“Completing the last subject enrolled in the Phase 2 study with NSI-189 for the treatment of MDD earlier than expected is a significant clinical development milestone for Neuralstem,” said Rich Daly, Chairman and CEO, Neuralstem. “We now expect results from the Phase 2 study in the 3Q of 2017, and results from the subsequent, 6-month observational study to assess NSI-189’s durability effect will be available in the first half of 2018. We are thankful to the individuals and physicians who are participating in these studies and helping us to move closer to potentially bringing this new category of treatment forward.”
The double-blind, placebo-controlled Phase 2 study randomized 220 subjects to one of three oral treatment groups: placebo, 40 mg once daily (QD), 40 mg twice daily (BID). The primary efficacy endpoint is a reduction in depression symptoms as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary endpoints encompass additional clinical outcomes including objective cognition improvement measures. The trial is evaluating subjects over a 12-week dosing period with an observational follow-up period of six months to assess NSI-189’s potential for durability of benefits after the cessation of therapy. The trial is being conducted in 12 select MDD trial sites across the United States.
“Our goal is to improve the success rate in the treatment of major depressive disorder, and fulfill the unmet medical need for effective and well tolerated therapies that work differently from antidepressants that are currently available,” said Maurizio Fava, MD, Slater Family Professor of Psychiatry at Harvard Medical School, Massachusetts General Hospital and principal investigator. “The Phase 1 data have shown that NSI-189’s biological mechanism of action may provide an alternative for the treatment of MDD, with the potential for cognitive benefits and durability effects beyond the course of treatment.”
NSI-189 is a proprietary, new chemical entity that has shown to safely alleviate depression in a Phase 1b study with MDD patients. In preclinical models, NSI-189 stimulated neurogenesis, synaptogenesis and increased hippocampal volume, all of which are believed to be effective in potentially reversing depression, enhancing cognition, and promoting neuroregeneration.
About the Trial
This Phase 2 double-blind, placebo-controlled study is testing NSI-189 in a study of 220 subjects with MDD in an out-patient setting. Inclusion criteria required subjects to have a MADRS score of 20 or greater at screening and baseline. For context, a total MADRS score of 20 to 34 is suggestive of moderate depression while a score of 35 or greater is suggestive of severe depression.
Subjects were randomized to three cohorts: NSI-189 40 mg twice daily (BID), NSI-189 40 mg once daily (QD), or placebo. After the initial screening period, the randomized portion of the trial will be 12 weeks in duration.
Subjects are being evaluated along several depression measurement scales, including the MADRS, Symptoms of Depression Questionnaire (SDQ) and the Hamilton Depression Rating Scale (HAM-D), among others. The study is 80% powered (p ≤ 0.05) to show an improvement in depression symptoms, compared to placebo, with an effect size of d=0.5. Subjects will continue to be followed for an additional six months after the 12-week trial period.
Neuralstem’s patented technology enables the commercial-scale production of multiple types of central nervous system stem cells, which are being developed as potential therapies for multiple central nervous system diseases and conditions.