Protocol – questions and answers

15th February 2013

Q. If a subject recently had an investigation which is part of screening procedures (e.g. Echocardiogram), does it need to be repeated?

A: This will depend on the investigation (e.g. blood tests must be performed at screening), the time window since the investigation and technique. Please contact the Chief Medical Coordinator (Dr Michela Guglieri, contact details in section 2.1 of the MOO) to discuss the specific circumstance.

Q: Does the order in which we perform the tests matter? 

A: At screening we would recommend checking the reliability of the FVC and the ability to take tablets first as these are inclusion criteria. If the boy does not pass these inclusion criteria, the family can be provided with placebo tablets and FVC filters/tubes to practice at home and re-screening  should be considered. However if the boy is not able to provide reliable FVC measures and/or to swallow tablets, sites can consider not proceeding to the other screening procedures on that day.  Physio assessments have a specific order in which the tests should be performed (see Clinical Evaluator Manual, section 3, page 9). This applies at screening and at each follow up visit. Otherwise, the other study procedures can be performed in the order that it is most convenient for the subject and/or study staff.

Q: Can tablets be swallowed with yogurt or any other liquid/food?

A: Yes. As previously discussed, we are aware that the ability to swallow tablets will be one of the major difficulties for young children.  As per common recommendation from medicines for children,  tablets should be swallowed with a glass of water, milk or juice. Alternatively, they can be concealed  in a small amount of soft food such as yogurt, applesauce, honey or jam.  If tablets are to be concealed in this way, we suggest that you discuss with parents what the child would manage best, and whether it would be better for the child to see the tablets before concealment. Tablets should not be chewed or crushed.

Q: Do we only do the second FVC at the screen visit?

A: Yes, The FVC re-test needs to be done at screening day one only to confirm eligibility

Q: Can the subject’s medical and medication history be collected from the subject’s medical notes?

A:  Yes. However it is important that the information are confirmed with the family at the study visit. Please note also that CRFs should not be pre-filled with subject information until the informed consent form (and assent if required) is signed.

Q: Can blood samples for bone-metabolites and for bio-banking be collected at screening together with the other blood samples?

A: We are aware that blood sample collection might be stressful for young children. As per protocol blood samples for bone-biomarkers and for biobanking have to be collected at baseline. Collection of these samples at screening would represent a deviation from the protocol and would therefore require the site Investigator to complete a deviation form (eCRF80 see section 6.6 of the MOO, page 48). However please note that in line with GCP and paediatric guidelines in research, you  are not allowed to collect more than 1-1.5 ml/kg within 24 hours for research studies in paediatric population.

The urine sample for bone-DMD needs to be collected at baseline as families will need to be instructed to collect the 2 hour morning sample (see MO, section page 61 for details) and no study procedures can be performed before consent.

Q: How involved is the eye exam?  Can the site investigator do this or should we schedule an eye appointment?

A: The eye check needs to be performed by an ophthalmologist or a qualified eye care practitioner (see section 6.13 of the MOO)

Q: Will the DEXA scan be centrally read and will sites receive DEXA scan result reports?

A: No, the DEXA scan will be sent centrally (ML Bianchi) for quality control only. The DEXA scan will therefore need to be interpretered locally and interventions should be arranged as per local clinical guidelines (see MOO, section 6.14.4, page 66).

Q: What is the wrist X-Ray for?

A: The wrist X-Ray is being performed for bone age calculation. This might not be a standard procedure at the radiology department; therefore please ensure that “wrist X-Ray for BONE AGE” is specified on the requisition form.