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

Phase 2

Completed

Conditions: Alzheimer Disease

Interventions: Drug: COR388 capsule
Drug: Placebo capsule

Registration Number: NCT03823404

Lead Sponsor: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 643

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
COR388 40 mg BID	COR388 capsule	COR388 HCl, 40 mg orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart
COR388 80 mg twice daily (BID)	COR388 capsule	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
Placebo BID	Placebo capsule	Placebo orally administered capsule, BID with water approximately 12 hours apart and no less than 6 hours apart

Primary Outcome Measures

Name	Time	Method
Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)	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.
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)	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.

Secondary Outcome Measures

Name	Time	Method
Neuropsychiatric Inventory (NPI)	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.
Clinical Dementia Rating-Sum of Boxes (CDR-SB)	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.
Mini-Mental State Examination (MMSE)	Baseline to Week 48	Change in Mini-Mental State Examination (MMSE) - Total Score Minimum Score - 0 Maximum Score - 30 Higher score means better outcome

Trial Locations

Locations (92): ATP Clinical Research, Inc.
🇺🇸
Costa Mesa, California, United States
Princeton Medical Institute
🇺🇸
Princeton, New Jersey, United States
Recognition Health
🇺🇸
Fairfax, Virginia, United States
Houston Methodist Department of Neurology
🇺🇸
Houston, Texas, United States
Clinical Trial Network
🇺🇸
Houston, Texas, United States
Banner Sun Health
🇺🇸
Sun City, Arizona, United States
Policlinica Gipuzkoa
🇪🇸
San Sebastián, Gipuzkoa, Spain
Euromedis Sp. z o.o.
🇵🇱
Szczecin, Poland
Brain Research Center
🇳🇱
Amsterdam, Netherlands
Centrum Medyczne NeuroProtect
🇵🇱
Warszawa, Poland
Krakowska Akademia Neurologii
🇵🇱
Kraków, Poland
Miami Dade Medical Research Institute
🇺🇸
Miami, Florida, United States
Cleveland Clinic Lou Ruvo Center for Brain Health
🇺🇸
Las Vegas, Nevada, United States
Ascension Via Christi Research
🇺🇸
Wichita, Kansas, United States
Xenoscience, Inc.
🇺🇸
Phoenix, Arizona, United States
Banner Alzheimer's Institute
🇺🇸
Phoenix, Arizona, United States
Standford University
🇺🇸
Palo Alto, California, United States
CITRIALS
🇺🇸
Santa Ana, California, United States
Alliance Research
🇺🇸
Long Beach, California, United States
Syrentis Clinical Research
🇺🇸
Santa Ana, California, United States
Southern California Research LLC
🇺🇸
Simi Valley, California, United States
Brain Matters Research
🇺🇸
Delray Beach, Florida, United States
MD Clinical
🇺🇸
Hallandale Beach, Florida, United States
Neuropsychiatric Research Center of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Indago Research and Health Center, Inc.
🇺🇸
Hialeah, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸
Lake Worth, Florida, United States
Qtrials, Inc.
🇺🇸
Miami, Florida, United States
Sensible Healthcare LLC
🇺🇸
Ocoee, Florida, United States
Future Care Solutions, LLC
🇺🇸
Miami, Florida, United States
Anchor Neuroscience
🇺🇸
Pensacola, Florida, United States
Suncoast Neuroscience Associates, Inc.
🇺🇸
Saint Petersburg, Florida, United States
Columus Memory Center
🇺🇸
Columbus, Georgia, United States
Brain Matters Research at the Kane Center
🇺🇸
Stuart, Florida, United States
NeuroStudies.net, LLC
🇺🇸
Decatur, Georgia, United States
Alexian Brothers Neurosciences Research
🇺🇸
Elk Grove Village, Illinois, United States
Memory Center
🇺🇸
Hattiesburg, Mississippi, United States
Activmed Practices and Research
🇺🇸
Methuen, Massachusetts, United States
The Boston Center for Memory
🇺🇸
Newton, Massachusetts, United States
Anil Nair MD, Alzheimer's Disease Center
🇺🇸
Quincy, Massachusetts, United States
The Cognitive Research Center of New Jersey
🇺🇸
Springfield, New Jersey, United States
Neurology Specialists of Monmouth County
🇺🇸
West Long Branch, New Jersey, United States
Mid Hudson Medical Research
🇺🇸
New Windsor, New York, United States
Integrative Clinical Trials LLC
🇺🇸
Brooklyn, New York, United States
Northeastern Pennsylvania Memory and Alzheimer's Center
🇺🇸
Plains, Pennsylvania, United States
Memory Health Center at Summit Research Network
🇺🇸
Portland, Oregon, United States
Insight Clinical Trials, LLC
🇺🇸
Beachwood, Ohio, United States
ANI Neurology, PLLC dba Alzheimer's Memory Center
🇺🇸
Charlotte, North Carolina, United States
Kerwin Research Center
🇺🇸
Dallas, Texas, United States
Neurology Consultants of Dallas
🇺🇸
Dallas, Texas, United States
University of Virginia Adult Neurology
🇺🇸
Charlottesville, Virginia, United States
Northwest Clinical Research Center
🇺🇸
Bellevue, Washington, United States
UW Alzheimer's Disease Research Center
🇺🇸
Seattle, Washington, United States
Hôpital de Brabois
🇫🇷
Toulouse, Cedex, France
Centre de Ressources Biologiques
🇫🇷
Lille, France
Brain Research Center Den Bosch B.V.
🇳🇱
Den Bosch, Netherlands
CHRU de Nancy Hôpital de Brabois Service de Gériatrie
🇫🇷
Vandoeuvre les Nancy, France
PreCare Trial & Recruitment
🇳🇱
Beek, Netherlands
University Hospital La Timone, Department of Neurology and Neuropsychology
🇫🇷
Marseille Cedex 5, France
Hôpitaux Universitaires de Strasbourg, Centre d'Investigation Clinique, Hôpital Hautepierre
🇫🇷
Strasbourg, France
Service de Gériatrie
🇫🇷
Nice, France
Brain Research Center Zwolle
🇳🇱
Zwolle, Netherlands
Indywidualna Specjalistyczna Praktyka Lekarska
🇵🇱
Gdańsk, Poland
Isala Zwolle - Interne geneeskunde Centrum voor ouderengeneeskunde
🇳🇱
Zwolle, Netherlands
NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
🇵🇱
Katowice, Poland
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱
Siemianowice Śląskie, Poland
NZOZ Wrocławskie Centrum Alzheimerowskie
🇵🇱
Wrocław, Poland
Hospital de la Santa Creu i Sant Pau
🇪🇸
Barcelona, Spain
Hospital General de Alicante
🇪🇸
Alicante, Spain
Fundacio Ace
🇪🇸
Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸
Barcelona, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸
Santander, Spain
Hospital Universitari General de Catalunya
🇪🇸
Sant Cugat Del Vallès, Spain
Cognition Health Plymouth
🇬🇧
Plymouth, Science Park, United Kingdom
Cognition Health Birmingham (private)
🇬🇧
Edgbaston, Birmingham, United Kingdom
St Pancras Clinical Research (private)
🇬🇧
Barbican, London, United Kingdom
Memory Assessment and Research Centre, Moorgreen Hospital
🇬🇧
Southampton, UK, United Kingdom
Cognition Health Ltd. (private) Guildford
🇬🇧
Guildford, United Kingdom
RICE - The Research Institute for the Care of Older People
🇬🇧
Bath, United Kingdom
Glasgow Memory Clinic
🇬🇧
Glasgow, United Kingdom
Kingshill Research Centre Swindon
🇬🇧
Swindon, United Kingdom
Cognition Health Ltd. (private) London
🇬🇧
London, United Kingdom
Bioclinica Research
🇺🇸
Orlando, Florida, United States
Stedman Clinical Trials
🇺🇸
Tampa, Florida, United States
Medical College of Wisconsin, Inc.
🇺🇸
Milwaukee, Wisconsin, United States
Northwest Clinical Trials
🇺🇸
Boise, Idaho, United States
Disease Research & Neurology Center of Neurological Associates of Albany
🇺🇸
Albany, New York, United States
JEM Research Institute
🇺🇸
Atlantis, Florida, United States
Spri Clinicaltrials, Llc
🇺🇸
Brooklyn, New York, United States
Hospital Universitario Ramón Y Cajal
🇪🇸
Madrid, Spain
Albuquerque Neuroscience
🇺🇸
Albuquerque, New Mexico, United States
Senior Adults Specialty Research
🇺🇸
Austin, Texas, United States
Neurology Diagnostics Inc.
🇺🇸
Dayton, Ohio, United States