Multinational phase 1 study for a biosimilar product

A sponsor approached ICON to conduct a first of its kind, multinational biosimilar phase 1 study for multiple sclerosis (MS). This study was performed under high regulatory scrutiny and challenging COVID-19 pandemic conditions which interrupted operations early on. During this time the sponsor acted on FDA feedback and a recalculation of sample size was made, resulting in the need to dose an additional 25% of healthy volunteers. This study expansion required additional site activation to meet the increased dosing targets. ICON’s experience, bioanalytical capabilities, recruitment processes and site activation strategies, coupled with dedicated data management and biostatistics teams, delivered the trial successfully within the sponsor’s tight timeframe

The biosimilar study commenced in late 2019 with the enrolment of 144 subjects. It was then interrupted by the COVID-19 pandemic, which halted dosing and thereby increased time pressures for study completion. Following FDA recommendations, the sponsor decided to recalculate the cohort sample size and increased it by 25%. In response, ICON had to quickly scale the study sites from three to six. Upon the study’s restart the 308 remaining subjects had to be enrolled and randomised within just four months to meet sponsor timelines.

This first of its kind MS biosimilar study also garnered regulatory attention, resulting in five of the six clinical sites and two bioanalytical laboratories being audited by the FDA. All regulatory requests had to be accommodated in a well-coordinated and timely manner to avoid delays.

ICON selected two additional sites in the US and one in Poland, all with the right capacity and highest potential for recruitment, and then executed a targeted multi layered approach for fast-paced enrolment, including precise language for effective and efficient, targeted recruitment. Master project plans were implemented to ensure consistent operations across all sites, supplemented with training and mock dosing that mitigated potential between-site variability. These master plans were supported by a unique lead role structure, including lead clinical study manager and Principal Investigator (PI) who collaborated closely with their site-specific counterparts to ensure continuity and consistency during the fast-paced scaling of this program.

ICON’s clinical pharmacology and bioanalytical facilities harmonised operating procedures and data platforms with sites, protecting data integrity, reducing site variability, and ensuring precision for this critical study.

Experienced clinical and regulatory experts leveraged their knowledge and best practices to ensure all sites were fully compliant and thoroughly prepared for the FDA audits of the clinical sites and bioanalytical laboratories. ICON teams engaged with regulatory auditors directly to provide everything they needed in a timely manner to avoid any delays on either side.

ICON successfully delivered this pivotal phase 1 biosimilarity study in a large sample of healthy study participants, by utilising a comprehensive selection of early phase services including co-located clinical pharmacology units, GMP pharmacy and bioanalytical testing facilities. Dedicated site teams consisting of lead project managers, study managers and pharmacists ensured harmonised processes across all locations, minimising variability to produce high quality data that was critical for this study. Despite complications from the pandemic and a significant expansion of the sample size after the study began, all additional site activation and subject recruitment was completed on time with no significant findings from the intensive regulatory audits across seven sites.

ICON’s bioanalytical laboratories also subsequently supported the testing requirements within phase 3 of this study. As a result of these efforts, this biosimilar drug for the treatment of multiple sclerosis was recently approved by both the FDA and EMA.