#AAN2022 – Phase 1 Data Shows NVG-291 Safe; Trial in MS Patients Anticipated
NVG-291, an experimental therapy designed to promote nervous system repair, has so far been well tolerated in an ongoing Phase 1 study with healthy volunteers.
“The Phase 1 study is progressing very well, and we are encouraged by the data we are seeing so far,” Daniel Mikol, MD, PhD, chief medical officer of NVG-291’s developer, NervGen Pharma, said in a press release.
NervGen is expecting that results from the Phase 1 study will inform the doses used in early clinical trials in multiple sclerosis (MS), spinal cord injury, and Alzheimer’s disease that are expected to start later this year.
The findings were shared at the American Academy of Neurology 2022 Annual Meeting in Seattle, Washington, in a presentation titled, “A Placebo-Controlled Phase I Study of NVG-291 in Healthy Subjects, Targeting CNS Receptor Protein Tyrosine Phosphatase Sigma (PTPσ).”
NVG-291 is an investigational medication that modulates the activity of a specific region from the protein tyrosine phosphatase (PTP) sigma, which normally acts to “put the brakes” on systems that help the nervous system repair itself from damage.
By modulating PTP signaling, NVG-291 is expected to help promote various mechanism of nervous system repair, including remyelination — restoration of the myelin sheath that’s damaged in MS.
According to NervGen, the experimental therapy has shown promise in animal models of MS and other neurological diseases.
NervGen is currently running a Phase 1 clinical trial to test NVG-291’s safety and pharmacological properties in healthy volunteers. Interim results were presented by Mikol at the AAN meeting.
In the first portion of the trial, 37 healthy volunteers were given a single subcutaneous (under the skin) injection of a placebo or NVG-291, at doses ranging from 0.032 to 0.864 mg/kg.
Results showed the experimental treatment to be generally well tolerated, with no serious side effects reported. The most common side effects associated with NVG-291 were reactions at the injection site, such as redness, pain, or itching.
Following these early results, NervGen was cleared to start a multiple ascending dose (MAD) phase of the trial, where participants receive daily subcutaneous injections of NVG-291 or a placebo for two weeks, with an additional week of monitoring afterward. In the first MAD group, four participants received NVG-291 at a dose of 0.384 mg/kg, while two participants were given a placebo.
While results from the MAD part are still blinded — researchers don’t know which patients received the active treatment or a placebo — safety data from the first MAD group were generally consistent with findings from the earlier single ascending dose (SAD) portion. The most commonly reported side effects were injection site reactions, and no serious events were reported. Also, no noteworthy changes in vital signs or laboratory parameters have been reported.
“Following a thorough safety evaluation, including a blinded review of adverse events, vital signs and laboratory data, the Safety Review Committee approved advancing to the second MAD cohort,” Mikol said. The Safety Review Committee is a panel of outside experts who review data from the ongoing trial to ensure the safety of participants.
The second MAD cohort will also enroll six people — two will be given placebo and four will receive NVG-291 at a dose of 0.576 mg/kg, for 14 days. If all goes as expected, the third MAD cohort is expected to test NVG-291 at a dose of 0.864 mg/kg.
Pharmacological data have generally been in line with expectations. The doses being tested in the MAD cohorts are higher than corresponding doses found to be effective in the animal models of disease.
“The results we are seeing in our Phase 1 study continue to be very promising. The dose of NVG-291 administered in the first cohort is already above the highest corresponding dose found to be efficacious in animal models and is substantially higher than the lower effective doses where dramatic functional improvements were observed,” Paul Brennan, NervGen’s president and CEO, said.
“We have now proceeded to evaluate a higher dose level in the second MAD cohort and the blinded safety data observed so far are encouraging and highlight that we are a step closer to initiating the Phase 1b/2 efficacy studies in patients later in 2022,” Brennan said.
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting. Go here to see the latest stories from the conference.