First-in-human (FIH) studies are the key translational studies from preclinical to further clinical development processes.
The goal of FIH studies is to document safety and tolerability, and to investigate pharmacokinetics (PK), pharmacodynamics (PD), and appropriate dosing. These studies serve as the basis for further efficacy studies in the targeted patient populations.
Except for genotoxic/cytotoxic oncology drugs, FIH clinical studies have traditionally been conducted in healthy volunteers (HVs), which seems ideal for this type of early clinical research. However, in light of the emergence of non-cytotoxic agents (such as molecular targeting agents and immunomodulatory drugs), a number of FIH studies have recently been conducted in HVs to provide oncology indications.
This approach has been further strengthened thanks to an improved understanding of pathology, genetic alterations, animal models, and mechanisms of action of drugs.
However, early signals of development are critical to the survival of many drug development programs. With HVs, this clinical/therapeutic activity is not always possible or feasible.
During the past decade, FIH clinical trials have evolved from traditional dose and toxicity-finding studies in HVs, to innovative complex study designs - sometimes requiring patients’ involvement. Hybrid trials offer a potential solution, allowing clinical study teams to enjoy the benefits of using both HV and patients while simultaneously mitigating the potential downsides.
This white paper examines the key considerations to take into account when deciding whether to run a standard FIH in HVs, or a hybrid FIH clinical trial.