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

NCT ID: NCT03823404

Last Updated: 2023-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 643 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-28
• Study Completion Date: 2022-01-01

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.

Conditions

Alzheimer Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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

Group Type: EXPERIMENTAL

COR388 capsule

Intervention Type: DRUG

BID (twice daily)

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

Group Type: EXPERIMENTAL

COR388 capsule

Intervention Type: DRUG

BID (twice daily)

Placebo BID

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

Group Type: PLACEBO_COMPARATOR

Placebo capsule

Intervention Type: DRUG

BID

Interventions

COR388 capsule

BID (twice daily)

Intervention Type: DRUG

Placebo capsule

BID

Intervention Type: DRUG

Other Intervention Names

atuzaginstat; atuzaginstat

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cortexyme Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen Smith, MD

Role: STUDY_DIRECTOR

Quince Therapeutics Inc

Locations

Xenoscience, Inc.

Phoenix, Arizona, United States

Banner Alzheimer's Institute

Phoenix, Arizona, United States

Banner Sun Health

Sun City, Arizona, United States

ATP Clinical Research, Inc.

Costa Mesa, California, United States

Alliance Research

Long Beach, California, United States

Standford University

Palo Alto, California, United States

CITRIALS

Riverside, California, United States

CITRIALS

Santa Ana, California, United States

Syrentis Clinical Research

Santa Ana, California, United States

Southern California Research LLC

Simi Valley, California, United States

JEM Research Institute

Atlantis, Florida, United States

Brain Matters Research

Delray Beach, Florida, United States

Neuropsychiatric Research Center of Southwest Florida

Fort Myers, Florida, United States

MD Clinical

Hallandale, 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

Future Care Solutions, LLC

Miami, Florida, United States

Miami Dade Medical Research Institute

Miami, Florida, United States

Sensible Healthcare LLC

Ocoee, Florida, United States

Bioclinica Research

Orlando, Florida, United States

Anchor Neuroscience

Pensacola, Florida, United States

Suncoast Neuroscience Associates, Inc.

St. Petersburg, Florida, United States

Brain Matters Research at the Kane Center

Stuart, Florida, United States

Stedman Clinical Trials

Tampa, Florida, United States

Columus Memory Center

Columbus, Georgia, United States

NeuroStudies.net, LLC

Decatur, Georgia, United States

Northwest Clinical Trials

Boise, Idaho, United States

Alexian Brothers Neurosciences Research

Elk Grove Village, Illinois, United States

Ascension Via Christi Research

Wichita, Kansas, 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

Memory Center

Hattiesburg, Mississippi, United States

Cleveland Clinic Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Princeton Medical Institute

Princeton, New Jersey, 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

Albuquerque Neuroscience

Albuquerque, New Mexico, United States

Disease Research & Neurology Center of Neurological Associates of Albany

Albany, New York, United States

Integrative Clinical Trials LLC

Brooklyn, New York, United States

Spri Clinicaltrials, Llc

Brooklyn, New York, United States

Mid Hudson Medical Research

New Windsor, New York, United States

ANI Neurology, PLLC dba Alzheimer's Memory Center

Charlotte, North Carolina, United States

Insight Clinical Trials, LLC

Beachwood, Ohio, United States

Neurology Diagnostics Inc.

Dayton, Ohio, United States

Memory Health Center at Summit Research Network

Portland, Oregon, United States

Northeastern Pennsylvania Memory and Alzheimer's Center

Plains, Pennsylvania, United States

Senior Adults Specialty Research

Austin, Texas, United States

Kerwin Research Center

Dallas, Texas, United States

Neurology Consultants of Dallas

Dallas, Texas, United States

Houston Methodist Department of Neurology

Houston, Texas, United States

Clinical Trial Network

Houston, Texas, United States

University of Virginia Adult Neurology

Charlottesville, Virginia, United States

Recognition Health

Fairfax, Virginia, United States

Northwest Clinical Research Center

Bellevue, Washington, United States

UW Alzheimer's Disease Research Center

Seattle, Washington, United States

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, United States

Hôpital de Brabois

Toulouse, Cedex, France

Centre de Ressources Biologiques

Lille, , France

University Hospital La Timone, Department of Neurology and Neuropsychology

Marseille, , France

Service de Gériatrie

Nice, , France

Hôpitaux Universitaires de Strasbourg, Centre d'Investigation Clinique, Hôpital Hautepierre

Strasbourg, , France

CHRU de Nancy Hôpital de Brabois Service de Gériatrie

Vandœuvre-lès-Nancy, , France

Brain Research Center Den Bosch B.V.

's-Hertogenbosch, , Netherlands

Brain Research Center

Amsterdam, , Netherlands

PreCare Trial & Recruitment

Beek, , Netherlands

Isala Zwolle - Interne geneeskunde Centrum voor ouderengeneeskunde

Zwolle, , Netherlands

Brain Research Center Zwolle

Zwolle, , Netherlands

Indywidualna Specjalistyczna Praktyka Lekarska

Gdansk, , Poland

NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS

Katowice, , Poland

Krakowska Akademia Neurologii

Krakow, , Poland

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Siemianowice Śląskie, , Poland

Euromedis Sp. z o.o.

Szczecin, , Poland

Centrum Medyczne NeuroProtect

Warsaw, , Poland

NZOZ Wrocławskie Centrum Alzheimerowskie

Wroclaw, , Poland

Policlinica Gipuzkoa

San Sebastián, Gipuzkoa, Spain

Hospital General de Alicante

Alicante, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Fundacio Ace

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Ramón Y Cajal

Madrid, , Spain

Hospital Universitari General de Catalunya

Sant Cugat del Vallès, , Spain

Hospital Universitario Marqués de Valdecilla

Santander, , Spain

Cognition Health Birmingham (private)

Edgbaston, Birmingham, United Kingdom

St Pancras Clinical Research (private)

Barbican, London, United Kingdom

Cognition Health Plymouth

Plymouth, Science Park, United Kingdom

Memory Assessment and Research Centre, Moorgreen Hospital

Southampton, UK, United Kingdom

RICE - The Research Institute for the Care of Older People

Bath, , United Kingdom

Glasgow Memory Clinic

Glasgow, , United Kingdom

Cognition Health Ltd. (private) Guildford

Guildford, , United Kingdom

Cognition Health Ltd. (private) London

London, , United Kingdom

Kingshill Research Centre Swindon

Swindon, , United Kingdom

Countries

United States; France; Netherlands; Poland; Spain; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

COR388-010

Identifier Type: -

Identifier Source: org_study_id