Last week, the First-in-Human study with 2B3- 201, to-BBB's second product, was initiated at the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands. This Phase I trial is designed to determine the safety profile, and will also give a first glance at the pharmacological profile. In this double-blind crossover study, 18 healthy volunteers are assigned to three cohorts in which they will receive an ascending single dose of 2B3-201, as well as placebo and standard of care methylprednisolone.
2B3-201 is being developed for treatment of diseases with neuroinflammation, such as acute relapses of multiple sclerosis (MS). The current standard of care methylprednisolone is effective, yet it requires high dose infusions for several days. This often results in side effects and inconvenience for the patient. Therefore, there is a high medical need for an effective treatment that could be given at lower doses with a more convenient dosing regimen.
"to-BBB's G-Technology® provides a safe method to enhance the slow and sustained delivery of drugs to the brain," says Werner Gladdines, Head of Development at to-BBB. "By combining this technology with methylprednisolone, 2B3-201 was developed and tested in nonclinical models with neuroinflammation, in which it showed a similar efficacy at single administration with a 10 times lower dose compared to multiple high doses of methylprednisolone."
Following an extensive nonclinical development program, to-BBB initiated the Phase I clinical trial. The aim of this First-in-Human study is to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of 2B3-201 in healthy volunteers, in comparison to placebo and methylprednisolone. Using a double-blind crossover design, each healthy volunteer receives an infusion of 2B3-201, placebo and methylprednisolone with 1-week intervals, thereby acting as his own control.
"Next to the standard safety parameters and pharmacokinetics, assessments of effects on cognition, behavior, and glucose tolerance will be evaluated," adds Dr. Geert Jan Groeneveld, Research Director Neurology & Pain at CHDR. "By including specific neurological tests in CHDR's NeuroCart and therapeutic dose levels of methylprednisolone in the control arm, this study allows for an extensive read-out of pharmacological and neurological effects."
2B3-201 is expected to follow a relatively short route towards marketing authorization. In addition to acute MS relapses, there is significant therapeutic potential in related inflammatory diseases, such as optic neuritis, neuromyelitis optica (NMO), uveitis, Behçet's disease, sarcoidosis, and neuropathic pain.