Safety Study of CN-105 Neuroprotective Peptide for Intracerebral Hemorrhage
Condition: Intracerebral Hemorrhage (ICH)
MeSH terms: Cerebral Hemorrhage; Hemorrhage
Study type: Interventional
Phase: Phase 1

Summary: 
      This study evaluates the safety, tolerability, and pharmacokinetics (PK) of a single
      escalating dose and repeated doses of CN-105 in healthy adult participants. There will be
      about 48 subjects, 36 active and 12 placebo.
    

Detailed description: 
      Intracerebral hemorrhage (ICH), which is often associated with longstanding hypertension,
      affects as many as 50,000 people annually in the United States alone. ICH remains associated
      with poor outcome, and approximately 40 to 50% of afflicted patients will die within 30 days.
      Unfortunately, little improvement has been made in the ICH-associated mortality rate over the
      last 20 years. To address this issue, the National Institutes of Health issued a priorities
      report in 2005, and the American Heart Association released a recent set of clinical
      guidelines for the first time in nearly a decade. In these reports, the importance of
      developing clinically relevant models of ICH that will extend our understanding of the
      pathophysiology of the disease and target new therapeutic approaches was emphasized. At
      present, however, there are no proven neuroprotective pharmacological treatments for ICH or
      other forms of acute brain injuries, such as traumatic brain injury (TBI) and subarachnoid
      hemorrhage (SAH).

      To meet this unmet medical need, CereNova, LLC has developed a novel therapeutic approach
      based on the known biological function of endogenous apolipoprotein E (apoE), a key mediator
      of the neuroinflammatory response and recovery from a variety of acute and chronic brain
      injuries1-5. There are three common human isoforms of apolipoprotein E, designated apoE2,
      apoE3, and apoE4, which differ by single cysteine to arginine substitutions at positions 112
      and 158. Although originally defined in the context of cholesterol metabolism, apoE is also
      produced in the brain, where it modulates neuroinflammatory responses and functional outcomes
      after injury in an isoform specific fashion1. Specifically, the apoE3 protein isoform plays
      an adaptive role in downregulating glial activation and reducing secondary neuronal injury,
      whereas the E4 isoform is associated with increased neuroinflammation and poor functional
      outcomes.

      Although the intact apoE holoprotein does not cross the blood brain barrier (BBB) and thus
      cannot be administered therapeutically, we have previously demonstrated that smaller apoE
      mimetic peptides do effectively cross the BBB while effectively downregulating the brain
      inflammatory responses in vitro and in vivo6. CN-105, CereNova's lead clinical candidate, is
      a small, 5 amino acid apoE-mimetic peptide that is derived from the receptor binding region
      of apoE. CN-105 retains the anti-inflammatory and neuroprotective effects of intact apoE, is
      well tolerated in preclinical studies, and readily crosses the BBB to effectively reduce
      inflammatory responses in the brain.
    

Intervention name(s): CN-105; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Single and multiple intravenous (IV) doses of CN-105; Normal Saline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment