ICON conducted a phase 3 multicentre, randomised, double-blind, placebo-controlled study of the efficacy, safety and biomarker effects of a compound in patients with early Alzheimer’s disease (AD) and APOE4/4 Genotype. The study encompassed 99 sites in 9 countries in the US and Europe.

The compound was an oral agent developed as a potential disease-modifying treatment for AD. It focused on early AD patients who carry the APOE4/4 genotype, and was designed according to the current regulatory guidance for trials in symptomatic patients with early AD.

ICON’s client was a small pharma company with limited research funds. The future success of the company was dependent on the study’s outcome. Sponsor involvement in study management was high and required an appropriate level of reassurance on the delivery and quality of the study.

The study aimed to enrol approximately 300 patients with a goal of having approximately 250 completers. APOE4/4 has a prevalence of 10-15% among AD patients. To identify 300 eligible APOE4/4 carrier subjects it was calculated that prescreening approximately 3,000 AD patients would be required. However, it was necessary to screen more than 6,500 patients to randomise 325 patients globally. Reaching the enrolment goals required seamless collaboration and support between all study parties and the sponsor.

ICON implemented more frequent meetings to ensure the necessary oversight and a straightforward escalation pathway to ICON management. The project manager and project director consistently managed the client relationship to maintain accuracy and transparency.

Because of the expected high number of screen failure patients, accurate site selection was crucial. Communication between the sponsor, clinical operations and sites was very frequent. This supported planning, trending of screen failures and close enrolment oversight. Each site was adequately resourced with genetic testing kits, complemented by targeted patient recruitment and retention support to optimise screening, enrollment, and retention efforts. To mitigate the risk of delayed timelines, an accelerated database lock (DBL) was implemented and an additional project manager was appointed to lead the critical schedules.

The patient recruitment and retention campaign impact on the study was enormous: 6,568
patients were screened and 325 total patients randomised. The patient strategy and campaign implemented by ICON contributed to 4,015 screened patients and 191 patients randomised.

All the contracted study milestones were met or exceeded including:

• Site ID package agreed
• Last site proposed
• Last site selected
• First submission
• First site initiation visit (SIV)
• First site activated
• First patient screened
• Database activation
• First patient randomised
• 50% SIVs was achieved 60 days early, 80% SIV (43 days early)
• Last patient randomised
• Accelerated DBL and final DBL which took place 2 days earlier than planned

Last patient out (LPO) occurred 32 days after the contracted date. However, the LPO date was based on an enrollment (randomisation) target of 300 patients and the sponsor allowed enrollment of 325 patients without adjusting the contracted LPO date. The final deliverable was 325 patients enrolled in just under the contracted enrollment date of 18 months.