Title of Study: CC100B: Safety and Tolerability of Multiple Doses in Subjects with ALS Number of Planned, Randomized Subjects: 21 Phase of Development: 1 Objectives: Primary objective: to assess the safety and tolerability of multiple doses of orally administered CC100 in subjects with amyotrophic lateral sclerosis (ALS). Secondary objectives: to determine pharmacokinetics and pharmacodynamics of CC100 in plasma after single and after multiple doses; and to determine short-term effects of CC100 on potential blood-cell ALS biomarkers. Study Design: Phase 1 double-blind, randomized, placebo-controlled multiple-dose of three CC100-dose cohorts. Approximately 18 subjects will receive CC100. Approximately 3 subjects will be randomized to placebo (across 3 cohorts). Periodic Assessment Committee safety reviews. Main Criteria for Inclusion and Exclusions: Subjects ?18 and <65 years of age and ?113 kg (250 lbs) with definite or probable stable ALS as described by the World Federation of Neurology ad hoc committee. Subjects must have forced vital capacity of >60% predicted. Riluzole is allowed, providing dose has been stable for ?30 days. Men must be willing to practice a reliable method of birth control. Women must be non- fertile or post-menopausal. Excluded are subjects who have asthma or severe drug allergies/hypersensitivity; have known or existing evidence of serious systemic or local infection; or are immuno-compromised; have lymphoproliferative disease or malignant disease; or have serious or unstable/uncontrolled illnesses (except ALS) that could interfere with the analyses of safety. Note: Participation will not exclude subjects from future CC100 studies Criteria for Evaluation: Safety Endpoints: Adverse events, blood chemistry, hematology, urinalysis, vital signs, 12-lead ECGs. Pharmacokinetic (PK)/Pharmacodynamic (PD): Plasma for CC100 concentrations (PK). Blood collected at baseline and after each subject?s last dose will be assayed for potential biomarker(s). Stored specimens will be de-identified or combined for validating diagnostic tools/assays related to ALS. Statistical Methods: A minimum of 6 subjects per CC100 dose group and 3 placebo-dosed subjects (total across cohorts) are considered sufficient to evaluate initial safety and tolerability for the cohorts. Pharmacokinetic parameter estimates will be calculated by standard noncompartmental methods of analysis. Absolute bioavailability of administration will be estimated based on the total area under the time- concentration curve (AUC0-?).
Planned future studies of CC100, a synthetic form of caffeic acid phenethylester (CAPE), will test the efficacy of the oral drug for the treatment for amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease. Administration of CAPE after symptom onset in an ALS mouse model significantly increased post-onset survival and lifespan (Fontanilla et al. 2012). Currently riluzole (Rilutek) is the only approved drug for the treatment of ALS, but it has only been shown to be effective for slowing disease progression to a modest degree (Miller et al. 2009); therefore, there is an unmet need for a drug with larger therapeutic effects (EMEA 2006). Data produced by Chemigen, LLC scientists, as well as numerous other independent investigators, show that CAPE has many potential beneficial effects which may serve to block ALS disease progression. These effects include reduced oxidative stress and inflammation (Kim et al. 2013, Mimoto et al. 2012). These parameters can be easily measured in blood to determine pharmocodynamic properties of CC100.
