The proof-of-concept study (NCT03575676) will recruit participants in four clinical sites in or near Barcelona, Spain. It is expected to include about 30 patients with a genetically confirmed diagnosis of Huntington’s disease.
“We are very proud to start this clinical trial of SOM3355 in Huntington patients,” Raúl Insa, MD, PhD, founder and CEO of SOM Biotech, said in a press release. “The four hospitals taking part in the trial are of excellent profile and we are confident that the recruitment will go smoothly.”
Eligible participants must be able to walk independently and their chorea scores must be of 8 or higher, as determined by the Total Maximal Chorea score of the Unified Huntington’s Disease Rating Scale (UHDRS). Chorea is characterized by brief and abrupt movements that are irregular and unpredictable.
The study will have a duration of 27 weeks and will have two groups of patients to evaluate the safety and effectiveness of SOM3355. During the study, patients will receive either a placebo or twice-daily SOM3355 — 100 mg or 200 mg doses — for six-week periods.
The study’s main objective is to measure changes in uncontrolled chorea movements from baseline. But researchers also will assess other disease domains, including impression of change, function capacity, gait, overall movement, and safety.
Treatment-related adverse events also will be studied, with particular focus on blood pressure and cardiovascular events.
“Currently, the treatment of movement disorders in Huntington’s disease is limited by the side effects of the drugs used. SOM3355 offers a promising alternative to improve the tools available to treat the disease,” said Jaume Kulisevsky, MD, PhD, principal investigator of the study at the Hospital de la Santa Creu i Sant Pau in Barcelona. “The clinical trial that we begin has a double-blind and randomized design that will allow to verify objectively the ability of the drug to improve abnormal movements.”
SOM3355 is an inhibitor of the β1‐adrenoceptor, designed to act on heart cells and treat high blood pressure and other heart conditions. It was discovered first in the U.S. and is approved in several countries in Europe and Asia.
But studies revealed that SOM3355 also is a potent inhibitor of the VMAT2 protein, which is an important modulator of dopamine levels. Because dopamine is key for normal, coordinated movements, the medicine could represent a potential therapeutic option for treating choreic movements in Huntington’s.
Preclinical data has demonstrated that SOM3355 improves movement control while reducing side effects often caused by other VMAT2 inhibitors.