Pivotal NDA submission trial in ALS

The pivotal NDA Protocol required up to 50% subjects enrolled into the study with no previous exposure to the intravenous (IV) formulation of study drug. ICON had to select those countries where the IV formulation was not approved whist ensuring there were a sufficient number of central IRB sites to ensure key recruitment milestones were met.

The team encountered several site activation barriers related to the required multi-step process for pre-qualification, the large number of rater trainings and many assessments, and the long contract negotiation timelines due to multiple academic sites selected in the US. In addition, enrollment in the US and Japan was halted after receiving initial approvals due to the COVID-19 pandemic and were key contributors to enrollment.

The goal was to have first patient in (FPI) in 2019. ICON identified three sites with fast start up to meet this milestone. In order for sites to be activated there were many requirements and the study team managed the complete activation process via a Greenlight tracker, which aided in helping sites to expedite the site activation process.

After COVID-19 paused enrollment in the US and Japan, the team put in mitigation plans to ensure continuation of enrollment during the pandemic. This allowed the remaining countries to continue working on obtaining study approvals during the lull in enrollment. Once the COVID plan was in place, the remaining countries opened and all six countries were competitively enrolling.

An oral formulation of study drug for treatment was delivered to the patients at home versus the initial IV formulation, which required the patients to go to the clinic to be infused every month for 14 days. During the lull, the US and Japan had patients waiting for sites to re-open post COVID-19. Home Health was added post COVID to assist patients who could not go to clinic due to COVID related issues; patient travel reimbursement system was in place from outset as well as training support throughout the study for common issues/challenges. Ensuring each site had a strong site support plan was key to the site’s performance.

Patients were very interested in this trial, as only one standard of care IV compound for ALS had been approved in the past. This IV compound had to be administered as a 60-minute IV infusion for 14 days and then followed by a 14-day drug free period. This study gave patients an easy administration route and the ability to take the study drug orally at home for 14 days rather than going to the clinic whilst avoiding the risk of exposure to COVID-19 and its consequences. An open-label extension study to support all patients who wish to continue participation was made available.

The original objective was to enroll 150 patients in 60 sites. Patient and site demand was so high that all the patients who were screened were allowed to enroll which led to 185 patients enrolled.

Patient recruitment continued during the COVID -19 pandemic and increased substantially in July 2021 with 33% of the total of required patients enrolled in October 2021. The US and Japan exceeded their targets becoming the highest performing recruiters of the study. Last patient in was achieved as per the initial goal in November 2021.