New Oral Drug in Phase 1 Safe to Treat Spinal Cord Injury

New research from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London has demonstrated the safety and tolerability of a new drug treatment designed as a therapeutic intervention for spinal cord injury (SCI). 

The research, published in the British Journal of Clinical Pharmacology, found that the KCL-286 drug—which works by activating retinoic acid receptor β (RARβ) in the spine to promote recovery—was well tolerated by participants in a Phase 1 clinical trial, with no severe side effects. Researchers are now seeking funding for a Phase 2a trial studying the safety and tolerability of the drug in those with SCI. 

The global prevalence of SCI is estimated to be between 0.7 and 1.2 million cases per year, with falls and road accidents being the major causes. Despite incurring a cost of $4 billion per year in direct healthcare and indirect costs (i.e., inability to work and social care) in the US alone, there are no licensed drugs that can tackle the intrinsic failure of the adult central nervous system to regenerate and, thus, remains a largely unmet clinical need.

Previous research by various groups has shown that nerve growth can be stimulated by activating the RARβ2 receptor, but no drug suitable for humans has been developed. KCL-286, an RARβ2-agonist, was developed by Jonathan Corcoran, PhD, professor of neuroscience and director of the Neuroscience Drug Discovery Unit, at King’s IoPPN, and team, and used in a first-in-man study to test its safety in humans. 

The SAD and MAD trials

109 healthy males were divided into one of two trial groups: single ascending dose (SAD) adaptive design with a food interaction (FI) arm and multiple ascending dose (MAD) arm. Participants in each arm were further divided into different dose treatments.   

SAD studies are designed to establish the safe dosage range of a drug by providing participants with small doses before gradually increasing the dose provided. Researchers look for any side effects and measure how the drug is processed within the body. MAD studies explore how the body interacts with repeated administration of the drug, and investigate its potential to accumulate within the body. 

Researchers found that participants could safely take 100 mg doses of KCL-286, with no severe adverse events. “This represents an important first step in demonstrating the viability of KCL-286 in treating spinal cord injuries. This first-in-human study has shown that a 100 mg dose delivered via a pill can be safely taken by humans. Furthermore, we have also shown evidence that it engages with the correct receptor,” Corcoran, the study’s senior author said. “Our focus can hopefully now turn to researching the effects of this intervention in people with spinal cord injuries.” 

- This press release was originally published on the King’s College London website