Dr. Teresa Gidaro is the principal investigator for France in the multicentre, WAVE trial that launched in June at I-Motion. This phase I international trial also includes sites from the United Kingdom, the United States and Belgium, where Laurent Servais is the principal investigator at his site in Liège.
What is the new molecule investigated in this trial?
WVE-210201 * is an antisense oligonucleotide capable of skipping exon 51 of the DMD gene coding for dystrophin, in order to produce a shorter but functional dystrophin. This new molecule adds to other products aimed at skipping exon 51 and tested in Duchenne muscular dystrophy: Biomarin’s drisapersen, Sarepta’s eteplirsen.
How will the study proceed?
The purpose of this double-blind, placebo-controlled study is to evaluate the safety, tolerability and pharmacokinetic profile of WVE-210201. The molecule will be administered intravenously in 40 non-ambulatory boys, aged 5-18 years with Duchenne muscular dystrophy (DMD) and amenable to exon 51 skipping. The study includes 5 cohorts of patients who will test 5 increasing doses of WVE-210201.
The study must take place in two phases. Initially, each participant will receive a single dose of treatment or placebo. For each cohort, 6 patients will receive the product and 2 patients will receive the placebo.
Since this is the first time that this product will be injected into humans, for each cohort there will be 2 “sentinel” patients, injected one after the other. If everything goes well after 48 hours, the other 6 patients in the cohort will in turn receive an injection within 24 hours. After injection, a complete clinical follow-up is carried out: clinical examination, follow-up of adverse events and biological samples will be collected on the day of treatment (day 1), then every week for 4 weeks, and every month during 2 months, until the 85th day after administration.
Once this first phase has been completed, what are the next steps?
The study then goes into the open phase: all patients who participated in the previous phase will receive injections of WVE-210201 every week for 4 months. At this stage, we are not looking for a clinical effect, we are just validating the proof-of-concept (i.e. this molecule allows the synthesis of a truncated but functional dystrophin) therefore the follow-up will focus on muscle and the potential effects of the injected product: muscle biopsy samples will be obtained and compared to biopsies obtained prior to injection.
At which phase are you at I-Motion?
Like the other centres, we are at the beginning of the first phase: single injection and clinical follow-up over 2 months. Our first cohort of 3 patients was treated with 1 mg between June and August, and injections of the 2 patients included in the second cohort have just been completed. The second cohort is already complete for all centres, and we now await the results. If all goes well and there are no adverse events, we will be able to start including patients in the 3rd cohort, theoretically around November 2018.
*This molecule was developed by Wave Life Sciences Ltd, an American company.
> For more details of this trial « Safety and Tolerability of WVE-210201 in Patients With Duchenne Muscular Dystrophy »
