Phase 3 Trial of Therapy for Inflammation, Insulin-sensitivity in Alzheimer’s to Open
NeurMedix has announced it will soon open a pivotal Phase 3 clinical trial of its lead investigational therapy, NE3107, for people with Alzheimer’s disease, following authorization by the U.S. Food and Drug Administration (FDA).
The trial (NCT04669028), to be conducted at about 30 clinical U.S. sites, will be looking to recruit up to 316 people with mild to moderate Alzheimer’s. The process has not yet started, but NeurMedix expects to enroll the first patient in May. Contact information for those interested is available here.
“The FDA’s authorization of this pivotal phase 3 clinical trial is an important milestone in our pursuit of a life changing, safe, and efficacious intervention for this largest unmet medical need,” Terren Peizer, founder, chairman and CEO of NeurMedix, said in a press release.
Increasing evidence supports inflammation and insulin resistance — a condition in which cells no longer respond to the action of insulin, a hallmark of type 2 diabetes — playing a role in Alzheimer’s development. Inflammation and a defective insulin response lead to a poor uptake of sugar (glucose) by brain cells, affecting their normal function, and possibly to Alzheimer’s dementia and progression.
“It is well-known that insulin resistance predicts neuroinflammation, and cognitive decline, and that up to 81% of Alzheimer’s disease patients have impaired glucose tolerance or type 2 diabetes,” Peizer said.
Despite the established role of inflammation in the disease, however, approved anti-inflammatory agents are ineffective, either due to their inability to cross the blood-brain barrier and reach the brain, or because they lack broad anti-inflammatory activity. (Of note, the blood-brain barrier is a highly selective membrane that shields the central nervous system from circulating blood.)
NE3107 is a small molecule, oral treatment designed to act as an anti-inflammatory and insulin-sensitizing agent. It works by targeting three major inflammation signaling pathways, those controlled by the extracellular signal regulated kinase (ERK), nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB), and tumor necrosis factor (TNF).
In clinical studies of people with type 2 diabetes, NE3107 inhibitory activity of ERK and NF-κB lessened insulin resistance and lowered the levels of C-reactive protein, a marker of systemic inflammation.
NeurMedix believes that NE3107’s ability to reach the brain, allied with its ability to halt inflammation without additional immunosuppressive effects, makes it an attractive possibility for Alzheimer’s.
“Inflammation-driven systems dysregulation has been well-described in Parkinson’s and Alzheimer’s diseases,” said Christopher Reading, PhD, chief scientific officer of NeurMedix. “Our previous findings that NE3107 decreases system dysregulation should bode well for the Phase 3 trial.”
In the trial, people with mild to moderate Alzheimer’s (age range, 55 to 85) will be randomly assigned to 20 milligrams (mg) of NE3107 or a placebo capsule, twice a day for 30 weeks. Those assigned to the treatment arm will receive increasing doses of NE3107 over the first four weeks (starting at 5 mg), reaching the 20 mg dose by week five.
The study’s main goals include changes in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) and the Alzheimer’s Disease Study Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC), which measure cognitive function and cognitive functional and behavioral characteristics, respectively.
Tests for neuropsychological problems, glucose levels, and inflammation will also be assessed as additional (secondary) goals.
“We believe NE3107 reduces neuroinflammation and restores insulin sensitivity, and thereby may halt the progression of Alzheimer’s disease. Of the four indications that we hope to pursue in the coming year, we believe that the application of NE3107 to Alzheimer’s disease has a very high probability of success as it uniquely addresses all of the known pathways of Alzheimer’s disease,” Peizer said.
People with cognitive impairment due to medical conditions other than Alzheimer’s will not be included in this study, which is expected to conclude in January 2023.
The trial’s design was developed in collaboration with Worldwide Clinical Trials (Worldwide), a global contract research organization led by Michael Murphy, MD, PhD. Murphy, who serves as the chief medical and scientific officer of Worldwide, has more than 30 years of experience in Alzheimer’s drug development and clinical trial design.