A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2A CLINICAL TRIAL OF NA-831 IN PATIENTS WITH MCI AND EARLY ONSET ALZHEIMER’S DISEASE

Abstract

Preclinical experiments indicate that NA-831 is an endogenous small molecule that exhibits neuroprotection, neurogenesis, and cognitive protective properties across a range of disease models. NA-831 has been shown to be safe and well tolerated in healthy volunteers. A randomized clinical trial of NA-831 was performed in a total of 56 patients: 32 Alzheimer patients with MCI, and 24 patients with early onset of Alzheimer's disease. The patients with MCI received 10 mg of NA-831 or placebo orally per day. The patients with early onset of Alzheimer's disease received 30 mg of NA-831 or placebo orally per day. Randomization was performed by a centralized Interactive Voice and Web Response System. The study was conducted in accordance with the Declaration of Helsinki and ICH and GCP guidelines. All patients provided written informed consent. Inclusion criteria included: (a) male or female, at 55–80 years of age at screening, (b) For MCI patients, MMSE score ≥20. For patients with early onset Alzheimer's disease, MMSE score> 17 (d) Center for Epidemiological Studies-Depression (CES-D) score <27. Patients were randomly assigned to NA-831 at a daily dosage of 10 mg- 30 mg or matched placebo (1:1). The primary outcome measures were the changes in ADAS-cog, brief cognitive rating scale (BCRS) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 48 weeks. Based on the BCRS, the effects of NA-831 were apparent after 12 weeks of treatment (p=0.001), with the significant improvement in: fatigue, anxiety, irritability, affective lability, disturbance to waking, daytime drowsiness, headache, and nocturnal sleep. NA-831 showed a significant improvement for patients with mild and moderate AD with the ADAS-Cog score changed of an average of 3.9 as compared to the placebo (NA-831 change −4.7 vs. placebo −8.6; P = 0.001; ITT). CIBIC-Plus showed 79.3% vs. 21.7 % patients improved; P = 0.01; ITT). NA-831 was well-tolerated at high dosage up to 50 mg per day. No adverse effects were reported. Over the 48 week treatment period, NA-831 was effective for improving cognitive and global functioning in patients with mild cognitive impairment. As an endogenous compound, NA-831 is well-tolerated and has excellent safety profile.