Enrollment in Phase 2 Study of Cognitive Treatment Paused for Pandemic
The decision was made in light of the elevated risk this virus poses to an older patient population, and the challenges in assessing changes in cognitive skills remotely.
“In the midst of the COVID-19 global pandemic, the safety of our employees, colleagues, and patients participating in our clinical studies remains our top priority,” Norbert Riedel, PhD, president and CEO of Aptinyx, said in a press release.
People already enrolled may continue with the trial in accordance with medical guidance, the company stated, adding that updates will come “at a future date.”
NYX-458 is an oral small molecule compound that regulates the activity of N-methyl-D-aspartate (NMDA) receptors in the brain. These receptors are essential for nerve cell communication, which occur at structures called synapses located at the junction between two nerve cells.
Parkinson’s damages dopamine-producing neurons in the brain. One of dopamine’s many functions is to regulate NMDA receptors, and its loss is believed affect their regulation and, subsequently, cognition.
By controlling NMDA receptor activity, NYX-458 may help to ease or reverse cognitive impairment associated with Parkinson’s.
The randomized and double-blind Phase 2 (NCT04148391) clinical trial is evaluate the safety and tolerability of oral NYX-458 compared to placebo. Early signs of potential benefit will also be examined. It aims to enroll 135 Parkinson’s patients with mild cognitive impairment, ages 50 to 80, at sites across the U.S.
The study, which opened in December 2019, is randomly assigning patients to a daily oral dose of 10 mg, 30 mg, or 100 mg of NYX-458, or a placebo capsule, for 12 weeks. Those who complete this part then enter a two-week follow-up period.
NYX-458’s efficacy will be measured by how it affects patients’ memory, attention, executive function, visuospatial deficits, and quality of life, the company reported previously.
This Phase 2 trial was supported by positive preclinical data in a non-human primate model of Parkinson’s disease. In these animals, NYX-458 was seen to significantly increase attention, improve cognitive flexibility, and enhance working memory as quickly as one day after the administration of a single oral dose.
Importantly, the compound did not interfere with levodopa, a standard motor symptom treatment for Parkinson’s, suggesting these two therapies might be used in combination.
NYX-458’s safety, tolerability and pharmacokinetics (the way a compound moves through the body) was investigated in a placebo-controlled Phase 1 clinical trial in 62 healthy volunteers given NYX-458 in ascending doses ranging from 10 mg to 200 mg.
Results showed both safety and tolerability in these people, including a group of elderly volunteers. No serious adverse events associated with the treatment were reported.
Patient enrollment has also been paused in other Aptinyx’s clinical trials, including Phase 2b studies of NYX-2925, an investigational therapy for chronic pain in people with painful diabetic peripheral neuropathy (NCT04146896) and fibromyalgia (NCT04147858).