CC100 is a synthetic form of caffeic acid phenethyl ester (CAPE) which has been demonstrated to be neuroprotective in animal models. CAPE administration after symptom onset in the SOD1 (G93A) ALS model significantly increased post-onset survival and lifespan. CAPE prevents initiation of multiple neuronal death/injury pathways associated with mitochondrial dysfunction. No safety issues were identified in Study CC100A involving single doses of CC100 (1 to 25 mg/kg) in 18 healthy-subjects. Plasma and urine drug-levels suggest significant systemic exposure, and CSF samples indicate that CC100 penetrates into the CNS to levels equivalent to plasma. 

Single-site, randomized, double-blind, placebo-controlled, multiple-dose 7 day study of 21 subjects with probable or definite ALS, ages 18-65 years. Cohorts 1 (250 mg/day), 2 (500 mg/day), and 3 (1000mg/day). Six subjects were randomized to CC100 and 1 to placebo per cohort with assessment of safety, pharmacokinetic, and biomarkers (including plasma levels of IL-6, TREM2, MCP-1, pNfH, IL-1β, IL-7, IL-8, CRP, IFNg, VEGF, Nrf2, C5a, HSP70, FCN3, CHIT1, and HMOX1. 

1) All 21 subjects completed the study.

2) Blinded safety review of the all 3 cohorts demonstrated no significant/major toxicity.

3) Favorable correlations between biomarker plasma levels and peak plasma levels of CC100 were detected with IL-6, TREM2, MCP-1, and pNfH suggesting potential mechanisms for benefit in ALS. Levels of IL-1β, IL-7, IL-8, CRP, IFNg, VEGF, Nrf2, C5a, HSP70, FCN3, CHIT1, and HMOX1 were unchanged. 

1) CC100 has a favorable short-term safety and tolerability profile in ALS patients.

2) Changes in biomarkers IL-6, TREM2, MCP-1, and pNfH suggest potential mechanisms for benefit in ALS.

3) Treatment of ALS with CC100 warrants further study.