Dynamic development paths for expanding a proof-of-concept study to explore dose range

Area of Science:

• Clinical pharmacology
• Drug development
• Biostatistics

Background:

• Phase II clinical trials are critical for establishing proof of concept (PoC) and dose ranging for new drug candidates.
• Traditional Phase II trials often involve separate studies for PoC and dose ranging, potentially extending development timelines.
• Current PoC studies typically compare a high dose against a placebo, followed by extensive dose-ranging studies if successful.

Purpose of the Study:

• To propose and evaluate a novel two-stage Phase II clinical trial design.
• To generate an early signal of drug efficacy in the first stage.
• To efficiently explore the dose-efficacy relationship in the second stage based on early results.

Main Methods:

• A two-stage adaptive design is proposed for Phase II clinical development.
• Stage 1 focuses on obtaining an early efficacy signal using a high dose and placebo.
• Stage 2 employs a 'Go Fast' strategy (expanding the study with lower doses) if Stage 1 is successful, or a 'Go Slow' strategy (stopping with reduced sample size) otherwise.

Main Results:

• The proposed design allows for early assessment of efficacy.
• Adaptive 'Go Fast' or 'Go Slow' strategies enable efficient resource allocation.
• The design aims to optimize the balance between confirming efficacy and exploring the dose range.

Conclusions:

• This two-stage design offers a more efficient approach to Phase II drug development.
• It allows for timely decision-making regarding further drug investigation and dose selection.
• The adaptive nature of the design can accelerate the identification of effective drug dosages.