A Multiple Ascending Dose Study of COR388

• ClinicalTrials.gov Identifier: NCT03418688
• Recruitment Status: Completed
• First Posted: February 1, 2018
• Last Update Posted: November 7, 2018
• Sponsor: Cortexyme Inc.
• Information provided by (Responsible Party): Cortexyme Inc.

Study Description

Brief Summary:

The study is a randomized, double-blind, placebo-controlled, multiple ascending dose study to assess the safety and tolerability of ascending repeat doses of COR388 HCl in older healthy male and female subjects and a cohort of Alzheimer's disease subjects.

Condition or disease	Intervention/treatment	Phase
Alzheimer Disease	Drug: COR388; Drug: Placebo	Phase 1

Detailed Description:

The study will enroll 3 cohorts of 8 healthy subjects ≥55 and ≤80 years of age at the Clinical Pharmacology Unit (CPU) and 1 cohort of 12 AD subjects ≥55 and ≤80 years of age. Subjects in cohorts 1-3 will receive the study drug or placebo for 10 consecutive days while confined to the CPU. AD patients in cohort 4 will receive the study drug or placebo for 28 days as outpatient. Blood samples samples will be collected for pharmacokinetic measurements.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study of COR388 in Older Healthy Volunteers and Patients With Alzheimer's Disease
• Actual Study Start Date: March 6, 2018
• Actual Primary Completion Date: October 15, 2018
• Actual Study Completion Date: October 15, 2018

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: COR388; Increasing doses of COR388 will be administered for 10 days in cohorts 1-3 and for 28 days in cohort 4.	Drug: COR388; COR388 administered for 10 or 28 days.; Other Name: COR388 HCl
Placebo Comparator: Placebo; Matching placebo capsules will be administered for 10 days in cohorts 1-3 and for 28 days in cohort 4.	Drug: Placebo; Placebo administered for 10 or 28 days.

Outcome Measures

Primary Outcome Measures :

1. AUC [ Time Frame: Day 1 and Day 10 ]
   Area under the concentration-time curve
2. Cmax [ Time Frame: Day 1 and Day 10 ]
   Maximum observed drug concentration during a dosing interval
3. Tmax [ Time Frame: Day 1 and Day 10 ]
   Time to Cmax

Eligibility Criteria

• Ages Eligible for Study: 55 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Male or female subjects ≥55 years to ≤80 years of age, at the time of consent;
• Males of reproductive potential must agree to use double-barrier contraceptive measures or avoid intercourse from the first dose of study drug through 90 days after the last dose of study drug.
• Females of child-bearing potential must be non-lactating, have negative serum pregnancy test results at Screening and negative urine pregnancy test results at Day -1; agree to use double-barrier or hormonal contraceptive measures or avoid intercourse from Day -10 through 28 days after the last dose of study drug.
• Stable doses of medications used for stable chronic illnesses that are not prohibited by the protocol are allowed as long as the dose has been stable for 30 days prior to Screening, and no changes are expected during participation in the study;
• Body mass index ≥19 kg/m2 to ≤35 kg/m2 at Screening;
• Good general health as determined by medical history, physical examination, laboratory reports, and 12-lead ECG prior to enrollment;
• Non-smoker and non-tobacco user for a minimum of 6 months prior to the first admission and for the duration of the study;
• Able to swallow capsules;
• Fluent in, and able to read and comprehend, the English language;

Cohort 4 Only:

• Must have probable AD according to the NINDS-ADRD criteria; and an MMSE-2 score ≥14 and ≤25;
• Must have moderate to severe periodontitis according to the CDC-AAP criteria as determined by the study dentist during the screening oral examination;
• If applicable, have a primary caregiver willing to accept responsibility for supervising the treatment (eg, administering study drug) and assessing the condition of the subject throughout the study in accordance with all protocol requirements.
• Provide, if mentally competent and willing, written informed consent. If the subject is not able to provide written informed consent, written informed consent must be obtained from a legally authorized representative on the subject's behalf, and verbal assent may be obtained from the subject. In addition, if the subject has a caregiver, the caregiver will be required to provide written informed consent prior to the subject's participation in the study.

Exclusion Criteria:

• History or current evidence of clinically significant arrhythmia, heart failure, or hypotension in the Investigator's judgment;
• History or current evidence of clinically significant liver disease in the Investigator's judgment;
• Evidence of renal insufficiency defined as an estimated glomerular filtration rate <50 mL/min/1.73m2 at Screening;
• Subjects who received any treatment for periodontitis in the last 90 days including systemic or local antibiotics (eg, PerioChip®), scaling, root planing, or other surgical treatments;
• Uncontrolled medical or psychiatric illness, uncontrolled seizure disorder, or history of major stroke;
• Active, or recent history of, systemic infection within 30 days prior to Screening that required treatment with antibiotics for longer than 1 week;
• History or current evidence of psychiatric or emotional problems that would invalidate giving informed consent or limit the ability of the subject to comply with study requirements;
• History of systemic allergic reaction to any drug that is considered significant by the Investigator;
• History of alcohol or drug abuse or dependence within 12 months of Screening, as determined by the Investigator;
• Positive alcohol screen at Screening or on Day -1;
• Positive urine screen for prohibited drugs
• Positive blood screen for human immunodeficiency virus (1 and 2), hepatitis B surface antigen, or hepatitis C virus antibodies at Screening;
• Any conditions that, in the opinion of the Investigator, would make the subject unsuitable for enrollment, could interfere with the subject's participation in or completion of the study, or could interfere with interpretation of study results;
• Abnormal results of screening laboratory tests, ECG, or MRI of the brain deemed clinically significant by the Investigator;
• The use of any prohibited medication that cannot be stopped or replaced safely, based on the judgment of the Investigator; or
• Participation in another investigational new drug research study involving small molecule drugs within 30 days or biological drugs within 60 days prior to the first dose of study drug.

Contacts and Locations

Locations

United States, California

Pacific Research Network

San Diego, California, United States, 92103

United States, Florida

Bioclinica Research

Orlando, Florida, United States, 32806

United States, Ohio

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States, 45227

Sponsors and Collaborators

Cortexyme Inc.

More Information

• Responsible Party: Cortexyme Inc.
• ClinicalTrials.gov Identifier: NCT03418688
• Other Study ID Numbers: COR388-002
• First Posted: February 1, 2018
• Last Update Posted: November 7, 2018
• Last Verified: November 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders