Treatment with EDV2209 was considered safe and was interpreted to provide potential benefit for improving patient outcome following severe SAH, providing a rationale to continue with a Phase 2b/3 study powered to determine efficacy as well as safety.
Key Findings
Methods
The Phase 1b/2a STOP-DCI trial tested the MEK 1/2 inhibitor EDV2209 given intracerebroventricularly in patients with severe spontaneous subarachnoid hemorrhage in a first-in-human randomized, double-blind, placebo-controlled, multiple ascending-dose design.
Registered as EUCT No. 2024-514590-22-00.
Phase 1b enrolled N = 11 patients in three cohorts receiving a single ICV bolus (8.55 µg, 17-28.5 µg).
Phase 2a enrolled N = 16 patients in two cohorts receiving three ICV injections of 28.5 µg EDV2209 or placebo over 18 h.
Dosing in Phase 2a began within 8 h of SAH onset.
Results
Adverse events were equally distributed between EDV2209-treated and placebo patients, with no treatment-associated safety concerns.
The abstract reports 'an equal distribution of adverse events between treatment and placebo.'
No treatment-associated safety concerns were identified across the Phase 1b and Phase 2a cohorts.
Results
Clinical outcomes and mortality in EDV2209-treated patients were as expected or better than expected for patients with severe SAH.
The trial was designed for safety and not powered for efficacy.
Authors interpret the outcomes as indicating potential benefit of EDV2209.
Results
EDV2209 pharmacokinetics were reproducibly stable in cerebrospinal fluid, and no EDV2209 was detectable in plasma.
Stable CSF levels were seen after ICV administration.
Absence of detectable plasma levels suggests the drug remained confined to the CNS compartment.
Conclusions
The authors conclude the results support proceeding to a larger Phase 2b/3 trial powered for efficacy and safety.
Treatment was considered safe in this small first-in-human study (total N = 27).
Efficacy has not yet been established.
What This Means
This early-stage clinical trial tested a new drug, EDV2209, in people who had a severe bleed on the surface of the brain (subarachnoid hemorrhage). The drug blocks a signaling pathway (MEK 1/2) and was given directly into the brain's fluid-filled spaces. A total of 27 patients took part: 11 in an initial dose-finding phase and 16 in a second phase, in which patients received either three doses of the drug over 18 hours or a placebo, starting within 8 hours of the bleed.
The main finding was that the drug appeared safe. Side effects occurred about equally in the drug and placebo groups, and no safety concerns were linked to the treatment. The drug stayed at stable levels in the spinal/brain fluid and was not detected in the blood. Patients who received the drug had outcomes and survival that were as expected or better than expected for such severe bleeds.
Because the trial was small and designed mainly to test safety, it cannot show that the drug works. This research suggests that a larger trial is justified to find out whether EDV2209 can actually improve recovery after severe subarachnoid hemorrhage.