Combination of Celecoxib/Ciprofloxacin Safe and Tolerable for Amyotrophic Lateral Sclerosis
In the open-label PARADIGM trial, 15 participants with amyotrophic lateral sclerosis (ALS) were treated with celecoxib/ciprofloxacin therapy (PrimeC; NeuroSense Therapeutics, Herzliya, Israel) for 12 months. The treatment was safe and had a statistically significant impact on TDP-43 and other ALS-related biomarkers. Safety was assessed as participants’ survival compared with predicted survival rates.
Based on these results, the phase 2b PARADIGM trial (NCT05357950) will enroll 69 participants, who will be randomly assigned 2:1 to receive the celecoxib/ciprofloxacin combination or placebo. This trial will assess ALS biomarkers, clinical efficacy, and improvement in quality of life.
"This clinical study is a very important achievement and milestone for the ALS community. It is very encouraging to see that there was both biological activity and clinical signals of a treatment effect," said Vivian Drory, MD, director of the Neuromuscular Diseases Unit at Tel Aviv Sourasky Medical Center and principal investigator of the study. "I am thankful to all participants, their families, and staff who took part in this study, and proud and excited to participate in the PARADIGM study, which utilizes an upgraded formulation of PrimeC."
"This study, as well as previously published preclinical work, provides strong encouragement for the continued development of Prime C. We need more treatments for ALS, and PrimeC is an exciting candidate," stated Jeremy M. Shefner, MD, PhD, FAAN, professor of Neurology, chief medical officer for Clinical Research, at Barrow Neurological Institute, and coauthor of the paper.
Dr. Erez Eitan, coauthor of the study and chief scientific officer of NeuroDex, stated, "We are proud to work with NeuroSense's team on the implementation of ExoSORT, our proprietary method for isolating neuron-derived exosomes from blood samples for identification and measurement of biomarkers. When we discovered that TDP43, a major ALS biomarker, and LC3, an autophagy biomarker, can be measured in NDEs and are different in ALS patients, we hoped this would help to advance therapeutic development. We are thankful to NeuroSense for providing us with the opportunity to test the biomarkers in their clinical trials." NeuroDex is advancing brain diagnostics through its proprietary cell-specific exosome diagnostic platform providing a noninvasive, inexpensive, and robust diagnostic tool.
Adverse events (AEs) were seen in 4 participants; none of these AEs were unexpected, and most were mild or moderate (69%). No serious AEs were related to the study drug. Only 1 participant tested positive for COVID-19 and recovered without complications, and no other abnormal laboratory investigations were found.