ALS trial best practices ensure success amid recruitment challenges

The multinational scale of the study posed challenges during start up, specifically regarding protocol. Due to different interpretations of the protocol, some countries had extensive queries regarding use of the placebo arm in a degenerative disease. France dropped as a result, and ICON had to replace those sites. Other countries requested updates to the submitted protocol to add language related to serious adverse events.

Some competing studies in this therapeutic area had less strict eligibility criteria and shorter screening periods, which impacted recruitment. For example, FVC (forced vital capacity) at 70% at screening and randomisation and a screening period of 8 weeks were the most common causes for the increased screen failure rate. 

Some sites reported that they were not enrolling to our study as they did not want their subjects taking only placebo. There were new medications for ALS approved during the study recruitment phase which impacted enrolment. One was a medication with active substance that was prohibited per protocol and was considered a standard of care in
some participant countries and a protocol amendment was necessary to allow patients to have this medication out of the exclusion criteria.

ICON leveraged extensive experience in ALS to pre-empt many of the study’s challenges. We utilised our human expertise and proprietary artificial intelligence to select the most appropriate sites for capacity and recruitment ability. We increased site engagement with MSL / CTL engagement at the start, motivational and developmental engagement with key opinion leaders and sponsors, and lessons-learned roundtables to disseminate best practices.

To overcome the patient recruitment challenges, ICON started patient identification and awareness efforts as early as possible. Tailored recruitment materials and custom strategies for each site helped drive engagement across all sites and ICON focused on raising study awareness through media exposure, industry channels, and community and advocacy group outreach. Digital and physical patient recruitment materials were designed specifically for this study with an awareness of the competition, including targeted messaging.

The study itself was altered to improve recruitment: inclusion-exclusion criteria was adjusted to Inclusion criteria (IC): SVC 60-90%; EC: assisted ventilation and Exclusion criteria (EC): Edaravone use. Concierge Services were integrated to minimise travel burden for patients.

ICON delivered this large-scale international phase 3 ALS study with a higher total enrolment rate than expected:

Our ALS experience and best practices ensured the study overcame the numerous challenges presented at startup across sites and patient.