Addex Therapeutics announced that the company will conduct a phase IIa Proof of Concept Study of dipraglurant in focal cervical dystonia (CD). Addex expects to initiate the trial in the fourth quarter of 2016. The study was developed with support from the Dystonia Medical Research Foundation and in collaboration with investigators from the Dystonia Coalition, an international network of experts devoted to advancing research in dystonia. Buz Jinnah, Director of the Dystonia Coalition and Professor of Neurology at Emory University, will serve as the lead investigator.
Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. Dystonia represents the third most common movement disorder in humans and comprises a large number of clinical syndromes.
Addex’s phase IIa Proof of Concept study will include 18 focal CD patients who are currently sub-optimally treated with BoNT. The single center study will be double-blinded and placebo-controlled. A single dose of dipraglurant will be administered in a crossover design. The TWSTR scale, a well-established clinical rating scale designed to detect drug induced changes, will serve as the primary endpoint of the trial. Key secondary endpoints will include an evaluation of the Cervical Dystonia Impact Profile, a patient-reported outcome for quality of life, pharmacokinetics and safety and tolerability.
“Cervical dystonia is a rare disorder that is not easy for most doctors to treat. BoNT provides partial relief for many patients, but it has its limitations - we need to do better,” said Professor Jinnah. “An oral medication would be a great option, and dipraglurant is the first oral agent brought forward for this condition in decades. We are delighted to be able to test it for our patients."
“Dipraglurant has demonstrated robust efficacy in a phase II study in patients suffering from levodopa-induced dyskinesia associated with Parkinson’s disease which included patients suffering from dystonia,” said Sonia Poli, CSO of Addex. “This clinical data in Parkinson’s disease patients and preclinical data in multiple models of dystonia is highly supportive of studying dipraglurant in focal cervical dystonia.”
Dipraglurant is an oral, small molecule allosteric modulator that inhibits selectively the metabotropic glutamate receptor 5 (mGluR5), a Class C G¬-Protein Coupled Receptor, with potential to be used in combination with levodopa or dopamine agonists or as a standalone treatment for Parkinson's disease levodopa ¬induced dyskinesia (PD¬LID), motor and non¬motor symptoms of Parkinson's disease and other movement disorders. In a double-¬blind, placebo-¬controlled, US and European phase II study in PD¬LID, data showed that dipraglurant met the primary objective of the study by exhibiting a good safety and tolerability profile. Dipraglurant also demonstrated a statistically significant reduction in LID severity with both 50 and 100 mg doses. Dipraglurant reduced dystonia severity in addition to chorea, the two major LID components. Efficacy was measured using the modified Abnormal Involuntary Movement Scale and patient diaries documenting "off¬-time" (impaired voluntary movement), "on-¬time" (with or without dyskinesia) and sleep. Additional endpoints include the Unified Parkinson's Disease Rating Scale, the Clinical and Patient Global Impression of Changes scales, and an evaluation of the patient’s mood using the Hospital Anxiety and Depression Scale. The trial was supported by a grant from The Michael J. Fox Foundation for Parkinson's Research.
