Transition to Human Phase 1b Trials: Nonclinical Studies of an Anti-METH mAb

点击翻译按钮获取中文摘要

 DESCRIPTION (provided by applicant): Methamphetamine (METH) abuse causes serious medical, social, and economic harm in the USA and the world. However, to date, no medications are approved to treat METH addiction. The primary goal of this translational project is to conduct safety studies of a new medicine for METH addiction, a novel anti- METH monoclonal antibody (mAb) called ch-mAb7F9, to support the initiation of a first clinical study in METH users. Results from a Phase 1a study of ch-mAb7F9 in non-METH-using healthy subjects indicate that the antibody is safe for administration in humans. Ch-mAb7F9 was created to selectively and quickly bind METH in the blood and prevent it from entering the brain and other tissues where it causes multiple health problems, including addiction. By so doing, anti-METH ch-mAb7F9 will transform the clinical treatment of addiction by providing the first medication that can reduce METH's reinforcing properties for prolonged periods of time. There is a high rate of recidivism associated with METH use. By using a long-acting antibody antagonist to provide around-the-clock protection from METH effects, patients will be much less vulnerable to relapse to METH use and thereby have significantly improved chances for recovery. Anti-drug mAb medications have major advantages for addiction therapy since steady-state concentrations and precise control of dosing are readily achievable even in immune compromised patients, and because they will not interact with other medicines. Furthermore, mAb medications are safe for most patient populations. For the research and testing program, ch-mAb7F9 will be tested in rats for safety in combination with high, binge-like doses of METH. Additionally, METH self-administration studies in rats will be performed to answer specific questions from the FDA concerning the motivation and ability of users to overcome the antibody's stimulant blocking effects. A highly experienced, trans disciplinary academic and industry team will accomplish the following Specific Aims: 1) complete essential regulatory work in preparation for a Phase 1b study; 2) manufacture ch-mAb7F9 for necessary nonclinical and future clinical studies, 3) conduct nonclinical testing to determine safety of the interaction between ch-mAb7F9 and METH in rats, and 4) test ch-mAb7F9 in METH self-administration studies to examine the motivational aspect of drug use. These studies are necessary to prepare for a Phase 1b study in METH users that will be crucial for identifying factors that determine optimal human dosing regimens and will allow for the effective design of future clinical studies where ch-mAb7F9 efficacy is the primary endpoint. The therapeutic vision is that this medication, which can be used to initiate and continue pharmacologic treatment, will be used in combination with high quality behavioral modification programs to dramatically improve patient outcomes.