Collaboration accelerates rare disease trial delivery

ICON is conducting a global, phase 3 clinical trial for a large pharmaceutical sponsor to evaluate potential treatment for Generalised Myasthenia gravis (gMG). This rare chronic autoimmune disorder, which affects approximately 700,000 people globally, disrupts communication between nerves and muscles, leading to skeletal muscle weakness. The sponsor’s target was to enrol 180 adult patients across 112 sites in 17 countries. ICON assigned more than 300 personnel to deliver this program which was complicated by organisational changes at the sponsor, competing clinical trials and data cleaning challenges. We delivered services across Clinical Operations, Data Management, Project Management, Programming, Safety, and Medical Monitoring functions.

Organisational disruption 

The study experienced significant organisational changes, including the acquisition of the original sponsor, which resulted in a complicated journey marked by various changes to process and study team personnel. This required agile transitional structures operating both internally and externally. 

Operational complexity 

Rare disease studies face inherent recruitment challenges, compounded by complex protocols. In this phase 3 trial, a multi-vendor environment posed further risk to site activation timelines. With competing clinical trials in the same therapeutic area, rapid startup and delivery was critical. 

Data delivery 

A substantial data cleaning backlog threatened to delay important milestones, with over a third of the global backlog originating from one country and 20% from a single site. The team also had to manage an unexpected additional database lock for data requested by the FDA at very short notice.

Collaborative change management 

ICON’s close collaboration with subject matter experts across functions kept the right expertise on the study team to avoid disruption. We also assessed and recommended a strategy for aligned outsourcing models to improve efficiency and focus on priority deliverables while simultaneously addressing quality issues. 

Clear communication 

ICON opened dedicated communication channels to support internal alignment and sponsor engagement. Site staff were actively supported through engagement tools, study rejuvenation meetings and conference-based investigator sessions. 

Site and participant-centric recruitment 

Participant-centred strategies and dedicated site support through Clinical Trial Liaisons (CTLs) and Patient Advocacy Services (OUS) helped overcome common challenges in rare disease recruitment. CTLs proactively addressed issues and engaged site staff to maintain momentum and accelerate recruitment, providing strategy and custom Site Specific Patient Recruitment Plans (SSPRP). Recruitment and retention materials tailored for sites and for participants addressed needs and deepened engagement. Because of the smaller populations inherent in rare disease groups, relevant patient advocacy organisations were identified and engaged to ensure the applicable communities had access to recruitment and educational materials. Connections made were transferred to the sponsor liaison to further develop relationships as appropriate. 

Tackling the data backlog 

ICON’s strategy to address the data cleaning backlog and keep the study on track for database locks included: 

• Appointing a dedicated Clinical Trial Manager to support vendor data cleaning and rapid site query resolution
• Daily morning meetings with line-by-line reviews of the backlog to identify and resolve bottlenecks
• In one country, five CRAs were deployed on-site for a week, working flexibly with site staff to accelerate data cleaning

Despite the complexity, the team remained focused on study execution to achieve several key milestones: 

• 111% recruitment achieved
• Last Participant Enrolled one month ahead of target
• Primary database lock achieved ahead of schedule with positive top line results
• Successful inspections from FDA, EMA, PMDA and China CDE

Looking ahead 

Our solution-oriented approach and commitment to collaboration have helped to foster a strong, trusted relationship with the sponsor. The sponsor selected ICON to work on a new sub-study, now underway, to evaluate a subcutaneous delivery route for the study drug. If successful, this will reduce clinic visits and offer a less invasive treatment option for participants.