Canada-based Clementia Pharmaceuticals has started a double-blind, placebo-controlled Phase II clinical trial of palovarotene to treat fibrodysplasia ossificans progressiva (FOP), a rare, severely disabling genetic disease.
FOP is characterised by painful, recurrent episodes of soft tissue swelling (flare-ups) and abnormal bone formation in muscles, tendons and ligaments.
The company said that the new, abnormal bone formation, or heterotopic ossification (HO), causes morbidities and progressive disability.
International Fibrodysplasia Ossificans Progressiva Association (IFOPA) president and founder Jeannie Peeper said: "Over the last several decades, the IFOPA has been focused on connecting families and researchers in the search for a cure.
"With this announcement, the work of the entire FOP community advances out of the realm of basic research and into the first of what we hope will be many controlled clinical trials, the next step in the ultimate goal of finding a successful treatment for FOP."
The Phase II trial is designed to assess the effect of different doses of palovarotene on new bone formation during and after a flare-up in 24 patients with FOP who aged 15 or older.
The company said that treatment will be started within seven days from flare-up onset and continue for six weeks with an additional six weeks of follow-up.
In the trial, a number of clinical endpoints will assess the efficacy and safety of palovarotene, including imaging endpoints for new bone formation and clinical assessments of physical function and patient-reported outcomes.
University of Pennsylvania School of Medicine molecular orthopedic medicine division chief and trial principal investigator Frederick Kaplan said: "Ever since we first identified the mutation responsible for FOP, work has expanded throughout the world to find molecules that could block this target and one day lead to clinical trials.
"Palovarotene, a retinoic acid receptor gamma agonist that appears to potently inhibit endochondral bone formation in animal models, is the first to enter well-controlled clinical trials."
The company said that palovarotene prevented heterotopic bone formation in mouse models of FOP and this Phase II trial is designed to determine whether the effects seen in these mouse models could be recapitulated in patients with FOP.
The trial to be carried out at three investigational sites is expected to be completed during 2015.
The sites include the University of Pennsylvania, the University of California and the Hôpital Necker Enfants Malades in Paris.
Image: The effects of Fibrodysplasia ossificans progressiva, a disease which causes damaged soft tissue to regrow as bone. Photo: courtesy of Joh-co.