Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne, vamorolone, santhera, long-term safety
Brief summary
This study aims to assess safety and effectivness of long-term treatment with vamorolone in boys with Duchenne Muscular Dystrophy (DMD) who have completed prior studies with vamorolone.
Detailed description
All subjects in this study have completed previous studies with vamorolone and continued to receive vamorolone under special programs: Compassionate Use Program \[CUP\], Named Patient Program \[NPP\] or Expanded Access Protocol \[EAP\]. All subjects will continue treatment with vamorolone under Guardian protocol instead. The primary objective of this study is to evaluate the safety of long-term treatment with vamorolone in boys with Duchenne Muscular Dystrophy regarding vertebral fractures. Secondary study objectives will evaluate the safety of long-term treatment with vamorolone on non-vertebral fractures, cataracts, delayed puberty, overall safety as well as ambulatory and non-ambulatory function.
Interventions
DRUGvamorolone 40 mg/mL oral suspension
Vamorolone is administered at a dose range between 2 mg/kg/day and 6 mg/kg/day for boys weighing \<40 kg. For boys weighing 40 kg or above, the dose range will be 80 mg to 240 mg once daily. Doses can be adjusted within the dose range as determined by the Investigator based on tolerability. The highest tolerated dose should be used.
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Healthy volunteers
No
Inclusion criteria
* Subject and/or subject's parent(s) or legal guardian has provided written informed consent * Subject has previously completed either the VBP15-LTE or VBP15-004 study, and transitioned through the Compassionate Use Program, Named Patient Program or Expanded Acess Protocol * Subject is on vamorolone on day of enrolment * Subject and parent / legal guardian are willing and able to comply with the protocol schedule, assessments and requirements
Exclusion criteria
* Any medical condition, which in the opinion of the Investigator, would affect study participation, performance or interpretation of study assessments * Vamorolone treatment discontinued for ≥ 6 months within the year prior to enrolment for a non-safety reason, or vamorolone treatment previously discontinued at any time for a safety reason * Severe hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of vertebral fractures per 1000 person-years based on X-ray central reading. | At Enrolment and every 2 years during a Full visit | Lateral thoracolumbar spine X-Rays will be collected and sent to a central reader for evaluation of vertebral fractures |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first vertebral fractures (cumulative incidence) | From enrolment up to at least 2 years | — |
| Number of non-vertebral fractures per 1000 person-years based on investigator reporting | From enrolment until up to at least 3 years | Non-vertebral fractures will be reported by investigators and not reviewed centrally |
| Time to first non-vertebral fractures (cumulative incidence) | From enrolment until up to at least 3 years | — |
| Number of cataracts per 1000 person-years based on ophthalmologist assessment | From enrolment until up to at least 3 years | An ophthalmologist assessment including assessment of posterior capsular cataracts by slit lamp will be performed yearly |
| Number of subjects not reaching Tanner stage 2 by 15 years of age | From enrolment until up to at least 3 years | Qualified personnel (eg, an individual, part of the endocrinology team and trained to assess Tanner stages) will provide an assessment of the puberty status of the subject, including testicular volume. |
| Frequency of adverse events (AEs) and serious adverse events (SAEs) | From enrolment until up to at least 3 years | The occurrence of AEs should be sought by questioning of the subject and/or his caregiver at each visit or phone call during the study. All SAEs occurring from signature of the ICF up to 30 days after last dose of study medication must be reported, irrespective of severity or whether or not considered related to study medication. All SAEs must be reported within 24 hours of becoming aware of the event, whether or not the SAE is considered to be related to the study medication. |
| Change from baseline in body weight | From enrolment until up to at least 3 years | Physical examination will include weight (in kg) |
| Number of subjects with clinically relevant laboratory abnormalities | From enrolment until up to at least 3 years | Clinically relevant laboratory abnormalities will include HbA1c and morning cortisol measurements. |
| Change from baseline in Time to Stand (TTSTAND) velocity | From enrolment until up to at least 3 years | The TTSTAND measures the time (in seconds) required for the subject to stand to an erect position from a supine position (floor) |
| Six-minute Walk Test (6MWT) | From enrolment until up to at least 3 years | 6MWT will be performed only in the ambulatory subjects. The total distance traveled, in meters, should be recorded along with the validity of the test as assessed by the test administrator. If a subject cannot complete 6 minutes of walking, the total meters and the time until discontinuation of the test should be recorded. |
| Change from baseline in 6MWT distance | From enrolment until up to at least 3 years | — |
| Age at ambulatory and non-ambulatory milestones | From enrolment until up to at least 3 years | Ambulatory milestones include Loss of standing from the floor, Loss of ability to climb 4-stairs, Loss of ability to walk 10 meters (loss of ambulation), Loss of ability to stand unassisted. Non-ambulatory milestones include Loss of ability to perform hand-to-mouth function, Loss of ability to use a manual wheelchair, Loss of ability to transfer independently from wheelchair, Nocturnal ventilation and Full time ventilation. |
| North Star Ambulatory Assessment (NSAA) scores | At enrolment and each Full visit (Month 12, 24, 36, etc / End-of -Treatment) until End of Study | The NSAA is a 17-item rating scale that is used to measure functional motor abilities in ambulant children with DMD and allows to monitor the progression of the disease and treatment effects. |
| Change from baseline in body height | From enrolment until up to at least 3 years | Physical examination will include height (in cm). Ulnar length of the non-dominant arm will be used if standing height cannot be measured. |
| Change from baseline in Body Mass Index (BMI) | From enrolment until up to at least 3 years | BMI will be derived based on weight and height at every study visit |
Countries
Belgium, Czechia, Greece, Ireland, Israel, Netherlands, New Zealand, Spain, United Kingdom
Outcome results
None listed