12. What happens if I’m in the placebo group?
The MO‐Ped Trial has three treatment groups.
Two groups will receive one of two daily dosages of palovarotene and the third group will receive placebo. However, because treatment is “blinded,” no one knows who is assigned to which group, including the subject, caregivers, study physician and study site personnel and Clementia. All other procedures and assessments remain the same for all subjects. At study enrollment, subjects will go through a randomization process (like flipping a coin) that determines which treatment they will receive. This process ensures an equal number of subjects are assigned across the three groups. The chance is one out of three that a subject would be assigned to the placebo group, and two out of three for assignment to a palovarotene group. When the subject completes participation in the MO‐Ped Trial, the subject may be eligible for an open label extension study. All subjects from the MOPed Trial including those who had
received placebo will receive palovarotene in the extension trial.
13. Will subjects in the MO‐Ped Trial be able to receive their usual care? Yes. Subjects will receive their usual standard of care treatments for Multiple Osteochondroma (MO). For example, the study physician
may administer pain medication, or undergo surgery to remove a painful osteochondroma, or to correct a deformity or a functional limitation in the movement of a joint. However, some medicines are not permitted during the MOPed trial because they may interfere with palovarotene. These are not frequently used medicines and usually, a substitute can be used. Clinical study personnel will discuss this information with you during the study screening process.
14. Are MO‐related surgeries allowed during participation in the MO‐Ped Trial? Yes, surgeries for the treatment of Multiple Osteochondromas (MO) are part of the standard of care and therefore are allowed during the MO‐Ped Trial
15. What if a subject enrolled in the MO‐Ped Trial experiences side effects due to the treatment? Side effects are monitored throughout the MO‐Ped Trial. Any subject who experiences a side effect during the MO Ped Trial will be evaluated by the study physician and study site staff and treated appropriately. As a part of the management of side
effects, the study physician may instruct a subject to decrease the frequency of dosing or stop treatment (either
temporarily or permanently). All subjects have the option to stop their participation in the MO-Ped Trial at any time without
affecting any treatments they would normally receive. Known potential side effects will be described in the informed consent form. This
form is a detailed document that the study physician and/or study staff will discuss thoroughly with potential subjects during
the enrollment evaluation. The evaluation process gives potential subjects an opportunity to ask any questions regarding the MO‐Ped Trial, including questions about the potential health risks and safety monitoring.
16. Why do you do MRI and what does that mean for my child? Magnetic resonance imaging (MRI) is the best way to image the structure and size of osteochondromas and to visualize the relationship of osteochondromas to the normal skeleton. Using MRI, we can count the number of osteochondromas in the body and measure the total volume of these osteochondromas. This is one of the measures to assess palovarotene’s potential effects on
osteochondroma growth. Whole body MRIs will be performed at the first study visit, every 12 months during the study, and at early
conclusion for subjects who discontinue the study prior to its completion.
MRI uses a large magnet to visualize the body parts; so, there is no radiation, it is not painful but it does take a long time and makes loud
noises. Your child will need to lie still on a bed that slides into the MRI tube for about 1 hour to obtain good images. This may be hard for some young children and they may need sedation so they can be calm or sleep through the process.
17. Why do you perform X‐rays in addition to the MRI?
X‐ray images (called radiographs) are necessary to evaluate whether the bones in the arms and legs are growing normally. The joints and
limbs may become deformed in the presence of an osteochondroma. The legs may also be of different lengths. By taking X‐rays
at baseline and every 12 months, we can evaluate new or worsening deformities in the arms and legs.
It is also important to monitor the effect that palovarotene may have on growth plates throughout the MO-Ped Trial. Therefore,
all study subjects will have X‐rays of one knee and one hand/wrist at study screening and every 6 months during the 24‐month
treatment period to monitor for both linear growth and any growth plate changes. Once the growth plates are completely closed at a body site, follow‐up X‐rays for that body part are no longer required.
Dual –X-ray absorptiometry (DXA) scans of the spine, one hip, and one radius will be performed at baseline and every 6 months
to monitor bone thickness as part of safety monitoring.