An open label phase I/IIa trial repurposing carbamazepine (CBZ) for the treatment of skeletal dysplasia in children.
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Duration of Study in the UK
4 years, 0 months, 30 days
The aim of the MCDS therapy study is to evaluate the effect of carbamazepine on children with a diagnosis of Metaphyseal Chrondrodysplasia Schmid Type (MCDS) with confirmed COL10A1 pathogenic mutation. There is currently no specific treatment for patients with MCDS, and patient care is based only on the management of symptoms.
The study is based on the results of preclinical studies, which support the efficacy of carbamazepine on cells and on mice with a COL10A1 mutation, both at a molecular level on the pathogenic mechanism reducing ER stress, and on growth and bone alignment in mice.
Carbamazepine (CBZ) is a well-established drug, which has been widely marketed throughout Europe since the 1960s and is routinely used in paediatric care for the treatment of epilepsy and neuropathic pain. It has a well-known safety profile. There is no clinical reason to expect a different safety profile of CBZ in patients with MCDS compared to patients of similar ages treated with CBZ for epilepsy. Its effects on patients with MCDS have never been investigated.
The study involves children with MCDS, as to evaluate the effect of CBZ on growth and bone alignment it is necessary to evaluate this on patients who have not reached bone maturity. The study aims to recruit 40 patients
This is a multicentre international clinical trial. All clinical centres are regional or national referral centres for the diagnosis and management of patients with Genetic Skeletal Diseases including MCDS.
The two-stage study will last a total of 60 months and will be comprised of an initial dose determination stage in a cohort of 12 patients (12 months)followed by long-term assessment of efficacy and safety at the chosen dose in a cohort of 28 patients (24 months).
Yorkshire & The Humber - Sheffield Research Ethics Committee
Date of REC Opinion
19 Nov 2018