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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: COR388 capsule; Drug: Placebo capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 643
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Centre de Ressources Biologiques
  • Marseille Cedex 5, France, 13385
    • University Hospital La Timone, Department of Neurology and Neuropsychology
  • Nice, France, 6100
    • Service de Gériatrie
  • Strasbourg, France, 67098
    • Hôpitaux Universitaires de Strasbourg, Centre d'Investigation Clinique, Hôpital Hautepierre
  • Vandoeuvre les Nancy, France, 54500
    • CHRU de Nancy Hôpital de Brabois Service de Gériatrie
  • Cedex
    • Toulouse, Cedex, France, 31059
      • Hôpital de Brabois
• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Brain Research Center
  • Beek, Netherlands, 6191 JW
    • PreCare Trial & Recruitment
  • Den Bosch, Netherlands, 5223 LA
    • Brain Research Center Den Bosch B.V.
  • Zwolle, Netherlands, 8025 AB
    • Isala Zwolle - Interne geneeskunde Centrum voor ouderengeneeskunde
  • Zwolle, Netherlands, 8025 AZ
    • Brain Research Center Zwolle
• Poland
  • Gdańsk, Poland, 80-438
    • Indywidualna Specjalistyczna Praktyka Lekarska
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
  • Kraków, Poland, 31-505
    • Krakowska Akademia Neurologii
  • Siemianowice Śląskie, Poland, 41-100
    • Neuro-Care Sp. z o.o. Sp. Komandytowa
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z o.o.
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Wrocław, Poland, 53-659
    • NZOZ Wrocławskie Centrum Alzheimerowskie
• Spain
  • Alicante, Spain, 03010
    • Hospital General de Alicante
  • Barcelona, Spain, 8036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 8005
    • Hospital de La Santa Creu I Sant Pau
  • Barcelona, Spain, 8028
    • Fundacio ACE
  • Madrid, Spain, 28034
    • Hospital Universitario Ramón y Cajal
  • Sant Cugat Del Vallès, Spain, 8195
    • Hospital Universitari General de Catalunya
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Gipuzkoa
    • San Sebastián, Gipuzkoa, Spain, 20014
      • Policlinica Gipuzkoa
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • RICE - The Research Institute for the Care of Older People
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic
  • Guildford, United Kingdom, GU2 7YD
    • Cognition Health Ltd. (private) Guildford
  • London, United Kingdom, W1G 9JF
    • Cognition Health Ltd. (private) London
  • Swindon, United Kingdom, SN3 6BW
    • Kingshill Research Centre Swindon
  • Birmingham
    • Edgbaston, Birmingham, United Kingdom, B16 8LT
      • Cognition Health Birmingham (private)
  • London
    • Barbican, London, United Kingdom, EC2Y 8EA
      • St Pancras Clinical Research (private)
  • Science Park
    • Plymouth, Science Park, United Kingdom, PL5 8BT
      • Cognition Health Plymouth
  • UK
    • Southampton, UK, United Kingdom, SO30 3JB
      • Memory Assessment and Research Centre, Moorgreen Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85004
      • Xenoscience, Inc.
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Long Beach, California, United States, 90807
      • Alliance Research
    • Palo Alto, California, United States, 94305
      • Standford University
    • Riverside, California, United States, 92506
      • CiTrials
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Santa Ana, California, United States, 92705
      • CiTrials
    • Simi Valley, California, United States, 93065
      • Southern California Research LLC
  • Florida
    • Atlantis, Florida, United States, 33462
      • JEM Research Institute
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Fort Myers, Florida, United States, 33912
      • Neuropsychiatric Research Center of Southwest Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center, Inc.
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute
    • Miami, Florida, United States, 33144
      • Qtrials, Inc.
    • Miami, Florida, United States, 33165
      • Future Care Solutions, LLC
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare LLC
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Pensacola, Florida, United States, 32502
      • Anchor Neuroscience
    • Saint Petersburg, Florida, United States, 33713
      • Suncoast Neuroscience Associates, Inc.
    • Stuart, Florida, United States, 34997
      • Brain Matters Research at the Kane Center
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
  • Georgia
    • Columbus, Georgia, United States, 31909
      • Columus Memory Center
    • Decatur, Georgia, United States, 30033
      • NeuroStudies.net, LLC
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Neurosciences Research
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Research
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices and Research
    • Newton, Massachusetts, United States, 02459
      • The Boston Center for Memory
    • Quincy, Massachusetts, United States, 02169
      • Anil Nair MD, Alzheimer's Disease Center
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Memory Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo Center for Brain Health
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Princeton Medical Institute
    • Springfield, New Jersey, United States, 07081
      • The Cognitive Research Center of New Jersey
    • West Long Branch, New Jersey, United States, 07764
      • Neurology Specialists of Monmouth County
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Albuquerque Neuroscience
  • New York
    • Albany, New York, United States, 12208
      • Disease Research & Neurology Center of Neurological Associates of Albany
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials LLC
    • Brooklyn, New York, United States, 11235
      • Spri Clinicaltrials, Llc
    • New Windsor, New York, United States, 12553
      • Mid Hudson Medical Research
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • ANI Neurology, PLLC dba Alzheimer's Memory Center
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Insight Clinical Trials, LLC
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics Inc.
  • Oregon
    • Portland, Oregon, United States, 97210
      • Memory Health Center at Summit Research Network
  • Pennsylvania
    • Plains, Pennsylvania, United States, 18507
      • Northeastern Pennsylvania Memory and Alzheimer's Center
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research
    • Dallas, Texas, United States, 75231
      • Kerwin Research Center
    • Dallas, Texas, United States, 75243
      • Neurology Consultants of Dallas
    • Houston, Texas, United States, 77074
      • Clinical Trial Network
    • Houston, Texas, United States, 77030
      • Houston Methodist Department of Neurology
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Adult Neurology
    • Fairfax, Virginia, United States, 22031
      • Recognition Health
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Seattle, Washington, United States, 98104
      • UW Alzheimer's Disease Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: atuzaginstat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)	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.	Baseline to Week 48
Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)	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.	Baseline to Week 48

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-P. Gingivalis IgG in Serum	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	Baseline to Week 48
Magnetic Resonance Imaging	Change in magnetic resonance imaging - bilateral whole brain volume Larger volume may represent effect of the drug on its target	Baseline to Week 48
Periodontal (or Gum) Pocket Depth	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	Baseline to Week 48

Collaborators and Investigators

• Sponsor: Cortexyme Inc.
• Investigators: Study Director: Karen Smith, MD, Quince Therapeutics Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2019
• Primary Completion (Actual): January 1, 2022
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: COR388-010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No