Background

AC-1204 is the follow-up to Accera's AC-1202/Axona medical food product. It is a proprietary, oral formulation of caprylic triglyceride, which was designed to induce a mild chronic ketosis in order to improve mitochondrial metabolism. Regional reductions in cerebral glucose utilization are an early feature of Alzheimer's disease (Reiman et al., 2004). The rationale behind AC-1204 is to boost cellular metabolism in Alzheimer's by providing a fuel alternative to glucose. Caprylic acid is metabolized into so-called ketone bodies, such as acetoacetic acid and β-hydroxybutyric acid, which can be converted to acetyl-CoA to produce energy via the citric acid cycle.

Findings

Based on clinical experience with Accera's Axona, a medical food similar to AC-1204, this new formulation entered clinical evaluation in Phase 2/3.

In December 2012, Accera withdrew ALERT, a planned six-month Phase 2/3 trial it had previously registered (NCT01211782), reportedly because it was being redesigned. 

From March 2013 to October 2016, Accera conducted NOURISH AD, a multicenter, six-month efficacy trial with an optional six-month, open-label extension. This trial enrolled 418 patients with mild to moderate AD at 82 locations in the United States. It compared the effect of once-daily administration of 40 mg of AC-1204 containing 20 mg of the active ingredient caprylic triglyceride to placebo on the Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS–Cog) in ApoE4 non-carriers. As secondary outcomes, the trial used additional cognitive, clinical, and global measures in ApoE4 non-carriers; other outcomes include overlapping measures in ApoE4 carriers plus still more cognitive and clinical measures in both carriers and non-carriers. 

In 2016, Accera started three Phase 1 studies of AC-1204 in a total of 52 healthy volunteers. One compares serum ketone body levels after administration of AC-1204 versus caprylic triglyceride oil, as well as interactions with a high-fat diet; one compares serum ketone body generation after AC-1204 mixed in water or AC-1202 in water, versus AC-1201 in Ensure; and one compares ketone body generation after a single dose of AC-1204 to similar formulations, including AC-1202. Also in 2016, Accera conducted a pilot safety study of AC-1204 in 10 people with amyotrophic lateral sclerosis.

On February 28, 2017, Accera announced that the NOURISH-AD trial had failed to detect a statistially significant difference between AC-1204 and placebo on the ADAS-cog (see company press release).

For all clinical trials on AC-1204, see clinicaltrials.gov.

Clinical Trial Timeline