Marinus Pharmaceuticals has hit pause on its phase 3 seizure clinical trial because of a disruption to the supply of clinical trial material. With the pause adding to the impact of COVID-19 on the study, Marinus has pushed back the targeted completion data of the hospital-based clinical trial by about a year.
Previously, Marinus expected to wrap the 124-subject study up in the second half of 2022, a target that represented a slight delay versus the original plan to deliver top-line data in the first half of the year. The target has now slipped to the second half of 2023. Marinus pointed to two reasons for the delay to the study of its intravenous formulation of the GABAA receptor modulator ganaxolone.
Firstly, the study is currently paused because of a supply disruption. The issue stemmed from monitoring of stability batches of the study drug, findings that led Marinus to cut the shelf life to less than the expected 24 months. Marinus made the change to meet product stability testing specifications.
The supply disruption could set the trial back by several months. Marinus is aiming to resupply clinical trial materials by the end of the second quarter. The stability findings have also prompted Marinus to try to extend the shelf life out to 24 months or longer through changes to its manufacturing process.
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Those issues are also expected to delay the start of two other trials, including the European registration study, by six months. However, the problem is limited to the intravenous formulation of ganaxolone. The oral formulation is under review at the FDA, with a decision on approval due next month.
Marinus named COVID-19 as the second cause of the delay. The phase 3 intravenous clinical trial began just as the U.S.’ second COVID-19 wave was starting in the fall of 2020 and has since contended with subsequent waves fueled by the delta and omicron variants.
“COVID-19, and most recently the omicron variant, have continued to impact hospital resources and have put a significant strain on hospital staff, particularly in intensive care units, where the RAISE trial is being conducted. This has led to slower than anticipated enrollment,” Marinus said in a statement.
Site activation is also lagging behind expectations. Marinus hailed improvements in site activation late last year, bringing the number up to 44, and aimed to have 60 sites on board by the end of 2021. The latest update states Marinus has activated 48 sites. In 2020, Marinus said it had selected 55 out of the projected 80 sites it planned to include in the trial.