Ceftriaxone, an intravenous (IV) administered antibiotic ordinarily used for lung, brain and urinary tract infection that exhibits strong neuroprotective properties in addition to its anti-bacterial effects, underwent a clinical trial to determine its efficacy as a treatment for ALS patients from 2006 to 2012. Laboratory studies of Ceftriaxone showed demonstrable motor neuron protection from different types of injury, and the drug showed promise in human cell cultures and rodent models. Although hopes were high, on August 8, 2022, the National Institute of Neurological Disorders and Stroke (NINDS) announced that the Phase III trial would be discontinued 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, director ofthe MDA/ALS Center at Massachusetts General Hospital in Boston. In a statement issued on the same date 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 has not yet been released.
Statement on the Clinical Trial of Ceftriaxone from the ALSA:
In July 2012, the DSMB for the NINDS-sponsored clinical trial of ceftriaxone in ALS recommended that based on existing data the trial be stopped because the study was unlikely to reach the pre-determined efficacy criteria. The NINDS leadership concurred. Pre-clinical research identified ceftriaxone as a promising treatment for ALS therefore it was important for people with ALS to find out if the drug could be beneficial in ameliorating the disease. The study used a novel seamless adaptive design. Final analysis and presentation of the results will occur after completion of site monitoring and database lock. The important contributions of patients, their families and the hard work of the investigators and their teams made it possible to implement the trial. While all had hoped for a more positive result, the trial has moved ALS research forward.
The Northeast ALS Consortium
Ceftriaxone- Identifier Number NCT00349622*
This clinical trial is in Phase III testing. It is a double-blind, randomized, placebo-controlled, multi-center study trial, which means the participant may or may not receive the actual medication. Safety has already been established in Phase I and Phase II. Results of efficacy in this Phase III are based upon the ALSFRS-R score. The medication requires a Hickman catheter through which intravenous infusions are given twice daily by the patient or caregiver. This trial will continue until the last patient is enrolled, plus 12 months.
More information about the trial and about Ceftriaxone can be read at the ALS/MDA News Magazine.