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A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges
Y H Joshua Chen1, Richard Gesser2, Alain Luxembourg3
1Merck & Co., Inc., Whitehouse Station, NJ, USA.
Clinical Trials (London, England)
|October 4, 2014
Summary
A seamless adaptive trial design accelerated the development of the nine-valent human papillomavirus (HPV) vaccine, improving statistical efficiency and reducing time to market for this important cancer-preventing vaccine.
Area of Science:
- Vaccinology
- Clinical Trial Design
- Oncology
Background:
- The four-valent human papillomavirus (HPV) vaccine prevents HPV types 6, 11, 16, and 18-related cancers, accounting for 70% of cervical cancers.
- A nine-valent HPV vaccine offers broader protection, covering approximately 90% of cervical cancers by including types 31, 33, 45, 52, and 58.
Purpose of the Study:
- To discuss the design rationale and implementation challenges of a seamless Phase IIB/III adaptive outcome trial for the nine-valent HPV vaccine.
- To focus on the adaptive features of the seamless Phase IIB/III design to expedite clinical development.
Main Methods:
- A seamless Phase IIB/III trial enrolled approximately 15,000 women aged 16-26.
- Part A (1240 subjects) evaluated three nine-valent HPV vaccine formulations against a four-valent HPV vaccine control.
- Part B (13,400 subjects) further evaluated the selected nine-valent HPV vaccine formulation for immunogenicity, efficacy, and safety.
Main Results:
- The seamless Phase IIB/III design was justified by existing data on the four-valent HPV vaccine and development goals for the nine-valent vaccine.
- Subjects from Part A contributed significantly to overall follow-up, maximizing trial efficiency.
- Implementation challenges included formulation selection, regulatory discussions, and assay changes for immunological endpoints.
Conclusions:
- A seamless Phase IIB/III adaptive design was successfully implemented for the nine-valent HPV vaccine outcome study.
- This adaptive design shortened the development timeline for the nine-valent HPV vaccine through improved statistical efficiency.
Keywords:
human papillomavirus vaccineRelated Concept Videos
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