First Human Studies of a Chimeric Anti-Methamphetamine Monoclonal Antibody

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 achievable goal of this project is to perform the first studies in humans of a new medicine, a novel anti-METH monoclonal antibody (mAb) that can selectively and quickly bind METH in the blood and prevent it from entering the brain where it causes addiction. This antibody-based medicine, designated ch-mAb7F9, is already engineered into a human-mouse chimeric form (KD for METH = 9 nM) that should be safe for human use. The investigators think 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 at succeeding with recovery. Anti-drug mAb medications have major advantages for addiction therapy given that 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. For the research and testing program, ch-mAb7F9 will be tested in humans for safety in a Food and Drug Administration (FDA)-approved trial. A highly experienced, transdisciplinary academic and industry team will accomplish the following Specific Aims: 1) execute an established regulatory strategy by obtaining FDA approval to perform a Phase 1a safety trial of ch-mAb7F9 in humans, and complete the development plan for Phase 1b studies of the interaction of ch-mAb7F9 with METH; 2) complete the analytical and manufacturing processes necessary to support the Phase 1a study; and 3) determine the safety and pharmacokinetics of ch-mAb7F9 in humans in a first-in- human study. Ch-mAb7F9 is in production and will be formulated for administration at the time of funding of this proposal. Furthermore, the production and testing processes required for a successful Investigational New Drug application are already validated through a previous successful pre-IND meeting for a similar anti-phencyclidine addiction mAb. This safety study will be crucial for determining effective human dosing regimens for follow up Phase 1b interaction studies of the safety of ch-mAb7F9 in combination with METH, and Phase 2 efficacy trials of ch-mAb7F9. The therapeutics 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. PUBLIC HEALTH RELEVANCE: This project is designed to conduct the first studies in humans of an innovative, new antibody medicine designed to block methamphetamine effects while patients undergo the long process of recovery from methamphetamine addiction. In this project, an anti-methamphetamine monoclonal antibody will be tested to determine its safety and its potential for effectiveness. This innovative medication: i) could provide an essential missing component of standard drug-abuse treatment programs; ii) has the potential to reduce the devastating behavioral and societal effects of methamphetamine abuse; and iii) therefore should improve public health.