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

Cortexyme

Status and phase

Completed

Phase 3

Phase 2

Conditions

Alzheimer Disease

Treatments

Drug: COR388 capsule

Drug: Placebo capsule

Study type

Interventional

Funder types

Industry

Identifiers

NCT03823404

COR388-010

Details and patient eligibility

About

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.

Full 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.

Enrollment

643 patients

Sex

All

Ages

55 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Quadruple Blind

643 participants in 3 patient groups, including a placebo group

COR388 80 mg twice daily (BID)

Experimental group

Description:

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

Treatment:

Drug: COR388 capsule

COR388 40 mg BID

Experimental group

Description:

COR388 HCl, 40 mg orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart

Treatment:

Drug: COR388 capsule

Placebo BID

Placebo Comparator group

Description:

Placebo orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart