BY ED SUSMAN
HOUSTON—A novel antibody, designed to inhibit destruction of the nerves involved in motor function after acute stroke, did not appear to improve outcomes when compared with placebo, researchers reported here on Wednesday at the 2017 International Stroke Conference sponsored by the American Heart Association/American Stroke Association.
The researchers wanted to examine the effects of the humanized monoclonal antibody, GSK249320, to myelin-associated glycoprotein (MAG) on motor outcomes post-stroke.
The trial randomized 134 patients to placebo or GSK249320: All had been diagnosed with radiology-confirmed supratentorial ischemic stroke, had been treated within 24 to 72 hours, had NIH Stroke Scale (NIHSS) scores of 3 to 21, and had impaired gait.
But the researchers found that 90 days after the stroke, the median Rankin Score was not significantly different between patients who were treated with the investigative compound GSK249320 or placebo; in addition, no significant differences were found for the 90-day NIHSS score, reported Steven C. Cramer, MD, professor of neurology at the University of California, Irvine.
Researchers were hopeful that the phase 2b trial would be able to build on pre-clinical studies, human safety studies, and a small phase 2 study that indicated there was an improvement in gait velocity. The trial was halted early for futility, however, at the first pre-specified interim analysis.
The report, which was also published online Wednesday in the journal Stroke, noted that GSK249320 did what researchers had anticipated: It slowly reduced the levels of MAG, a substance that appears to inhibit the myelin-based protective effect on nerves. But that reduction failed to have an impact on improving the gait of the patients who had strokes.
"GSK249320, administered intravenously and initiated within 72 hours of stroke onset, demonstrated no improvement on gait velocity compared with placebo," Dr. Cramer said. He noted, however, that the agent was well-tolerated and showed low immunogenicity — "findings [that may be] potentially useful to future studies."
Among the issues that may have contributed to the failed trial, he said, were that the endpoint of gait improvement had too large of a floor effect at baseline — more than 80 percent of the stroke patients were unable to ambulate at all at baseline, the enrolled patients had severe levels of defect, and the antibody dose was too low. Dr. Cramer concluded that it may be that GSK249320 just does not work in human stroke.
Commenting on the study, Daniel T. Lackland, PhD, professor of epidemiology and neurology at the Medical University of South Carolina in Charleston, said: "We have seen a number of purported neuroprotective agents that have failed, and while this is another such study, it is still a goal that must stay on the table."
"This is much too important an issue to give up," said Dr. Lackland, who was not involved with the study. "We have been trying to find an agent for a long time, but we haven't gotten there yet."
The trial was sponsored by GlaxoSmithKline.
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