Clinical trial NCT03823404: GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease
Official title: GAIN Trial: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 in Subjects With Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alzheimer Disease
Lead sponsor: Cortexyme Inc.
Sponsor class: INDUSTRY
First posted: 2019-01-30
Enrollment: 643
Sex: ALL
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11)
timeFrame: Baseline to Week 48
measure: Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL)
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Clinical Dementia Rating-Sum of Boxes (CDR-SB)
timeFrame: Baseline to Week 48
measure: Mini-Mental State Examination (MMSE)
timeFrame: Baseline to Week 48
measure: Neuropsychiatric Inventory (NPI)
timeFrame: Baseline to Week 48
Other outcomes:
measure: Anti-P. Gingivalis IgG in Serum
timeFrame: Baseline to Week 48
measure: Magnetic Resonance Imaging
timeFrame: Baseline to Week 48
measure: Periodontal (or Gum) Pocket Depth
timeFrame: Baseline to Week 48
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc.
state: Arizona
city: Phoenix
country: United States
facility: Banner Alzheimer's Institute
state: Arizona
city: Sun City
country: United States
facility: Banner Sun Health
state: Arizona
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc.
state: California
city: Long Beach
country: United States
facility: Alliance Research
state: California
city: Palo Alto
country: United States
facility: Standford University
state: California
city: Riverside
country: United States
facility: CITRIALS
state: California
city: Santa Ana
country: United States
facility: CITRIALS
state: California
city: Santa Ana
country: United States
facility: Syrentis Clinical Research
state: California
city: Simi Valley
country: United States
facility: Southern California Research LLC
state: California
city: Atlantis
country: United States
facility: JEM Research Institute
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of Southwest Florida
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hialeah
country: United States
facility: Indago Research and Health Center, Inc.
state: Florida
city: Lake Worth
country: United States
facility: Alzheimer's Research and Treatment Center
state: Florida
city: Miami
country: United States
facility: Qtrials, Inc.
state: Florida
city: Miami
country: United States
facility: Future Care Solutions, LLC
state: Florida
city: Miami
country: United States
facility: Miami Dade Medical Research Institute
state: Florida
city: Ocoee
country: United States
facility: Sensible Healthcare LLC
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Pensacola
country: United States
facility: Anchor Neuroscience
state: Florida
city: Saint Petersburg
country: United States
facility: Suncoast Neuroscience Associates, Inc.
state: Florida
city: Stuart
country: United States
facility: Brain Matters Research at the Kane Center
state: Florida
city: Tampa
country: United States
facility: Stedman Clinical Trials
state: Florida
city: Columbus
country: United States
facility: Columus Memory Center
state: Georgia
city: Decatur
country: United States
facility: NeuroStudies.net, LLC
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials
state: Idaho
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Research
state: Illinois
city: Wichita
country: United States
facility: Ascension Via Christi Research
state: Kansas
city: Methuen
country: United States
facility: Activmed Practices and Research
state: Massachusetts
city: Newton
country: United States
facility: The Boston Center for Memory
state: Massachusetts
city: Quincy
country: United States
facility: Anil Nair MD, Alzheimer's Disease Center
state: Massachusetts
city: Hattiesburg
country: United States
facility: Memory Center
state: Mississippi
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo Center for Brain Health
state: Nevada
city: Princeton
country: United States
facility: Princeton Medical Institute
state: New Jersey
city: Springfield
country: United States
facility: The Cognitive Research Center of New Jersey
state: New Jersey
city: West Long Branch
country: United States
facility: Neurology Specialists of Monmouth County
state: New Jersey
city: Albuquerque
country: United States
facility: Albuquerque Neuroscience
state: New Mexico
city: Albany
country: United States
facility: Disease Research & Neurology Center of Neurological Associates of Albany
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials LLC
state: New York
city: Brooklyn
country: United States
facility: Spri Clinicaltrials, Llc
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research
state: New York
city: Charlotte
country: United States
facility: ANI Neurology, PLLC dba Alzheimer's Memory Center
state: North Carolina
city: Beachwood
country: United States
facility: Insight Clinical Trials, LLC
state: Ohio
city: Dayton
country: United States
facility: Neurology Diagnostics Inc.
state: Ohio
city: Portland
country: United States
facility: Memory Health Center at Summit Research Network
state: Oregon
city: Plains
country: United States
facility: Northeastern Pennsylvania Memory and Alzheimer's Center
state: Pennsylvania
city: Austin
country: United States
facility: Senior Adults Specialty Research
state: Texas
city: Dallas
country: United States
facility: Kerwin Research Center
state: Texas
city: Dallas
country: United States
facility: Neurology Consultants of Dallas
state: Texas
city: Houston
country: United States
facility: Houston Methodist Department of Neurology
state: Texas
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Adult Neurology
state: Virginia
city: Fairfax
country: United States
facility: Recognition Health
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Seattle
country: United States
facility: UW Alzheimer's Disease Research Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc.
state: Wisconsin
city: Toulouse
country: France
facility: Hôpital de Brabois
state: Cedex
city: Lille
country: France
facility: Centre de Ressources Biologiques
city: Marseille Cedex 5
country: France
facility: University Hospital La Timone, Department of Neurology and Neuropsychology
city: Nice
country: France
facility: Service de Gériatrie
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg, Centre d'Investigation Clinique, Hôpital Hautepierre
city: Vandoeuvre les Nancy
country: France
facility: CHRU de Nancy Hôpital de Brabois Service de Gériatrie
city: Amsterdam
country: Netherlands
facility: Brain Research Center
city: Beek
country: Netherlands
facility: PreCare Trial & Recruitment
city: Den Bosch
country: Netherlands
facility: Brain Research Center Den Bosch B.V.
city: Zwolle
country: Netherlands
facility: Isala Zwolle - Interne geneeskunde Centrum voor ouderengeneeskunde
city: Zwolle
country: Netherlands
facility: Brain Research Center Zwolle
city: Gdańsk
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
city: Kraków
country: Poland
facility: Krakowska Akademia Neurologii
city: Siemianowice Śląskie
country: Poland
facility: NEURO-CARE Sp. z o.o. Sp. Komandytowa
city: Szczecin
country: Poland
facility: Euromedis Sp. z o.o.
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Wrocław
country: Poland
facility: NZOZ Wrocławskie Centrum Alzheimerowskie
city: San Sebastián
country: Spain
facility: Policlinica Gipuzkoa
state: Gipuzkoa
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Fundacio Ace
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Ramón Y Cajal
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital Universitari General de Catalunya
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Edgbaston
country: United Kingdom
facility: Cognition Health Birmingham (private)
state: Birmingham
city: Barbican
country: United Kingdom
facility: St Pancras Clinical Research (private)
state: London
city: Plymouth
country: United Kingdom
facility: Cognition Health Plymouth
state: Science Park
city: Southampton
country: United Kingdom
facility: Memory Assessment and Research Centre, Moorgreen Hospital
state: UK
city: Bath
country: United Kingdom
facility: RICE - The Research Institute for the Care of Older People
city: Glasgow
country: United Kingdom
facility: Glasgow Memory Clinic
city: Guildford
country: United Kingdom
facility: Cognition Health Ltd. (private) Guildford
city: London
country: United Kingdom
facility: Cognition Health Ltd. (private) London
city: Swindon
country: United Kingdom
facility: Kingshill Research Centre Swindon
Study officials:
affiliation: Quince Therapeutics Inc
name: Karen Smith, MD
role: STUDY_DIRECTOR
References: