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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.
 
ClinicalTrials.gov Identifier: NCT03823404
Recruitment Status : Completed
First Posted : January 30, 2019
Results First Posted : February 23, 2023
Last Update Posted : February 23, 2023
Sponsor:
Information provided by (Responsible Party):
Cortexyme Inc.

Brief Summary:
This is a randomized, double-blind, placebo-controlled study that assessed the efficacy, safety, and tolerability of 2 dose levels of COR388 in subjects with a clinical diagnosis of mild to moderate Alzheimer's disease (AD) dementia.

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

Detailed Description:

This was a randomized, double-blind, placebo-controlled study that assessed the efficacy, safety, and tolerability of 2 dose levels of COR388 oral capsules in subjects with probable Alzheimer's disease (AD) dementia according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. The subject did not have other conditions or brain imaging abnormalities that could explain the symptoms of dementia. All subjects were encouraged to have lumbar punctures (LPs) (during screening, week 24 and week 48) in the absence of medical conditions that could increase the risk of the procedure in the opinion of the Investigator. Cerebrospinal fluid (CSF), saliva, and blood were analyzed for measurements of biomarkers of AD and neuroinflammation, and for the presence of bacterial deoxyribonucleic acid (DNA) of Porphyromonas gingivalis (P. gingivalis). A subset of sites monitored subjects for clinical evidence of periodontitis at baseline, 24 and 48 weeks.

The study consisted of 3 phases: a screening phase of up to 6 weeks, a treatment phase of up to 48 weeks, and a safety follow-up phase of 6 weeks.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 643 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
Actual Primary Completion Date : January 1, 2022
Actual Study Completion Date : January 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: COR388 80 mg twice daily (BID)
COR388 hydrochloric acid (HCl), 80 mg orally administered capsule, BID (twice daily) with water approximately 12 hours apart and no less than 6 hours apart
Drug: COR388 capsule
BID (twice daily)
Other Name: atuzaginstat

Experimental: COR388 40 mg BID
COR388 HCl, 40 mg orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart
Drug: COR388 capsule
BID (twice daily)
Other Name: atuzaginstat

Placebo Comparator: Placebo BID
Placebo orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart
Drug: Placebo capsule
BID
Other Name: atuzaginstat




Primary Outcome Measures :
  1. Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) [ Time Frame: Baseline to Week 48 ]
    Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) - Total Score The cognitive subscale of the ADAS (ADAS Cog11) was used as a primary efficacy measure and consists of 11 items assessing areas of function most typically impaired in Alzheimer's disease (AD): orientation, verbal memory, language, and praxis. he scale ranges from 0 to 70, with higher scores indicating greater disease severity.

  2. Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL) [ Time Frame: Baseline to Week 48 ]

    The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score is a 23-item inventory.

    The ADCS-ADL measures both basic and instrumental activities of daily living The total ADCS-ADL score ranges from 0 to 78, with lower scores indicating greater disease severity.



Secondary Outcome Measures :
  1. Clinical Dementia Rating-Sum of Boxes (CDR-SB) [ Time Frame: Baseline to Week 48 ]

    Clinical Dementia Rating-Sum of Boxes (CDR-SB) - Sum of Boxes CDR-SB is a semi-structured interview of participants and their caregivers. Participant's cognitive status is rated across 6 domains of functioning, including memory, orientation, judgment/problem solving, community affairs, home/hobbies, and personal care.

    Severity score assigned for each of 6 domains; total score (SB) ranges from 0 to 18. Higher scores indicate greater disease severity.


  2. Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 48 ]
    Change in Mini-Mental State Examination (MMSE) - Total Score Minimum Score - 0 Maximum Score - 30 Higher score means better outcome

  3. Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline to Week 48 ]

    Neuropsychiatric Inventory (NPI) - Total Score NPI assesses psychopathology in participants with dementia and other neurologic disorders.

    Total score ranges from 12 to 144; higher scores indicate greater disease severity.



Other Outcome Measures:
  1. Anti-P. Gingivalis IgG in Serum [ Time Frame: Baseline to Week 48 ]

    Anti-P. gingivalis immunoglobulin G (IgG) in serum

    Antibody levels were measured by ELISA and outcome measure are ELISA UNITS (EU)

    Lower levels represent a pharmacodynamic effect of the drug on its target


  2. Magnetic Resonance Imaging [ Time Frame: Baseline to Week 48 ]

    Change in magnetic resonance imaging - bilateral whole brain volume

    Larger volume may represent effect of the drug on its target


  3. Periodontal (or Gum) Pocket Depth [ Time Frame: Baseline to Week 48 ]

    Periodontal (or gum) pocket depth - pocket depth for only sites with depth >= 4mm.

    The primary endpoint was mean change in pocket depth from baseline to the end of the double-blind treatment period for tooth sites with depth ≥ 4mm at any time during the study. Therefore, values presented may be less than 4mm.

    Larger measure means worse outcome




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
Criteria

Key Inclusion Criteria:

  • Subject has probable AD dementia according to the NIA-AA criteria.
  • Subject has an Mini-Mental State Examination (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 ClinicalTrials.gov identifier (NCT number): NCT03823404


Locations
Show Show 93 study locations
Sponsors and Collaborators
Cortexyme Inc.
Investigators
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Study Director: Karen Smith, MD Quince Therapeutics Inc
  Study Documents (Full-Text)

Documents provided by Cortexyme Inc.:
Study Protocol  [PDF] May 17, 2021
Statistical Analysis Plan  [PDF] August 27, 2021

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Responsible Party: Cortexyme Inc.
ClinicalTrials.gov Identifier: NCT03823404    
Other Study ID Numbers: COR388-010
First Posted: January 30, 2019    Key Record Dates
Results First Posted: February 23, 2023
Last Update Posted: February 23, 2023
Last Verified: January 2023
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
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders