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Trial record 1 of 2 for:    Cortexyme | Alzheimer Disease
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GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03823404
Recruitment Status : Active, not recruiting
First Posted : January 30, 2019
Last Update Posted : October 23, 2020
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 in subjects with a clinical diagnosis of mild to moderate AD dementia.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: COR388 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 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.

The study will consist of 3 periods: a screening period of up to 6 weeks, a treatment period of up to 48 weeks, and a safety follow-up period of 6 weeks.

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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: GAIN Trial: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 in Subjects With Alzheimer's Disease
Actual Study Start Date : March 28, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

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

Experimental: COR388 40 mg bid Drug: COR388 capsule

Placebo Comparator: Placebo bid Drug: Placebo capsule

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.

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

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).

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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

Key Inclusion Criteria:

  • Subject has probable AD dementia according to the NIA-AA criteria.
  • Subject has an MMSE score 12 and 24 inclusive at both screening and Visit 2 and a ≤3-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 <38 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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03823404

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Sponsors and Collaborators
Cortexyme Inc.
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Responsible Party: Cortexyme Inc. Identifier: NCT03823404    
Other Study ID Numbers: COR388-010
First Posted: January 30, 2019    Key Record Dates
Last Update Posted: October 23, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders