Phase 3 Trial of Ceftriaxone in ALS Stopped

On Aug. 8, 2012, the National Institute of Neurological Disorders and Stroke (NINDS) reported that it has stopped a phase 3 clinical trial of the antibiotic ceftriaxone in amyotrophic lateral sclerosis (ALS) because the study was "unlikely to reach the predetermined efficacy criteria."

NINDS (part of the National Institutes of Health) sponsored the trial, which was led by neurologist Merit Cudkowicz, who directs the MDA/ALS Center at Massachusetts General Hospital in Boston.   

In a statement issued Aug. 8, 2012, by the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS), it was noted that the recommendation to stop the trial was made in July 2012 by the trial's Data and Safety Monitoring Board (DSMB), a group of experts who monitor efficacy data and the safety of trial participants during the course of a trial. (NEALS is an international group of researchers who collaboratively conduct clinical research in ALS and other motor neuron diseases.)

Final analysis will be presented at a later date.

About the trial

The ceftriaxone clinical trial was conducted at 60 study sites in the United States and Canada. Trial participants received an intravenous catheter, inserted in the chest. A small opening on the catheter was used to administer either ceftriaxone or placebo.

Trial participants were randomly assigned to either the ceftriaxone (treatment) group, or the placebo (control) group, and the trial was double-blinded, meaning neither trial participants nor investigators knew which substance each participant was receiving.

Primary measurements for determining efficacy were survival time and symptom progression as measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), a validated ratings scale used by physicians to assess symptom progression in people with ALS.

About ceftriaxone

Ceftriaxone is an antibiotic approved by the U.S. Food and Drug Administration (FDA) to treat a range of illnesses including bacterial meningitis, mild to moderate pneumonia and Lyme disease.

It was identified as a potential drug candidate for ALS in an NIH-sponsored drug screen nearly a decade ago. In numerous studies that followed, it was demonstrated that ceftriaxone increases survival in human central nervous system cell cultures, rat spinal cord cultures and rodent research models of ALS.

Ceftriaxone was thought to work in ALS by decreasing toxic levels of a chemical called glutamate near motor neurons.

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