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

• ClinicalTrials.gov Identifier: NCT03823404
• Recruitment Status: Completed
• First Posted: January 30, 2019
• Last Update Posted: March 9, 2022
• Sponsor: Cortexyme Inc.
• Information provided by (Responsible Party): Cortexyme Inc.

Tracking Information

• First Submitted Date: January 24, 2019
• First Posted Date: January 30, 2019
• Last Update Posted Date: March 9, 2022
• Actual Study Start Date: March 28, 2019
• Actual Primary Completion Date: January 1, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 18, 2021)

• 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.
• ADCS-ADL [ Time Frame: Baseline to Week 48 ]
  Change in Alzheimer's Disease Cooperative Study Group-Activities of Daily Living (ADCS-ADL).

Original Primary Outcome Measures (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.

Current Secondary Outcome Measures (submitted: February 18, 2021)

• CDR-SB [ Time Frame: Baseline to Week 48 ]
  Change in Clinical Dementia Rating-Sum of Boxes (CDR-SB).
• MMSE [ Time Frame: Baseline to Week 48 ]
  Change in Mini-Mental State Examination (MMSE).
• NPI [ Time Frame: Baseline to Week 48 ]
  Change in Neuropsychiatric Inventory (NPI) Total Score.

Original Secondary Outcome Measures (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).

Current Other Pre-specified Outcome Measures (submitted: February 18, 2021)

• Anti-P. gingivalis IgG in serum [ Time Frame: Baseline to Week 48 ]
  Change in anti-P. gingivalis IgG in serum.
• 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 (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.

Descriptive Information

• Brief Title: 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
• 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.

The study will consist 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
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Alzheimer Disease

Intervention

• Drug: COR388 capsule
  bid
• Drug: Placebo capsule
  bid

Study Arms

• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 18, 2021): 643
• Original Estimated Enrollment (submitted: January 29, 2019): 573
• Actual Study Completion Date: January 1, 2022
• Actual Primary Completion Date: January 1, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Subject has probable AD dementia according to the NIA-AA criteria.
• Subject has an 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.

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Male and female.

• Ages: 55 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Netherlands, Poland, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03823404
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Responsible Party: Cortexyme Inc.
• Study Sponsor: Cortexyme Inc.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Cortexyme Inc.
• Verification Date: March 2022