GAIN Trial Reaches Milestone With 500 Patients Enrolled

Cortexyme has reached a milestone after enrolling 500 patients with mild to moderate Alzheimer’s disease in its ongoing Phase 2/3 GAIN clinical trial testing the company’s investigational treatment COR388 (atuzaginstat).

Enrollment for GAIN (NCT03823404) has been open since the second quarter of 2019, with recruitment ongoing at sites in the U.S. and Europe. Data from an interim analysis — scheduled to occur after 300 patients reach 24 weeks of treatment with COR388 — is expected by the end of 2020.

A full analysis of the trial data, which will occur after all patients have reached one year of treatment, is expected by the end of 2021.

“We are gratified to see the continued high level of engagement of our clinical sites and study participants and their caregivers, especially during the last several months,” said Michael Detke, MD, PhD, chief medical officer of Cortexyme, in a press release.

Reaching the enrollment milestone, especially given the COVID-19 pandemic and its limitations, underscores both the need for an Alzheimer’s treatment and the potential therapeutic benefit of COR388, according to Cortexyme.

COR388 is designed to inhibit toxic protease enzymes, also called gingipains, produced by the bacteria P. gingivalis. Gingipain proteins have been found in more than 90% of post-mortem brain samples from Alzheimer’s patients.

Furthermore, studies using animal models have shown that the presence of gingipains can trigger Alzheimer’s pathology, prompting researchers to investigate COR388 as a treatment for the disease.

The GAIN trial seeks to recruit 573 patients from the ages of 55 to 80 with a confirmed diagnosis of mild to moderate Alzheimer’s, at several testing centers across the U.S. and Europe.

The trial is testing the efficacy, safety, and tolerability of two oral doses (80 mg or 40 mg pills, twice a day) of COR388 versus placebo.

After a six-week screening period, the treatment part of the trial lasts for a total of 48 weeks, followed by a safety follow-up period of six weeks.

Researchers will perform magnetic resonance imaging (MRI) brain scans and collect cerebrospinal fluid — that which surrounds the brain and spinal cord — saliva, and blood samples at the onset of treatment, at 24 weeks, and at 48 weeks.

The samples will be analyzed for Alzheimer’s biomarkers, neuroinflammation, and levels of P. gingivalis.

Patients will also be evaluated for changes in clinical status, including the severity of cognitive symptoms of dementia, after the 48-week treatment period.

Eligible participants who complete one year in the study may enroll in a follow-up trial where all patients will receive the candidate therapy.

The trial also includes a sub-study to evaluate the clinical benefit of COR388 in the treatment of periodontitis, a serious infection of the gums that is caused by P. gingivalis and gingipains. Of the patients enrolled so far in this sub-study (about 40% of the total GAIN trial population), more than 90% had moderate to severe periodontitis at baseline.

“We expect to complete GAIN enrollment in the next few months and look forward to sharing study results when available,” Detke said.