatment period.


Secondary Outcome Measures :
  1. ADCS-ADL [ Time Frame: Baseline to Week 48 ]
    Change in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL).

  2. CDR-SB [ Time Frame: Baseline to Week 48 ]
    Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).


Other Outcome Measures:
  1. Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 48 ]
    Change in MMSE.

  2. Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline to Week 48 ]
    Change in NPI.

  3. Cerebrospinal fluid (CSF) Porphyromonas gingivalis DNA fragments [ Time Frame: Baseline to Week 48 ]
    Change in CSF Porphyromonas gingivalis DNA fragments.

  4. Winterlight Speech Assessment [ Time Frame: Baseline to Week 48 ]
    Change in Winterlight Speech Assessment.

  5. Magnetic resonance imaging [ Time Frame: Baseline to Week 48 ]
    Change in magnetic resonance imaging.

  6. Periodontal (or gum) pocket depth [ Time Frame: Baseline to Week 48 ]
    Change in periodontal (or gum) pocket depth.



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male and female.
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Subject has probable AD dementia according to the NIA-AA criteria.
  • Subject has an MMSE score 12 and 22 inclusive at both screening and Visit 2 and a ≤2-point difference between these visits.
  • 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.
  • Subject has a Modified Hachinski score ≤4 at screening.
  • Subjects with background symptomatic therapy with acetylcholine esterase 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.
  • 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.
  • Subject has body mass index <35 kg/m2 at Screening

Key Exclusion Criteria:

  • Subject has imaging consistent with a dementia diagnosis other than AD.
  • Subject has had an increase or restoration of cognition based on medical history.
  • Subject has clinical and radiological findings that fulfill the standards of the National Institute of Neurological Disorders and Stroke and Association Internationale pour la Recherché et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia.
  • 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. NOTE: Mild depression or depressive mood arising in the context of AD are not criteria for exclusion. The use of anti-depressants or the use of anti epileptic medication for non seizure-related treatment is allowed if the dose has remained stable for at least 60 days prior to enrollment.
  • Subject has any of the following laboratory findings at screening:

    1. Alanine aminotransferase >3 x upper limit of normal (ULN), aspartate aminotransferase >3 x ULN, or history of clinically significant liver disease in the Investigator's judgment.
    2. Hemoglobin ≤10 g/dl.
    3. Creatinine clearance (CL) of <45 ml/min.
    4. Poorly controlled diabetes as defined by hemoglobin A1C (HbA1C) >8.
    5. Positive blood screen for Human Immunodeficiency Virus (HIV 1 and 2), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus antibodies (HCV-Ab) at Screening.

Responsible Party: Cortexyme Inc.
ClinicalTrials.gov Identifier: NCT03823404     History of Changes
Other Study ID Numbers: COR388-010
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders