Recruitment success in a challenging phase 1 osteoporosis biosimilar study

Although current therapies for osteoporosis are effective for many patients, a significant unmet need remains for innovative treatments that are cost-effective, enhance bone health, reduce fracture risk, and improve patient adherence.

A sponsor conducted a randomised, double-blind, controlled, parallel-group, single-dose, three-arm clinical study to evaluate and compare the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of their biosimilar for denosumab. The study enrolled 225 healthy male participants and was conducted across two ICON-owned clinical sites over a 10-month period. 

A phase 1 study was conducted to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of the biosimilar in comparison to the reference product in healthy male volunteers ages 22-55 years old at ICON’s clinical sites in Groningen, Netherlands and Budapest, Hungary.  The enrolment of these participants represented unique challenges due to the all-male requirement, Vitamin D criteria and very long study duration with many outpatient visits. ICON proactively identified key inclusion and exclusion challenges and implemented a dynamic analysis strategy to continuously monitor and address these issues throughout the study’s screening and enrolment phase. These challenges included:

A high screen failure rate: A screen failure rate of 65% prompted a thorough evaluation of contributing factors and led to the strategic reassignment of certain participants from one clinic to another, where lower failure rates were observed. The high failure rate was primarily driven by abnormal laboratory findings, irregular vital signs, and disqualifying medical histories.

Protocol constraints: The study’s lower age limit and the requirement to supplement vitamin D, due to potential treatment effects on bone density, added complexity to the screening and enrolment process.

Oral hygiene impact: One of the protocol exclusion criteria was poor oral hygiene. This emerged as one of the highest contributing factors to screening failure rates at the Budapest site, largely due to long public dental appointment wait times in Hungary. 

Having pre-identified these issues, a series of solutions were implemented to successfully enroll the required number of male participants across the two sites. Recruitment teams reached out to eligible individuals via various channels, focusing on those who met the study criteria. Enrolled participants were encouraged to refer acquaintances, supported by an informational flyer designed to facilitate peer recruitment. Additionally, individuals who had been disapproved for other studies were reviewed to assess their suitability for this trial.

To further boost engagement, ICON deployed additional recruitment efforts including email campaigns, SMS outreach, and outbound calls, ensuring a comprehensive and proactive approach to participant enrolment.

At the Budapest CRU, ICON introduced a preliminary dental assessment to evaluate volunteers’ oral health prior to full screening. This measure impacted 20–25% of volunteers, enabling early identification of ineligible candidates. As a result, screening efficiency was improved, budget resources were optimised and the overall enrolment process was streamlined.

To support participant retention across both sites, ICON sent timely reminders throughout the study and ahead of outpatient visits. These communications helped maintain engagement and ensured consistent attendance over the 10-month study duration.

Through proactive problem-solving and tailored recruitment strategies, ICON successfully achieved the recruitment target for this complex study. A total of 225 healthy male participants were enrolled across two sites—129 in Hungary and 96 in the Netherlands—with 220 completing the full study. This resulted in an exceptional 98% retention rate over a 10 month period involving multiple outpatient visits, ultimately ensuring the collection of high-quality data for this phase 1 osteoporosis biosimilar study.

ICON’s ability to swiftly identify barriers, implement site-specific solutions, and maintain participant engagement over a long study period demonstrates its deep expertise in early phase clinical research. This outcome not only ensured the sponsor’s timelines were met but also reinforced ICON’s reputation for delivering high quality early phase trials.