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CompletedPhase 2 / PHASE3Results posted

GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease

GAIN Trial: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 in Subjects With Alzheimer's Disease

Lead sponsor

Cortexyme Inc.

Asset

COR388

Listed sites

Recruiting sites

Enrollment

643

actual

Study population

Alzheimer’s disease

Key I/E criteria

•Alzheimer's disease•MMSE ≤3•Study partner/caregiver required

Primary endpoints

•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDCOR388-010

NCT IDNCT03823404

Timeline

Milestones

Study first posted2019-01-30actual

Study start2019-03-28actual

Primary completion2022-01-01actual

Study completion2022-01-01actual

Last update posted2023-02-23actual

Results first posted2023-02-23actual

Assets

Drug assets

COR388

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age80 Years

SexAll

Healthy volunteersNot accepted

Inclusion 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

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.

Endpoints (16)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Other (unclassified)

Function / daily living

Behavior / neuropsychiatric

Neuroimaging

Global cognition

6 endpoints

Primary/protocol endpoint

Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)

Time frame:Baseline to Week 48

ADAS-Cog

descriptive

Primary/registry result

Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)

Time frame:Baseline to Week 48

ADAS-Cog

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=214 Participants	23.7	8.8
Average of Weeks 40/48n=146 Participants	26.6	12.0
COR388 40 mg BID (Twice Daily)Baselinen=211 Participants	23.4	8.6
Average of Weeks 40/48n=148 Participants	27.9	11.8
Placebo BID (Twice Daily)Baselinen=217 Participants	23.6	9.3
Average of Weeks 40/48n=187 Participants	28.4	12.2

p<0.0455mixed-effects model for repeated measure

Secondary/protocol endpoint

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

categorical status, descriptive

Secondary/protocol endpoint

Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

Time frame:Baseline to Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

categorical status, descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=214 Participants	5.7	2.6
Average of Weeks 40/48n=149 Participants	7.2	3.6
COR388 40 mg BID (Twice Daily)Baselinen=211 Participants	6.0	2.7
Average of Weeks 40/48n=150 Participants	7.2	3.4
Placebo BID (Twice Daily)Baselinen=217 Participants	5.9	2.8
Average of Weeks 40/48n=188 Participants	7.4	3.5

Secondary/registry result

Mini-Mental State Examination (MMSE)

Time frame:Baseline to Week 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=214 Participants	18.3	3.3
Average of Week 40/48n=146 Participants	16.9	5.7
COR388 40 mg BID (Twice Daily)Baselinen=212 Participants	18.4	3.2
Average of Week 40/48n=149 Participants	16.4	5.7
Placebo BID (Twice Daily)Baselinen=217 Participants	18.2	3.3
Average of Week 40/48n=186 Participants	16.2	5.9

Function / daily living

2 endpoints

Primary/protocol endpoint

Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)

Time frame:Baseline to Week 48

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Primary/registry result

Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)

Time frame:Baseline to Week 48

ADCS-Activities of Daily Living (ADCS-ADL)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=214 Participants	59.9	11.2
Average of Weeks 40/48n=149 Participants	55.4	13.9
COR388 40 mg BID (Twice Daily)Baselinen=211 Participants	60.1	11.3
Average of Weeks 40/48n=150 Participants	54.4	13.7
Placebo BID (Twice Daily)Baselinen=217 Participants	60.4	11.3
Average of Weeks 40/48n=188 Participants	55.5	14.1

p<0455Mixed Models Analysis

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Neuropsychiatric Inventory (NPI)

Time frame:Baseline to Week 48

Neuropsychiatric Inventory (NPI)

descriptive

Secondary/registry result

Neuropsychiatric Inventory (NPI)

Time frame:Baseline to Week 48

Neuropsychiatric Inventory (NPI)

descriptive

Posted result

Group	Value (mean), score on a scale	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=213 Participants	6.7	8.7
Average of Weeks 40/48n=143 Participants	10.7	13.7
COR388 40 mg BID (Twice Daily)Baselinen=212 Participants	8.2	11.2
Average of Weeks 40/48n=142 Participants	9.2	12.1
Placebo BID (Twice Daily)Baselinen=216 Participants	8.1	10.6
Average of Weeks 40/48n=182 Participants	10.4	13.9

Neuroimaging

2 endpoints

Other/protocol endpoint

Magnetic Resonance Imaging

Time frame:Baseline to Week 48

change from baseline, improvement

Other_pre_specified/registry result

Magnetic Resonance Imaging

Time frame:Baseline to Week 48

change from baseline, improvement

Posted result

Group	Value (mean), volume (CM^3)	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=198 Participants	1005154	106682
Week 48n=105 Participants	982782	111888
COR388 40 mg BID (Twice Daily)Baselinen=199 Participants	1008135	105765
Week 48n=113 Participants	987998	102961
Placebo BID (Twice Daily)Baselinen=202 Participants	1001711	111145
Week 48n=141 Participants	986119	111779

Other (unclassified)

4 endpoints

Other/protocol endpoint/low confidence

Anti-P. Gingivalis IgG in Serum

Time frame:Baseline to Week 48

descriptive

Other/protocol endpoint/low confidence

Periodontal (or Gum) Pocket Depth

Time frame:Baseline to Week 48

change from baseline, improvement

Other_pre_specified/registry result/low confidence

Anti-P. Gingivalis IgG in Serum

Time frame:Baseline to Week 48

descriptive

Posted result

Group	Value (mean), EU	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=213 Participants	191.6	216.8
Week 48n=130 Participants	77.8	123.2
COR388 40 mg BID (Twice Daily)Baselinen=209 Participants	202.4	214.0
Week 48n=131 Participants	110.8	184.3
Placebo BID (Twice Daily)Baselinen=212 Participants	193.1	199.5
Week 48n=167 Participants	134.4	201.0

Other_pre_specified/registry result/low confidence

Periodontal (or Gum) Pocket Depth

Time frame:Baseline to Week 48

change from baseline, improvement

Posted result

Group	Value (mean), mm	Standard deviation
COR388 80 mg BID (Twice Daily)Baselinen=79 Participants	4.04	0.75
Week 48n=39 Participants	3.67	0.92
COR388 40 mg BID (Twice Daily)Baselinen=64 Participants	4.03	0.59
Week 48n=31 Participants	3.78	0.71
Placebo BID (Twice Daily)Baselinen=77 Participants	3.74	0.66
Week 48n=54 Participants	3.57	0.61

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.