P4‐203: INTERIM BIOMARKER ANALYSES OF PHASE II STUDY DATA ON SAFETY AND EFFICACY OF GM‐CSF/LEUKINE^® IN MILD‐TO‐MODERATE AD

Abstract

Background: Mild cognitive impairment ("MCI") is defined as the "symptomatic pre-dementia stage" on the continuum of cognitive decline. Currently, no medications have proven effective for MCI. 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. Methods: A randomized Phase 2A clinical trial of NA-831 was performed in Alzheimer patients with mild cognitive impairment of vascular origin. Inclusion criteria included: (a) male or female, at 55-80 years of age at screening, (b) Mini-Mental State Exam (MMSE) score !20 (primary school) or !24 (high school or above) (d) Center for Epidemiological Studies-Depression (CES-D) score <27. A total of 56 Patients were randomly assigned to NA-831 at a daily dosage of 10 mg or matched placebo (1:1) for 24 weeks. The primary outcome measures were the changes in Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog), brief cognitive rating scale (BCRS) and clinician's interview-based impression of change plus caregiver input (CIBIC-plus) after 24 weeks. All patients were monitored for adverse events (AEs). Outcome measures were analyzed for both the intention-to-treat (ITT) population and per protocol population. Results: The effects of NA-831 on Alzheimer patients with mild cognitive impairment were measured as statistically significant reductions in scores on the BCSR, and ADAS-cog scales. Based on the BCRS, the effects of NA-831 were apparent after 8 weeks of treatment (p¼0.001), with the significant improvement in the following areas: fatigue, anxiety, irritability, affective lability, disturbance to waking, daytime drowsiness, headache, and nocturnal sleep. NA-831 showed significant improvement with the ADAS-cog score changed 3.21 points (NA-831 change À4.47 vs. placebo À1.26; P ¼ 0.001; ITT). CIBIC-Plus showed (23 [82.1%] vs. 5 [17.9%]) patients improved; P ¼ 0.01; ITT). NA-831 was well-tolerated at high dosage up to 50 mg per day. No adverse effects were reported. Conclusions: Over the 6-month 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.