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

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ClinicalTrials.gov Identifier: NCT03823404
Recruitment Status : Recruiting
First Posted : January 30, 2019
Last Update Posted : November 8, 2019
Sponsor:
Information provided by (Responsible Party):
Cortexyme Inc.

Tracking Information
First Submitted Date  ICMJE January 24, 2019
First Posted Date  ICMJE January 30, 2019
Last Update Posted Date November 8, 2019
Actual Study Start Date  ICMJE March 28, 2019
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) [ Time Frame: Baseline to Week 48 ]
Mean change in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11) from baseline to the end of treatment period. ADAS-Cog 11 measures cognitive functions and non-cognitive functions such as mood and behavior. Total scores range from 0-70, with higher scores (≥ 18) indicating greater cognitive impairment. ADAS-Cog 11 score increases by 2-4 points per year on average in subjects with mild to moderate Alzheimer's Disease. A treatment period of 48 weeks was selected to allow sufficient time to demonstrate at least 2.5 points difference between active treatment and placebo on ADAS-Cog 11 at the end of the treatment period.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03823404 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2019)
  • ADCS-ADL [ Time Frame: Baseline to Week 48 ]
    Change in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL).
  • CDR-SB [ Time Frame: Baseline to Week 48 ]
    Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: January 29, 2019)
  • Mini-Mental State Examination (MMSE) [ Time Frame: Baseline to Week 48 ]
    Change in MMSE.
  • Neuropsychiatric Inventory (NPI) [ Time Frame: Baseline to Week 48 ]
    Change in NPI.
  • Cerebrospinal fluid (CSF) Porphyromonas gingivalis DNA fragments [ Time Frame: Baseline to Week 48 ]
    Change in CSF Porphyromonas gingivalis DNA fragments.
  • Winterlight Speech Assessment [ Time Frame: Baseline to Week 48 ]
    Change in Winterlight Speech Assessment.
  • Magnetic resonance imaging [ Time Frame: Baseline to Week 48 ]
    Change in magnetic resonance imaging.
  • Periodontal (or gum) pocket depth [ Time Frame: Baseline to Week 48 ]
    Change in periodontal (or gum) pocket depth.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease
Official Title  ICMJE GAIN Trial: A Randomized, Double-Blind, Placebo-Controlled Study of COR388 in Subjects With Alzheimer's Disease
Brief Summary This is a randomized, double-blind, placebo-controlled study that will assess the efficacy, safety, and tolerability of 2 dose levels of COR388 in subjects with a clinical diagnosis of mild to moderate AD dementia.
Detailed Description This is a randomized, double-blind, placebo-controlled study that will assess the efficacy, safety, and tolerability of 2 dose levels of COR388 oral capsules in subjects with probable AD dementia according to the National Institute on Aging-Alzheimer's Association (NIA-AA) criteria. The study will enroll approximately 573 generally healthy male and female subjects ≥55 and ≤80 years of age. Enrolled subjects must have a documented diagnosis of mild to moderate AD dementia. The subject should not have other conditions or brain imaging abnormalities that can explain the symptoms of dementia. All subjects will be encouraged to have LPs (during screening, week 24 and week 48) in the absence of medical conditions that can increase the risk of the procedure in the opinion of the Investigator. Cerebrospinal fluid (CSF), saliva, and blood will be analyzed for measurements of biomarkers of AD and neuroinflammation, and for the presence of bacterial deoxyribonucleic acid (DNA) of Porphyromonas gingivalis (P. gingivalis [Pg]). A subset of sites will monitor subjects for clinical evidence of periodontitis at baseline, 24 and 48 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: COR388 capsule
    bid
  • Drug: Placebo capsule
    bid
Study Arms  ICMJE
  • Experimental: COR388 80 mg bid
    Intervention: Drug: COR388 capsule
  • Experimental: COR388 40 mg bid
    Intervention: Drug: COR388 capsule
  • Placebo Comparator: Placebo bid
    Intervention: Drug: Placebo capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 29, 2019)
573
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Subject has probable AD dementia according to the NIA-AA criteria.
  • Subject has an MMSE score 12 and 22 inclusive at both screening and Visit 2 and a ≤2-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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Gender Based Eligibility: Yes
Gender Eligibility Description: Male and female.
Ages  ICMJE 55 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael J Detke, MD, PhD 415-910-5717 clincaltrials@cortexyme.com
Listed Location Countries  ICMJE France,   Netherlands,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03823404
Other Study ID Numbers  ICMJE COR388-010
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Cortexyme Inc.
Study Sponsor  ICMJE Cortexyme Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Cortexyme Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP