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

Alzheimer Disease Clinical Trial

Official title:

GAIN Trial: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 in Subjects With Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03823404
• Other study ID #: COR388-010
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 28, 2019
• Est. completion date: January 1, 2022

Study information

• Verified date: January 2023
• Source: Cortexyme Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 643
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• COR388 capsule
BID (twice daily)
• Placebo capsule
BID

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cortexyme Inc.

Countries where clinical trial is conducted

United States,  France,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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