Subjects must also have symptomatic MO, which is defined as any of the following:
A new or enlarged osteochondroma that occurred in the preceding 12 months.
A painful osteochondroma, skeletal deformity, or a limitation in joint movement.
A prior surgery for an MO‐related complication.
Additional inclusion and exclusion criteria are available at www.clinicaltrials.gov. Subjects must also comply with study visits and assessments to qualify and these will be explained to you by the study physician.
4. What is the purpose of MO‐Ped Trial and what are the clinical endpoints?
The purpose of the MO Ped Trial is to evaluate the efficacy and safety of two palovarotene dosage regimens on MO patients and to determine whether treatment with palovarotene over 24 months can reduce new osteochondroma formation, the volume of osteochondromas, new or worsening of limb deformities, or MO‐related surgeries.
5. What is palovarotene?
Palovarotene is an investigational medicinal product belonging to a group of compounds called retinoids. It is specifically classified as a selective retinoic acid receptor gamma agonist (RARγ). Clementia is developing palovarotene as an orally administered treatment for patients with Multiple Osteochondromas (MO) and for another rare bone disease known as fibrodysplasia ossificans progressiva (FOP).
Palovarotene has been studied in over 800 humans, including healthy volunteers, people with COPD, and individuals with FOP. Safety
information has been gathered from pediatric patients with FOP. Side effects involve the skin and mucous membranes (e.g., lining inside of your nose and mouth) and not other organs in the body. Specifically, side effects of dry skin, dry lips, itching, rash, redness, mouth sores, and
hair loss are seen. In general, the number, severity, and duration of these mucocutaneous and dermatologic side effects increased as the palovarotene dose increased. Most of these were mild or moderate in severity and generally resolved or improved after treatment with skin lubricants, lip balms, antihistamines, or by decreasing the dose of palovarotene if necessary.
Effect on bones and skeletal growth are especially important for pediatric subjects. In juvenile animals administered palovarotene, minor
shortening of the limb bones has been observed particularly in younger animals and at high doses. At doses to be used in the MOPed trial, any potential abnormalities observed are predicted to be mild and at least partiallyreversible after the treatment is stopped. In the FOP studies,
growth plates and linear heights were examined in children who are still growing and received episodic high dose treatment during flares.
Appropriate increases in bone age, linear and knee height were observed in most subjects. No premature closure of the growth plate was notedin any subject. In the MO‐Ped trial, safety monitoring for bone effects and growth will occur to identify any potential adverse growth effects.
6. How will the treatment be administered?
Palovarotene is a once a day pill. Specifically, powder-filled gelatin capsules are preferably taken following the first meal of the day.
Absorption of the medicine is better with a full meal. For younger children who may have difficulties swallowing intact capsules, parents may sprinkle the contents of the capsule onto a teaspoon of food (such as pudding, yogurt), so that the entire dose can be taken.
7. How is the dosing determined for palovarotene for children?
The dosages of palovarotene to be tested in MOPed Trial are chosen to maximize the inhibition of osteochondroma growth and to minimize risk of adverse effects. These doses are based on the Multiple Osteochondromas (MO) animal data on efficacy and safety, preliminary
pharmacokinetic data from subjects with Fibrodysplasia Ossificans Progressive (FOP), as well as clinical safety data from subjects with Chronic Obstructive PulmonaryDisease (COPD) and FOP. The doses to be tested are 2.5 and 5 mg once daily and are adjusted by
weight so that the amount in the blood is in the range that is targeted for the desired drug effects and to minimize potential adverse effects.