Case Study | Complex Innovative Designs
Bayesian Trial Design to Generate Evidence of the Safety and Efficacy of a Drug Regimen
A biotech company sought support in the design of their Phase II clinical trial to test the safety and efficacy of a novel inhibitor in combination with Pembrolizumab in patients with Head and Neck Squamous Cell Carcinoma (HNSCC).
A biotech company sought to investigate the efficacy of a novel inhibitor in combination with Pembrolizumab in patients with HNSCC. The Phase II study data suggested that with daily dosing in the efficacious range, the combination therapy may increase Grade-3 Hepatic toxicities.
For this reason, the biotech desired support in the design of their Phase II clinical trial to test for safety and efficacy with intermittent dosing in the efficacious range of the combination therapy compared to Pembrolizumab monotherapy. The client wanted to find the right balance between toxicity and efficacy, and to select the best dose as early as possible during the intermittent analysis. They also expected the trial to generate evidence necessary for securing new investments and partnerships for Phase III.
Alira Health proposed a Bayesian design which boosted statistical efficiency and allowed two to one randomization. We developed and executed a six-month project plan in close collaboration with the biotech company’s Chief Medical Officer and their Clinical, Regulatory, and Strategy teams.
Our expert biostatistician acted as part of the biotech’s team and implemented the following project steps:
- Existing preclinical and clinical data review
- Literature review – focused on existing trial data to compute hazard rate (progression free survival and overall survival) prior for the standard of care arm for Bayesian borrowing
- Simulation-guided design, computation of sample size, and pre-specification of design parameters
- Protocol writing
- Development of Statistical Analysis Plan
- Briefing package for the Food and Drug Administration (FDA) and response to the FDA’s written feedback
Alira Health successfully delivered a complex Phase 2A/2B Seamless Bayesian design. The design incorporated historical data and fully considered the company’s pain points, including patient recruitment, randomization ratio, and treatment toxicity.
Following the project, the biotech company chose a regimen that considered both toxicity and efficacy of the product. Alira Health helped to generate evidence of the safety and efficacy of this regimen.
The integrated multiple interim looks also served as inflection points to attract further investments and partnerships for Phase 3.
Finally, the FDA’s written response suggested that early approval may be possible depending on the data. However, a Phase II trial that does not incorporate historical data would be needed in the future for full approval.
Key Success Factors
Alira Health’s unique expertise in Complex Innovative Designs allowed to deliver a solution that fit the biotech company’s needs. Our team contributed a unique blend of expertise in simulated innovative designs and Bayesian statistics. Alira Health’s ability to act as part of the company’s team also proved crucial to the success of this project.
The delivery of a Phase II design that incorporated historical data and full consideration of the company’s pain points enabled the client to select a regimen that considered both toxicity and efficacy of the product and to generate evidence of the safety and efficacy of this regimen. The integrated multiple interim looks also served as inflection points to attract further investments and partnerships for Phase 3.