Clinical Trials

Clinical trials are human research studies that are designed to test the safety and efficacy of new drugs in order to gain FDA approval for their use in humans. Clinical trials are performed in volunteer patient populations after preclinical studies in animal models have been completed and shown that the drug is both safe and effective. Most clinical trials follow a standard series of stages, including Phase I, Phase II and Phase III trials. Prior to initiation of clinical trials for a particular drug, the sponsor must present its preclinical findings to the FDA through an IND (Investigational New Drug) application. More information on this process can be found at http://www.fda.gov/cder/regulatory/applications/ind_page_1.htm. If the FDA does not disapprove the IND application within 30 days, it becomes effective and Phase I trials can be initiated.

In Phase I trials, a small population of patient or healthy volunteers (20-80) is given the new drug to evaluate its safety and dose range. This phase includes trials designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of a drug. Phase I trials also normally include dose-ranging, also called dose escalation, studies so that the appropriate dose for therapeutic use can be found. The tested range of doses will usually be a fraction of the dose that causes harm in animal testing. The volunteers are monitored for any adverse reactions to the new drug that might preclude its clinical use.

In Phase II trials, the new drug is given to a larger population (20-300) of patients that have the targeted disease in order to test for both safety and effectiveness in treating the disease. Phase II studies typically use higher drug doses than the Phase I trials. When the development process for a new drug fails, it usually occurs during Phase II trials when the drug is discovered to not work as planned, or to have toxic effects.

Phase III studies are randomized controlled trials on large patient groups (300 or more patients depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current ‘standard of care” treatments. If upon completion of Phase III trials the new drug is found to provide greater benefits to the patient population than currently accepted treatments, an NDA (New Drug Application) or BLA (Biologic License Application) can be filed with the FDA for licensing of the drug for human use. More information about this process can be found at http://www.fda.gov/cder/regulatory/applications/NDA.htm.

While approval of most new drugs requires all three Phases of clinical trials, some drugs are eligible for expedited approval under the FDA’s “Animal Efficacy Rule.” This rule states that a new drug can be approved based upon its efficacy in two animal models and in-depth safety analysis in healthy human volunteers. This rule was devised since volunteer populations of patients afflicted with a targeted disease are not always available for clinical trials. For example, there is no standing population of patients with Acute Radiation Syndrome (ARS) since it is an accidental/emergency condition and it would be unethical to instigate ARS by exposing humans to high doses of radiation in order to test a new drug. More information on the “Animal Efficacy Rule” can be found at http://www.hhs.gov/nvpo/policy_reg.html. This rule has been in effect since July 1, 2002 and has been used to obtain FDA approval for vaccines now in the U.S. national strategic stockpile.

Information on all current clinical trials can be found at http://clinicaltrials.gov. or information on clinical trials being run by Cleveland BioLabs on our lead drug candidates, please use Cleveland BioLabs in the key word search tool.