Design and Conduct Considerations for First-in-Human Trials

Area of Science:

• Translational Science
• Drug Development
• Clinical Trials

Background:

• Advancing drug candidates from preclinical research to human testing is crucial for therapeutic development.
• First-in-human (FIH) trials are essential for determining safe dosage ranges for new drugs.
• Efficient FIH trials necessitate robust cross-functional collaboration.

Purpose of the Study:

• To provide a tutorial on conducting FIH trials for both small molecule and biologic drug candidates.
• To cover key aspects including regulatory requirements, preclinical safety, study design, safety monitoring, and biomarker assessment.
• To highlight recent European Medicines Agency (EMA) guideline revisions impacting FIH trial design and risk mitigation.

Main Methods:

• The publication serves as a tutorial, synthesizing information on FIH trial conduct.
• Emphasis is placed on critical FIH trial design elements: starting dose, study size, population, dose escalation, and adaptive designs.
• Discussion includes regulatory considerations, preclinical safety testing, biomarker assessment, and global factors.

Main Results:

• Provides a comprehensive overview of essential components for successful FIH trials.
• Details specific design considerations crucial for early-phase drug development.
• Incorporates recent regulatory updates, particularly from the EMA, to enhance trial safety and efficiency.

Conclusions:

• FIH trials are a critical step in translational science, bridging discovery and therapy.
• Careful planning and execution, informed by regulatory guidelines and design principles, are vital for FIH trial success.
• Adapting to new regulatory measures can optimize safety and mitigate risks in early-phase human testing.