Clinical Trial Ceftriaxone in Subjects With ALS

It is known that nerve cells called motor neurons die in the brains and spinal cords of
people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is
unknown. Researchers think that increased levels of a chemical called "glutamate" may be
related to the cell death. For this reason researchers want to study drugs that decrease
glutamate levels near nerves. Ceftriaxone—a semi-synthetic, third generation cephalosporin
antibiotic—may increase the level of a protein that decreases glutamate levels near nerves.
Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from
injury.

Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating
bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to
people over a long period of time, such as months or years. The goals of this study are to
evaluate the safety and effectiveness of ceftriaxone as a treatment for ALS, and to
determine the safety and effectiveness of long-term use of the drug in people with ALS.

A total of 600 eligible people with ALS will be enrolled in this multi-center research
study. Participants will be randomly assigned to receive treatment with ceftriaxone (2/3 of
participants) or placebo (1/3 of participants) for at least 12 months.

The study consists of three stages. The first stage, which has completed enrollment, will
look at whether ceftriaxone enters the cerebrospinal fluid (the fluid that surrounds the
spinal cord, also called CSF) in amounts that are high enough to be of possible benefit.
The second stage, which has also completed enrollment, will look at the safety and side
effects of the study drug when taken daily for at least 20 weeks. The study is currently
enrolling subjects for the third stage, which began in Spring 2009, and will determine
whether the study drug prolongs survival and slows decline in function due to ALS.